| 1. |
|
|
| 2. |
|
|
| 3. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 4. |
- Sandström, Agneta, 1959-, et al.
(författare)
-
Cognitive deficits in relation to personality type and hypothalamic-pituitary-adrenal (HPA) axis dysfunction in women with stress-related exhaustion
- 2011
-
Ingår i: Scandinavian Journal of Psychology. - Oxford : Wiley-Blackwell. - 0036-5564 .- 1467-9450. ; 52:1, s. 71-82
-
Tidskriftsartikel (refereegranskat)abstract
- Exhaustion caused by long-term work-related stress may cause cognitive dysfunction. We explored factors that may link chronic stress and cognitive impairment. Personality, psychiatric screening, and behavior were assessed by self-reporting measures in 20 female patients (mean age 39.3 years; range 26–53) with a preliminary diagnosis of stress-related exhaustion and in 16 healthy matched controls. Cognitive performance was investigated with a detailed neuropsychological test battery. Cortisol axis function was assessed by urinary and saliva collections of cortisol, dexamethasone suppression, Synacthen response, and corticotropin-releasing hormone (CRH) tests. Proinflammatory cytokines were measured. Hippocampal volumes were estimated by magnetic resonance imaging. Multivariate and univariate statistical methods were used to explore putative differences between groups and factors linked to cognitive impairment. Cognitive function clearly differed between groups, with decreased attention and visuospatial memory in the patient group, suggesting frontal cortex/medial temporal cortex-network dysfunction. Increased harm avoidance and persistence was present among patients, with lowered self-directedness linked to lower quality of life, increased anxious and depressive tendencies, and experiences of psychosocial stress. Attention was decreased with concomitantly impaired visuospatial memory. The pituitary (adrenocorticotropic hormone, ACTH) response to CRH was decreased in patients, with an increased cortisol/ACTH response to CRH. However, cortisol production rates, diurnal or dexamethasone-suppressed saliva cortisol levels, and the cortisol response to Synacthen were unaltered. Hippocampal volumes did not differ between groups. These findings suggest that cognitive dysfunction in stress-related exhaustion is linked to distinct personality traits, low quality of life, and a decreased ACTH response to CRH.
|
|
| 5. |
- Sandström, Monica, 1946-, et al.
(författare)
-
External power frequency magnetic field-induced jitter on computer monitors
- 1993
-
Ingår i: Behaviour & Information Technology. - : Taylor & Francis. - 0144-929X .- 1362-3001. ; 12:6, s. 359-363
-
Tidskriftsartikel (refereegranskat)abstract
- Power frequency magnetic fields with flux densities greater than 0.5 μT are not uncommon in offices. This level has been shown to induce jitter on VDT monitors. In the present project, these magnetic field-induced disturbances have been studied in the laboratory in order to establish a firm technical basis for future studies of the disturbance's influence on eye strain in VDT workers. Eight volunteers judged the occurrence of distortion when an applied external magnetic field was varied both in amplitude and frequency for 8 investigated VDT screens. The level of the external 50 Hz magnetic field when the distortion was detectable ranged from 0.6 to 1.1 μT. If the screen was viewed through a stereomicroscope (25 × magnification), the corresponding level was in the order of 0.2 μT. If the frequency difference between the external magnetic field and the refresh rate of the screen is only ±1-2 Hz, the disturbance is noticeable at even lower flux densities.
|
|
| 6. |
- Ahlgren, Sara, et al.
(författare)
-
Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules
- 2008
-
Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 19:1, s. 235-243
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i.
|
|
| 7. |
- Ahlgren, Sara, et al.
(författare)
-
Targeting of HER2-Expressing Tumors Using 111In-ABY-025, a Second-Generation Affibody Molecule with a Fundamentally Reengineered Scaffold
- 2010
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 51:7, s. 1131-1138
-
Tidskriftsartikel (refereegranskat)abstract
- Overexpression of HER2 in breast carcinomas predicts response to trastuzumab therapy. Affibody molecules based on a non-immunoglobulin scaffold have demon-strated high potential for in vivo molecular imaging of HER2-expressing tumors. Re-engineering of the molecular scaffold has led to a second generation of optimized Affibody molecules, having a surface distinctly different from the parental protein domain from staphylococcal protein A. The new tracer showed further increased melting point, stability and overall hydrophilicity compared to the parental molecule, and was shown to be more amenable for chemical peptide synthesis. The goal of this study was to assess potential effects of this extensive re-engineering on HER2 targeting, using ABY-025, a DOTA conjugated variant of the novel tracer. Methods: 111In-ABY-025 was compared with previously evaluated parent HER2-binding Affibody tracers in vitro and in vivo. The in vivo behavior was further evaluated in mice bearing SKOV-3 xenografts, in rats and in cynomolgus macaques. Results: 111In-ABY-025 bound specifically to HER2 in vitro and in vivo. Direct comparison with the previous generation of HER2-binding tracers showed that ABY-025 retained excellent targeting properties. Rapid blood clearance was shown in mice, rats and macaques. A highly specific tumor uptake of 16.7 ± 2.5 %IA/g was seen at 4 h after injection. The tumor-to-blood ratio was 6.3 at 0.5 h, 88 at 4 h, and increased up to 3 days after injection. Gamma camera imaging of tumors was already possible 0.5 h after injection. Furthermore, repeated i.v. administration of ABY-025 did not induce antibody formation in rats. Conclusions: The biodistribution of 111In-ABY-025 was in remarkably good agreement with the parent tracers, despite profound re-engineering of the non-binding surface. The molecule displayed rapid blood clearance in all species investigated and excellent targeting capacity in tumor bearing mice, leading to high tumor-to-organ-ratios and high contrast imaging shortly after injection.
|
|
| 8. |
|
|
| 9. |
- Altai, Mohamed, et al.
(författare)
-
188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
- 2014
-
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:11, s. 8-1842
-
Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate (188)Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors.METHODS: ZHER2:V2 was labeled with (188)Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment.RESULTS: Binding of (188)Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that (188)Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible.CONCLUSION: (188)Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
|
|
| 10. |
|
|
| 11. |
- Altai, Mohamed, et al.
(författare)
-
Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA
- 2012
-
Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:4, s. 518-529
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.
|
|
| 12. |
- Altai, Mohamed, et al.
(författare)
-
Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re.
- 2014
-
Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 87, s. 519-28
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
|
|
| 13. |
- Altai, Mohamed, et al.
(författare)
-
Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with 188-Re
- 2013
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:Suppl. 2, s. S219-S220
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1±0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172±32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
|
|
| 14. |
|
|
| 15. |
- Andersson, Ken G, et al.
(författare)
-
Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors
- 2015
-
Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 34:2, s. 1042-8
-
Tidskriftsartikel (refereegranskat)abstract
- Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium‑111 (111In) and assessed invitro and invivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with 111In provided stable conjugates. Invitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT‑474 breast carcinoma cells. In mice bearing BT‑474 xenografts, the tumor uptake of the two conjugates was receptor‑specific. Direct invivo comparison of 111In-HEHEHE-Z08698-NOTA and 111In-HEHEHE-Z08699‑NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for 111In-HEHEHE-Z08698-NOTA [12±3 vs. 8±1, 4h post injection (p.i.)] due to more efficient blood clearance. 111In-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.
|
|
| 16. |
- Andersson, Mattias, et al.
(författare)
-
Editor's Choice – Structured Computed Tomography Analysis can Identify the Majority of Patients at Risk of Post-Endovascular Aortic Repair Rupture
- 2022
-
Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 64, s. 166-174
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The main objective was to report mechanisms and precursors for post-endovascular aneurysm repair (EVAR) rupture. The second was to apply a structured protocol to explore whether these factors were identifiable on follow up computed tomography (CT) prior to rupture. The third objective was to study the incidence, treatment, and outcome of post-EVAR rupture. Methods: This was a multicentre, retrospective study of patients treated with standard EVAR at five Swedish hospitals from 2008 to 2018. Patients were identified from the Swedvasc registry. Medical records were reviewed up to 2020. Index EVAR and follow up data were recorded. The primary endpoint was post-EVAR rupture. CT at follow up and at post-EVAR rupture were studied, using a structured protocol, to determine rupture mechanisms and identifiable precursors. Results: In 1 805 patients treated by EVAR, 45 post-EVAR ruptures occurred in 43 patients. The cumulative incidence was 2.5% over a mean follow up of 5.2 years. The incidence rate was 4.5/1 000 person years. Median time to post-EVAR rupture was 4.1 years. A further six cases of post-EVAR rupture in five patients found outside the main cohort were included in the analysis of rupture mechanisms only. The rupture mechanism was type IA in 20 of 51 cases (39%), IB in 20 of 51 (39%) and IIIA/B in 11 of 51 (22%). One of these had type IA + IB combined. One patient had an aortoduodenal fistula without another mechanism being identified. Precursors had been noted on CT follow up prior to post-EVAR rupture in 16 of 51 (31%). Retrospectively, using the structured protocol, precursors could be identified in 43 of 51 (84%). In 17 of 27 (63%) cases missed on follow up but retrospectively identifiable, the mechanisms were type IB/III. Overall, the 30 day mortality rate after post-EVAR rupture was 47% (n = 24/51) and the post-operative mortality rate was 21% (n = 7/33). Conclusions: Most precursors of post-EVAR rupture are underdiagnosed but identifiable before rupture using a structured follow up CT protocol. Precursors of type IB and III failures caused the majority of post-EVAR ruptures.
|
|
| 17. |
- Andersson, Magnus, et al.
(författare)
-
Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
|
|
| 18. |
- Andersson, Åsa, et al.
(författare)
-
Patient involvement in surgical care-Healthcare personnel views and behaviour regarding patient involvement
- 2021
-
Ingår i: Scandinavian Journal of Caring Sciences. - : WILEY. - 0283-9318 .- 1471-6712. ; 35:1, s. 96-103
-
Tidskriftsartikel (refereegranskat)abstract
- Background All professions in surgical care have a responsibility to include patients in their health care. By Swedish law, all care should be done in dialogue with the patient. The essential part of health care is the meeting between patient and healthcare professional. In the interaction, a decision can be made, and needs can be identified to a safer care. Previous studies on patient participation have focussed on patients perspectives in surgical care, but there is a paucity of studies about the personnels perspective of estimated patient involvement in surgical care. Aim The aim of this study was to identify and describe healthcare personnels view and behaviour regarding patient involvement in surgical care. Method A quantitative study with various professions was conducted. A validated questionnaire was used, remaining questions grouped under following areas: patient involvement, acute phase, hospital time, discharge phase and questions on employment and workplace. Results A total of 140 questionnaires were sent out to a surgical clinic in Sweden, and 102 questionnaires were answered. All professionals stated that clear information is an important part of patient involvement in surgical care. Statistically significant differences existed between the professions in the subscale information. Physicians rated their information higher than the Registered Nurses (p = 0.005) and the practical nurses did (p = 0.001). Hindrances to involving patients were lack of time and other priority tasks. Conclusions Professionals in surgical care graded information to be the most important thing for patient involvement. Participation in important decisions, including the possibility to express personal views and ask questions, is important factors for patient involvement. Barriers against patient involvement are lack of time and prioritisation of other work activities.
|
|
| 19. |
- Axelson, Mattias, et al.
(författare)
-
Collective action problems in public sector innovation: A business model perspective
- 2017
-
Ingår i: Creativity and Innovation Management. - : Wiley. - 0963-1690 .- 1467-8691. ; 26:4, s. 370-378
-
Tidskriftsartikel (refereegranskat)abstract
- We explore how the literature on business models can explain the outcomes of innovation attempts in the public sector. Our findings suggest that governments can access a well-developed knowledge domain for a public sector area but have a weak ability to propagate its value for society. Drawing on the business model literature concerning interdependence and distributed agency, we illustrate how a collective action problem related to innovation may arise in the public sector. We illustrate this new category of public innovation challenge with the (failed) case of the Swedish civil contingencies system and subsequently discuss a new line of inquiry for future research.
|
|
| 20. |
- Borges, João Batista, et al.
(författare)
-
Regional Lung Perfusion estimated by Electrical Impedance Tomography in a piglet model of lung collapse
- 2011
-
Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 112:1, s. 225-236
-
Tidskriftsartikel (refereegranskat)abstract
- The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology which provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT) based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6 %, with a standard deviation of 2.9 %. This method outperformed the estimates of lung perfusion based on impedance-pulsatility. In conclusion, we describe a novel method based on Electrical Impedance Tomography for estimating regional lung perfusion at the bedside. In both, healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this paper has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.
|
|
| 21. |
- Borges, João Batista, et al.
(författare)
-
Ventilation Distribution Studies Comparing Technegas and "Gallgas" Using (GaCl3)-Ga-68 as the Label
- 2011
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 52:2, s. 206-209
-
Tidskriftsartikel (refereegranskat)abstract
- Ventilation distribution can be assessed by SPECT with Technegas. This study was undertaken in piglets with different degrees of ventilation inhomogeneity to compare PET using Ga-68-labeled pseudogas or "Gallgas" with Technegas. Methods: Twelve piglets were studied in 3 groups: control, lobar obstruction, and diffuse airway obstruction. Two more piglets were assessed for lung volume (functional residual capacity). Results: In controls, SPECT and PET images showed an even distribution of radioactivity. With lobar obstruction, the absence of ventilation of the obstructed lobe was visible with both techniques. In diffuse airway obstruction, SPECT images showed an even distribution of radioactivity, and PET images showed more varied radioactivity over the lung. Conclusion: PET provides detailed ventilation distribution images and a better appreciation of ventilation heterogeneity. Gallgas with PET is a promising new diagnostic tool for the assessment of ventilation distribution.
|
|
| 22. |
- Bragina, Olga, et al.
(författare)
-
Phase I study of 99mTc-ADAPT6, a scaffold protein-based probe for visualization of HER2 expression in breast cancer
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first in-human study was to evaluate biodistribution, dosimetry, and safety of HER2-specific 99mTc-ADAPT6.METHODS. Twenty-two patients with HER2-positive (n=11) or HER2-negative (n=11) primary breast cancer were intravenously injected with 385125 MBq. The injected amount of protein was either 500 μg (n=11) or 1000 μg (n=11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort received a dose of 250 μg, and the planar scintigraphy followed by SPECT imaging was performed after 2 h only.RESULTS. Injection of 99mTc-ADAPT6 was well tolerated for all doses evaluated in the study, and was not associated with any adverse effects. 99mTc-ADAPT6 cleared rapidly from the blood and the majority of tissues. The normal organs with the highest accumulation were kidney, liver and lung. The effective doses were determined to 0.0090.002 and 0.0100.003 mSv/MBq when injecting protein amounts of 500 and 1000 μg, respectively. Injection of 500 μg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 3719 vs 52, p < 0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p < 0.5) higher for the injected mass of 500 μg than for both 250 and 1000 μg. In one patient, the imaging using 99mTc-ADAPT6 revealed three bone metastases, which were not found at the time of diagnosis by CT or 99mTcpyrophosphate bone scan. MRI imaging confirmed this finding.CONCLUSION. Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. A protein dose of 500 μg is preferable for discrimination between tumors with high and low expression of HER2. 99mTc-ADAPT6 is a promising imaging probe for the stratification of patients for HER2-targeting therapy.
|
|
| 23. |
- Bragina, Olga, et al.
(författare)
-
Phase I study of 99mTc-ADAPT6, a scaffold protein-based probe for visualization of HER2 expression in breast cancer
- 2021
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:4, s. 493-499
-
Tidskriftsartikel (refereegranskat)abstract
- Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6.METHODS: Twenty-nine patients with primary breast cancerwere included. In 22 patients with HER2-positive (n = 11) or HER2-negative (n = 11) histopathology an intravenous injection with 385±125 MBq 99mTc-ADAPT6 was performed, randomized to an injected protein mass of either 500 µg (n = 11) or 1000 µg (n = 11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort (n = 7) was injected with 165±29 MBq (injected protein mass 250 µg) and imaging was performed after 2 h only.RESULTS: Injections of 99mTc-ADAPT6 at all injected mass levels were well tolerated and not associated with adverse effects. 99mTc-ADAPT6 cleared rapidly from blood and most other tissues. The normal organs with the highest accumulation were kidney, liver and lung. Effective doses were 0.009±0.002 and 0.010±0.003 mSv/MBq for injected protein masses of 500 and 1000 µg, respectively. Injection of 500 µg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 37±19 vs 5±2, p<0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p<0.05) higher for injected mass of 500 µg than for both 250 and 1000 µg.CONCLUSION: Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. Protein dose of 500 µg is preferable for discrimination between tumors with high and low expression of HER2. Further studies are justified to evaluate if 99mTc-ADAPT6 can be used as an imaging probe for stratification of patients for HER2-targeting therapy in the areas where PET imaging is not readily available.
|
|
| 24. |
- Broström (red), Tor, et al.
(författare)
-
Brandsäkerhet för byggnader med kulturvärden: En kunskapsöversikt
- 2021
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Abstract [sv] Arbetet med brandsäkerhet för byggnader med kulturvärden kräver anpassade lösningar som också kan tillgodose ett bevarande av byggnaderna och deras kulturvärden. Det finns, utspritt, mycket kunskap och erfarenhet inom det här området både i Sverige och internationellt. För att tillgodose ett behov av samlad kunskap inom detta område initierade Brandforsk en kunskapsöversikt tillsammans med Akademiska hus, Fortifikationsverket, Kammarkollegiet, Kyrkans försäkring, Riksantikvarieämbetet och Statens fastighetsverk. Den här kunskapsöversikten syftar till att sammanställa och presentera den kunskap som finns. Ett kompletterande syfte är att definiera områden där kunskap saknas. Kunskapsöversikten är indelad i sex områden: 2. Skydd mot brands uppkomst 3. Spridning av brand inom byggnad 4. Spridning av brand till byggnad 5. Brandens påverkan på byggnadens stomme 6. Utrymning 7. Räddningstjänstens insats Med utgångspunkt från workshops har en sammanställning av behovsbilden gjorts. Kunskapsöversikten och behovsbilden ligger till grund för en gap-analys vilken pekar på behov av fortsatt forskning och utveckling. Abstract [en] Working with fire safety in historic buildings requires adapted solutions that can also satisfy the preservation of the buildings and their cultural values. There is a lot of knowledge and experience in this area both in Sweden and internationally. In order to make this available to end users, Brandforsk initiated a literature review together with a group of national sponsors. This literature review aims to compile and present the documented knowledge in the field. A complementary purpose is to define knowledge gaps. The review is divided into six areas: 2. Fire prevention 3. Fire spread within buildings 4. Fire spread between structures 5. Structural fire resistance 6. Evacuation 7. Fire and rescue service activities Based on workshops the needs of end users have been compiled. A comparison of the outcome of the review and the end user needs defines a knowledge gap pointing to the need for continued research and development.
|
|
| 25. |
- De Brandt, Jana, 1991-, et al.
(författare)
-
The Borg Cycle Strength Test (BCST) for prescribing supramaximal high-intensity interval training (HIIT) in COPD
- 2023
-
Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 62:Supplement 67
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Prescription of supramaximal HIIT is ideally based on an all-out test. This is, however, not suitable for people with COPD, leading to the use of workloads obtained during a maximal incremental test (CPET), which are less specific for the prescription of supramaximal HIIT. Hence, we evaluated the feasibility of a submaximal anaerobic test, the BCST, that has been used in older adults to prescribe supramaximal HIIT, and the anaerobic cycle capacity of people with COPD vs. matched healthy controls (HC).Methods: Sixteen persons with COPD and HC performed a CPET and a BCST. The BCST is an incremental stepwise test (30s cycling, 30s rest) with two end-of-test criteria: 1) Rating of perceived exertion (RPE) ≥17 or 2) cadence <75 RPM for >5s. End-of-test RPE, symptoms, peak workload (Wpeak) and cardiorespiratory demand were obtained to assess feasibility.Results: A higher Wpeak and lower RPE, symptoms and cardiorespiratory demand were observed in the BCST vs. CPET in both groups (Table1). Absolute BCST Wpeak was significantly lower, while relative BCST Wpeak (%Wpeak CPET) was similar in people with COPD (146±24%) vs. HC (157±17%)(P=0.114).Conclusion: In people with COPD, the BCST is a feasible short-duration submaximal anaerobic test specific for prescribing supramaximal HIIT. Compared to the CPET, it allows for higher workloads with lower cardiorespiratory demand and symptom burden.
|
|
| 26. |
|
|
| 27. |
- Ebeling Barbier, Charlotte, et al.
(författare)
-
Selective internal radiation therapy in patients with progressive neuroendocrine liver metastases
- 2016
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 43:8, s. 1425-1431
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the safety and efficacy of selective internal radiation therapy (SIRT) in patients with unresectable liver metastases from neuroendocrine tumours (NETLMs).METHODS: This retrospective study included 40 patients with progressive NETLMs (22 women, 18 men, mean age 61.6 years) who underwent SIRT with (90)Y-labelled resin microspheres. Tumour response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) on CT or MR images. Medical records were reviewed.RESULTS: In the 40 patients, 54 evaluable SIRT procedures were performed, 33 to the right liver lobe (mean activity 1.31 GBq), 13 to the left lobe (mean activity 0.85 GBq), and 8 to both lobes (mean activity 1.61 GBq). Late follow-up imaging (mean 20 months) was performed after 44 of the treatments. Objective tumour response and disease control rates were 54 % (29 of 54 treatments) and 94 % (51 treatments), respectively, at the early follow-up examination (mean 3 months) and 34 % (15 treatments) and 57 % (25 treatments), respectively at the late follow-up examination. Mean overall survival from the first SIRT was 34,8 months and survival rates at 1, 2, 3 and 5 years were 76 %, 59 %, 52 % and 35 % respectively. Adverse effects were generally mild and easily manageable, except in one patient who died from radiation-induced liver failure. Of the 45 patients, 18 (45 %) had received peptide receptor radionuclide therapy (PRRT) prior to SIRT.CONCLUSION: SIRT with (90)Y-labelled resin microspheres is a safe and effective treatment for patients with progressive NETLM, and also for those who have received prior PRRT.
|
|
| 28. |
- Eriksson, Maria, et al.
(författare)
-
Improved treatment of glioblastoma : changes in survival over two decades at a single regional Centre
- 2019
-
Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 58:3, s. 334-341
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Glioblastoma (GBM) is an aggressive brain tumor with a short overall survival (OS) in general. The treatment of GBM has evolved over the last decades and is today multimodal including surgical resection followed by radiochemotherapy and adjuvant chemotherapy for patients in good performance status. The aim of this study was to evaluate the development of treatment and the outcome for GBM patients at a single regional center.Patients and methods: Survival was studied for 571 patients in our region diagnosed with GBM between 1995 and 2015. Samples from 244 patients out of those treated 2005-2015 have been included in a tissue/blood bank and a clinical database has been set up with basic patient characteristics and details on surgery and non-surgical treatment.Results: The median OS for all patients from 1995 to 2015 was 9.3 months. There was a stepwise improvement from 6.9 to 10.3 months for patients diagnosed 1995-1996 and 2010-2015, respectively (p<.05). The 2-year survival for the same time periods improved from 7% to 18% (p<.01). After introduction of postoperative radiochemotherapy for patients in good performance status in 2005 an increased OS was noted and following implementation of intraoperative 5-aminolevulinic acid the number of tumor resection 95% did increase from 33% to 54% (p<.001). Positive prognostic factors for survival were young age, good performance status, absence of inflammatory disease, absence of diabetes or metabolic disease, tumor resection 95%, and completion of postoperative radiochemotherapy.Discussion: The results of this study are consistent with earlier results regarding survival and prognostic factors and confirm results from randomized controlled trials in a clinical setting. Despite the improvements made, the prognosis is still dismal and the need for further research on GBM treatment is great.
|
|
| 29. |
- Freedman, Nanette, et al.
(författare)
-
Personalized radiation dosimetry for PRRT : how many scans are really required?
- 2020
-
Ingår i: EJNMMI Physics. - : Springer Science and Business Media LLC. - 2197-7364. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeOver recent years, peptide receptor radiotherapy (PRRT) has been recognized as an effective treatment for patients with metastatic neuroendocrine tumors (NETs). Personalized dosimetry can contribute to improve the outcome of peptide receptor radiotherapy (PRRT) in patients with metastatic NETs. Dosimetry can aid treatment planning, ensuring that absorbed dose to vulnerable normal organs (kidneys and bone marrow) does not exceed safe limits over serial treatments, and that absorbed dose to tumor is sufficient. Absorbed dose is estimated from a series of post-treatment SPECT/CT images. Total self-dose is proportional to the integral under the time activity concentration curve (TACC). Method dependence of image-based absorbed dose calculations has been previously investigated, and we set out here to extend previous work by examining implications of number of data points in the TACC and the numerical integration methods used in estimating absorbed dose.MethodsIn this retrospective study, absorbed dose estimates and effective half-lives were calculated by fitting curves to TACCs for normal organs and tumors in 30 consecutive patients who underwent a series of 4 post-treatment SPECT/CT scans at 4 h, 24 h, 4–5 days, and 1 week following 177Lu-DOTATATE PRRT. We examined the effects of including only 2 or 3 rather than all 4 data points in the TACC, and the effect of numerical integration method (mono-exponential alone or in combination with trapezoidal rule) on the absorbed dose and half-life estimates. Our current method is the combination of trapezoidal rule over the first 24 h, with mono-exponential fit thereafter extrapolated to infinity. The other methods were compared to this current method.ResultsDifferences in absorbed dose and effective half-life between the current method and estimates based only on the second, third, and fourth scans were very small (mean differences < 2.5%), whereas differences between the current method and 4-point mono-exponential fit were higher (mean differences < 5%) with a larger range. It appears that in a 4-point mono-exponential fit the early (4 h) time point may skew results, causing some large errors. Differences between the current method and values based on only 2 time points were relatively small (mean differences < 3.5%) when the 24 h and 1 week scans were used, but when the 24 h and 4–5 days scans, or the 4–5 days and 1 week scans were used, differences were greater.ConclusionThis study indicates that for 177Lu-DOTATATE PRRT, accurate estimates of absorbed dose for organs and tumors may be estimated from scans at 24 h, 72 h, and 1 week post-treatment without an earlier scan. It may even be possible to cut out the 72 h scan, though the uncertainty increases. However, further work on more patients is required to validate this.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Frykholm, Erik, 1985-, et al.
(författare)
-
Applicability of a supramaximal high-intensity interval training program for older adults previously not engaged in regular exercise : analyses of secondary outcomes from the Umeå HIT Study
- 2024
-
Ingår i: Psychology of Sport And Exercise. - : Elsevier. - 1469-0292 .- 1878-5476. ; 73
-
Tidskriftsartikel (refereegranskat)abstract
- This analysis of secondary outcomes investigated the applicability of supramaximal high-intensity interval training (HIT) with individually prescribed external intensity performed on stationary bicycles. Sixty-eight participants with a median (min; max) age of 69 (66; 79), at the time not engaged in regular exercise were randomized to 25 twice-weekly sessions of supramaximal HIT (20-min session with 10 × 6-s intervals) or moderate-intensity training (MIT, 40-min session with 3 × 8-min intervals). The primary aim was outcomes on applicability regarding; adherence to prescribed external interval intensity, participant reported positive and negative events, ratings of perceived exertion (RPE 6–20), and affective state (Feeling Scale, FS -5–5). A secondary aim was to investigate change in exercise-related self-efficacy (Exercise Self-Efficacy Scale) and motivation (Behavioural Regulations in Exercise Questionnaire-2). Total adherence to the prescribed external interval intensity was [median (min; max)] 89 % (56; 100 %) in supramaximal HIT, and 100 % (95; 100 %) in MIT. The supramaximal HIT group reported 60 % of the positive (112 of 186) and 36 % of the negative (52 of 146) events. At the end of the training period, the median (min; max) session RPE was 15 (12; 17) for supramaximal HIT and 14 (9; 15) for MIT. As for FS, the median last within-session rating was 3 (−1; 5) for supramaximal HIT and 3 (1; 5) for MIT. Exercise-related motivation increased (mean difference in Relative Autonomy Index score = 1.54, 95 % CI [0.69; 2.40]), while self-efficacy did not change (mean difference = 0.55, 95 % CI [-0.75; 1.82]), regardless of group. This study provide support for supramaximal HIT in supervised group settings for older adults.
|
|
| 33. |
- Fröss-Baron, Katarzyna, et al.
(författare)
-
177Lu-DOTATATE Therapy of Advanced Pancreatic Neuroendocrine Tumors Heavily Pretreated With Chemotherapy : Analysis of Outcome, Safety and Their Determinants
- 2021
-
Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:4, s. 330-343
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To retrospectively analyze toxicity, progression-free survival (PFS), overall survival (OS) and their determinants in patients with advanced pancreatic neuroendocrine tumors (panNETs), previously pretreated with chemotherapy, undergoing peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE.Methods: In total, 102 patients with advanced panNETs, previously pretreated with one (67%) or several (33%) lines of chemotherapy were included, of whom 90 % had progressive disease and the majority (74.5%) with grade 2 tumors. 177Lu-DOTATATE, 7.4 GBq per cycle, was administered with 6 to 8 weeks interval, in 88 % of patients utilizing a dosimetry-guided protocol, until an absorbed dose of 23 Gy to the kidneys was reached.Results: Mean 32±10.9 GBq per patient was administered in 1-10 cycles starting median 36 months after panNET diagnosis. Median follow-up was 34 months. Median PFS was 24 months and median OS was 42 months from start of PRRT. Independent risk factors for both progression and death were liver tumor burden >50%, more than one line of previous chemotherapy and elevated alkaline phosphatase (ALP). Resection of the primary tumor was linked to longer survival. Bone marrow toxicity grade 3-4 occurred in 10.8%. One patient (1.0 %) developed acute myeloid leukemia. Bone marrow toxicity was unrelated to type and length of previous chemotherapy, amount of administered activity and absorbed dose to the bone marrow.Conclusion: 177Lu-DOTATATE therapy was feasible, highly effective and safe in patients with advanced panNETs heavily pretreated with chemotherapy. More than one line of chemotherapy was a therapy related independent risk factor for shorter PFS and OS.
|
|
| 34. |
- Garousi, Javad, et al.
(författare)
-
ADAPT, a Novel Scaffold Protein-Based Probe for Radionuclide Imaging of Molecular Targets That Are Expressed in Disseminated Cancers
- 2015
-
Ingår i: Cancer Research. - : American Association for Cancer Research Inc.. - 0008-5472 .- 1538-7445. ; 75:20, s. 4364-4371
-
Tidskriftsartikel (refereegranskat)abstract
- Small engineered scaffold proteins have attracted attention as probes for radionuclide-based molecular imaging. One class of these imaging probes, termed ABD-Derived Affinity Proteins (ADAPT), has been created using the albumin-binding domain (ABD) of streptococcal protein G as a stable protein scaffold. In this study, we report the development of a clinical lead probe termed ADAPT6 that binds HER2, an oncoprotein overexpressed in many breast cancers that serves as a theranostic biomarker for several approved targeting therapies. Surface-exposed amino acids of ABD were randomized to create a combinatorial library enabling selection of high-affinity binders to various proteins. Furthermore, ABD was engineered to enable rapid purification, to eradicate its binding to albumin, and to enable rapid blood clearance. Incorporation of a unique cysteine allowed site-specific conjugation to a maleimido derivative of a DOTA chelator, enabling radionuclide labeling, In-111 for SPECT imaging and Ga-68 for PET imaging. Pharmacologic studies in mice demonstrated that the fully engineered molecule In-111/Ga-68-DOTA(HE) 3-ADAPT6 was specifically bound and taken up by HER2-expressing tumors, with a high tumor-to-normal tissue ratio in xenograft models of human cancer. Unbound tracer underwent rapid renal clearance followed by high renal reabsorption. HER2-expressing xenografts were visualized by gamma-camera or PET at 1 hour after infusion. PET experiments demonstrated feasibility for discrimination of xenografts with high or low HER2 expression. Our results offer a preclinical proof of concept for the use of ADAPT probes for noninvasive in vivo imaging.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Garske, Ulrike, et al.
(författare)
-
Lessons on Tumour Response : Imaging during Therapy with Lu-177-DOTA-octreotate. A Case Report on a Patient with a Large Volume of Poorly Differentiated Neuroendocrine Carcinoma
- 2012
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 2:5, s. 459-471
-
Tidskriftsartikel (refereegranskat)abstract
- Favourable outcomes of peptide receptor radiotherapy (PRRT) of neuroendocrine tumours have been reported during the last years. Still, there are uncertainties on the radionuclides to be used, the treatment planning, and the indication in patients with a high proliferation rate. This case report describes a patient with a high tumour burden of poorly differentiated neuroendocrine carcinoma of unknown primary with a proliferation rate in liver metastases up to 50%, undergoing fractionated treatment with 7 cycles of Lu-177-DOTA-octreotate (7.4 GBq each) after disease progression on two different chemotherapy regiments. Based on initial staging scintigraphy, somatostatin receptor expression was very high. Longitudinal dosimetry studies during therapy indicated ongoing increases in tumour-to-organ ratios that coincided with an objective response. We conclude that fractionated therapy with Lu-177-DOTA-octreotate should be considered a treatment option also for those patients with large tumours, high proliferation, and high receptor expression.
|
|
| 38. |
- Garske, Ulrike, et al.
(författare)
-
Minor changes in effective half-life during fractionated 177Lu-Octreotate therapy
- 2011
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:1, s. 86-96
-
Tidskriftsartikel (refereegranskat)abstract
- Fractionated (177)Lu-DOTA-octreotate therapy has been reported to be an effective treatment option for patients with generalized neuroendocrine tumors. In our clinic, full individual dosimetry is performed during the first therapy cycle, while dosimetry at later cycles is based on the 24 h uptake measurement assuming an unchanged effective half-life. Our aim was to evaluate this assumption and the variation in the 24 h uptake during therapy. Patients. Thirty patients, 13 women and 17 men, were included in the study. Methods. During the first therapy cycle the (177)Lu-concentration was measured with SPECT/CT over the abdomen at 24 h, 96 h and 168 h after infusion. The effective half-life was determined for the kidneys, liver and spleen. The procedure was repeated at cycle 4 or 5. Results. The median ratio between the effective half-lives of the latter and the first cycle was 0.97 and 1.01 for the right and left kidney, with a range of 0.89-1.01 (1st-3rd quartile) and 0.93-1.05, respectively. Discussion. The mean value of the ratios was slightly lower than one, indicating a tendency towards increased activity elimination during therapy. In individual patients, significant changes were found for all organs, often when a large tumor burden reduction occurred during treatment. Possible contributing factors appeared to be larger amounts of non-tumor bound tracer, improved organ function (kidneys), decrease of vessel obstruction (spleen), less scatter from large tumors and reduction of small metastases (liver and spleen). Conclusion. With most patients it is safe to estimate absorbed doses to kidneys, liver and spleen from 24 h activity concentration assuming an unchanged effective half-life during therapy. Patients with risk factors for kidney dysfunction need to be monitored in more detail. Simplified dosimetry based on the assumption of unchanged effective half-life can function as guidance to the number of therapy cycles an individual patient can tolerate.
|
|
| 39. |
- Garske, Ulrike, 1963-, et al.
(författare)
-
Prospective observational study of 177Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs) : feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity
- 2018
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 45:6, s. 970-988
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Peptide receptor radionuclide therapy in patients with neuroendocrine tumours has yielded promising results. This prospective study investigated the feasibility of dosimetry of the kidneys and bone marrow during therapy and its impact on efficacy and outcome.METHODS: Lu-DOTA-octreotate with co-infusion of a mixed amino acid solution, and cycles were repeated until the absorbed dose to the kidneys reached 23 Gy or there were other reasons for stopping therapy. The Ki-67 index was ≤2% in 47 patients (23.5%), 3-20% in 121 (60.5%) and >20% in 16 (8%).RESULTS: In 123 patients (61.5%) the absorbed dose to the kidneys reached 23 Gy with three to nine cycles during first-line therapy; in no patient was a dose to the bone marrow of 2 Gy reached. The best responses (according to RECIST 1.1) were a complete response (CR) in 1 patient (0.5%), a partial response (PR) in 47 (23.5%), stable disease (SD) in 135 (67.5%) and progressive disease (PD) in 7 (3.5%). Median progression-free survival was 27 months (95% CI 22-30 months) in all patients, 33 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 15 months in those in whom it did not. Median overall survival (OS) was 43 months (95% CI 39-53 months) in all patients, 54 months in those in whom the absorbed dose to the kidneys reached 23 Gy and 25 months in those in whom it did not. Median OS was 60 months in patients with a best response of PR or CR, 42 months in those with SD and 16 months in those with PD. Three patients (1.5%) developed acute leukaemia, 1 patient (0.5%) chronic leukaemia (unconfirmed) and 30 patients (15%) grade 3 or 4 bone marrow toxicity. Eight patients (4%) developed grade 2 kidney toxicity and one patient (0.5%) grade 4 kidney toxicity.CONCLUSIONS: Lu-DOTA-octreotate is feasible. Patients in whom the absorbed dose to the kidneys reached 23 Gy had a longer OS than those in whom it did not. Patients with CR/PR had a longer OS than those with SD. Bone marrow dosimetry did not predict toxicity.
|
|
| 40. |
- Gear, Jonathan, et al.
(författare)
-
EANM enabling guide : how to improve the accessibility of clinical dosimetry
- 2023
-
Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 50, s. 1861-1868
-
Tidskriftsartikel (refereegranskat)abstract
- Dosimetry can be a useful tool for personalization of molecular radiotherapy (MRT) procedures, enabling the continuous development of theranostic concepts. However, the additional resource requirements are often seen as a barrier to implementation. This guide discusses the requirements for dosimetry and demonstrates how a dosimetry regimen can be tailored to the available facilities of a centre. The aim is to help centres wishing to initiate a dosimetry service but may not have the experience or resources of some of the more established therapy and dosimetry centres. The multidisciplinary approach and different personnel requirements are discussed and key equipment reviewed example protocols demonstrating these factors are given in the supplementary material for the main therapies carried out in nuclear medicine, including [I-131]-NaI for benign thyroid disorders, [Lu-177]-DOTATATE and I-131-mIBG for neuroendocrine tumours and [Y-90]-microspheres for unresectable hepatic carcinoma.
|
|
| 41. |
- Gruneau, Lina, et al.
(författare)
-
Cost-effectiveness analysis of noninvasive tests to identify advanced fibrosis in non-alcoholic fatty liver disease
- 2023
-
Ingår i: HEPATOLOGY COMMUNICATIONS. - : LIPPINCOTT WILLIAMS & WILKINS. - 2471-254X. ; 7:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Advanced fibrosis is associated with end-stage liver disease (ESLD) and mortality in NAFLD. As treatments specifically targeted at NAFLD are lacking, patient management focuses on surveillance for early detection of complications related to end-stage liver disease. Although current and emerging diagnostic tools for the detection of advanced fibrosis are crucial for surveillance, their added value is unclear. The aim of this study was to evaluate the costs and health outcomes of noninvasive tests in patient management strategies for diagnosing advanced fibrosis in NAFLD patients. Method: A decision analytical model was developed to evaluate 13 patient management strategies, including a no-testing strategy and 12 diagnostic algorithms with noninvasive tests (fibrosis 4-score, enhanced liver fibrosis, vibration controlled transient elastography), and liver biopsy. Model inputs were synthesized from the literature and Swedish registries. Lifetime health care costs, life years, quality-adjusted life years, clinical outcomes, and incremental cost-effectiveness ratios were calculated for a cohort of 55-year-old patients diagnosed with NAFLD. Result: The cost per quality-adjusted life year was above (sic)50 000 for all diagnostic algorithms compared to no-testing. The cost per quality-adjusted life year of the most promising diagnostic algorithm (fibrosis 4-score, enhanced liver fibrosis, vibration controlled transient elastography, and liver biopsy) was similar to(sic)181 000 compared with no testing. Sensitivity analysis indicated that if treatment slowed down disease progression, the value of testing increased. Conclusion: The result questions the overall value of comprehensive diagnostic testing in a broad NAFLD population in current routine clinical care. The role of noninvasive tests may change if evidence-based treatments to slow down disease progression emerge.
|
|
| 42. |
- Hindorf, Cecilia, et al.
(författare)
-
Traceable calibration with 177Lu and comparison of activity meters at hospitals in Norway and Sweden
- 2023
-
Ingår i: Physica medica (Testo stampato). - : Elsevier. - 1120-1797 .- 1724-191X. ; 116
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The activity meter is used to determine the activity of delivered radiopharmaceuticals, administered activity to patients and reference activity when gamma-cameras are calibrated prior to imaged-based dosimetry. The aim is to describe a procedure for cross-calibration of activity meters at different clinical sites, and report on 177Lu activity results when using factory-set calibration factors compared to when calibration is performed with traceability to a primary standard.Methods: Thirty activity meters placed at seven hospitals in Norway and Sweden from four manufacturers: Capintec, Commecer, NuviaTech and Veenstra were included. A stock solution with 177Lu was prepared at the local sites and measured in each activity meter with factory settings. The solution was shipped to the reference site at Lund University for measurements in a secondary standard activity meter. Deviations between local and reference activity measurements were determined for three geometries: 25-mL vial, 10-mL syringe and 1-mL syringe.Results: The median of the deviations was 6.4 % for the 25 mL vial, 5.9 % for the 10 mL syringe and 6.8 % for the 1 mL syringe. The median of the deviations for the 25 mL vial, was 1.5 % for activity meters from Capintec, 7.0 % for Comecer, 11.0 % for NuviaTech and 2.4 % for Veenstra. The majority of the deviations were positive and the maximum deviation was 14.5 %.Conclusion: The activity of 177Lu measured in an activity meter with factory-set dial settings may yield deviations up to 14.5%, compared to activities measured with traceability to a primary standard. This would imply an undertreatment of patients.
|
|
| 43. |
- Honarvar, Hadis, et al.
(författare)
-
Feasibility of Affibody Molecule-Based PNA-Mediated Radionuclide Pretargeting of Malignant Tumors
- 2016
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 6:1, s. 93-103
-
Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are small (7 kDa), non-immunoglobulin scaffold proteins with a potential as targeting agents for radionuclide imaging of cancer. However, high renal re-absorption of Affibody molecules prevents their use for radionuclide therapy with residualizing radiometals. We hypothesized that the use of Affibody-based peptide nucleic acid (PNA)-mediated pretargeting would enable higher accumulation of radiometals in tumors than in kidneys. To test this hypothesis, we designed an Affibody-PNA chimera Z(HER2:342)-SR-HP1 containing a 15-mer HP1 PNA recognition tag and a complementary HP2 hybridization probe permitting labeling with both I-125 and In-111. In-111-Z(HER2:342)-SR-HP1 bound specifically to HER2-expressing BT474 and SKOV-3 cancer cells in vitro, with a K-D of 6+/-2 pM for binding to SKOV-3 cells. Specific high affinity binding of the radiolabeled complementary PNA probe In-111-/I-125-HP2 to Z(HER2:342)-SR-HP1 pre-treated cells was demonstrated. In-111-Z(HER2:342)-SR-HP1 demonstrated specific accumulation in SKOV-3 xenografts in BALB/C nu/nu mice and rapid clearance from blood. Pre-saturation of SKOV-3 with non-labeled anti-HER2 Affibody or the use of HER2-negative Ramos xenografts resulted in significantly lower tumor uptake of In-111-Z(HER2:342)-SR-HP1. The complementary PNA probe In-111/I-125-HP2 accumulated in SKOV-3 xenografts when Z(HER2:342)-SR-HP1 was injected 4 h earlier. The tumor accumulation of In-111/I-125-HP2 was negligible without Z(HER2:342)-SR-HP1 pre-injection. The uptake of In-111-HP2 in SKOV-3 xenografts was 19+/-2 % ID/g at 1 h after injection. The uptake in blood and kidneys was approximately 50- and 2-fold lower, respectively. In conclusion, we have shown that the use of Affibody-based PNA-mediated pretargeting enables specific delivery of radiometals to tumors and provides higher radiometal concentration in tumors than in kidneys.
|
|
| 44. |
- Ilan, Ezgi, et al.
(författare)
-
Comparison of 68Ga-DOTATATE and 177Lu-DOTATATE kinetics in neuroendocrine tumors
-
Tidskriftsartikel (refereegranskat)abstract
- Absorbed dose planning prior peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE would allow maximization of the absorbed dose to tumor tissue whilst minimizing the risk for side-effects in healthy organs. Unfortunately, dosimetry during 177Lu-DOTATATE is only possible post therapy and using 68Ga-DOTATATE to act as surrogate for 177Lu-DOTATATE could potentially enable prediction of absorbed doses prior PRRT with 177Lu-DOTATATE. The aim of this study was to compare uptake and kinetics of 68Ga-DOTATATE and 177Lu-DOTATATE in tumors by performing dynamic or serial scans with both radiopharmaceuticals in the same patients. Methods Six NET patients underwent a 45-min dynamic PET scan after injection of 124 ±38 MBq 68Ga-DOTATATE and serial SPECT scans after a bolus injection of 500 ± 0 MBq 177Lu-DOTATATE assuring similar peptide content in the radiopharmaceuticals. Tumor and whole-blood SUV, tumor-to-blood-ratio (TBR), and net influx rate (Ki) were determined for 68Ga-DOTATATE and 177Lu-DOTATATE. Ki was determined by non-linear regression of an irreversible two-tissue compartment model with a loss parameter and by the Patlak method. Results In majority of tumors, tumor SUV was higher in 68Ga-DOTATATE than in 177Lu-DOTATATE and whole-blood SUV was lower in 68Ga-DOTATATE than in 177Lu-DOTATATE, resulting in a lower TBR for 68Ga-DOTATATE than for 177Lu-DOTATATE. For Ki, Spearman correlation was 0.55 between 68Ga- DOTATATE and 177Lu-DOTATATE with a Demining regression slope of 0.93. For Patlak based Ki (with correction for partial volume effect based on data <100 min p.i. for 177Lu-DOTATATE), the Spearman correlation was 0.90 and with a Deming regression slope close to 1 (0.83). Using a later time interval (with correction for partial volume effect based on data >100 min p.i) for the Patlak analysis also resulted in high correlation (0.87) but the Deming regression slope was 0.18. Conclusion Linear relation with good agreement was found between the SUVs of 68Ga-DOTATATE and 177Lu-DOTATATE. Similar Ki was observed for 68Ga-DOTATATE and 177Lu-DOTATATE during early time interval (<100 min p.i of 177Lu-DOTATATE) however not during late time interval (>100 min p.i.). Hence, late kinetics of 177Lu-DOTATATE cannot be predicted using 68Ga-DOTATATE PET.
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Ilan, Ezgi, et al.
(författare)
-
Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE
- 2015
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:2, s. 177-182
-
Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE.METHODS: Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density sphere model from OLINDA was used for absorbed dose calculations. The absorbed doses were corrected for partial-volume effect based on phantom measurements. On the basis of these results, only tumors larger than 2.2 cm in diameter at any time during the treatment were included for analysis. To further decrease the effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors.RESULTS: Tumor-absorbed doses until best response ranged approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the data, and a significant correlation between the absorbed dose and tumor reduction was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The largest tumor reduction was 57% after a total absorbed dose of 170 Gy.CONCLUSION: The results imply a significant correlation between absorbed dose and tumor reduction. However, further studies are necessary to address the large variations in response for similar absorbed doses.
|
|
| 48. |
|
|
| 49. |
- Ilan, Ezgi, et al.
(författare)
-
Parametric Net Influx Rate Images of 68Ga-DOTATOC and 68Ga-DOTATATE : Quantitative Accuracy and Improved Image Contrast
- 2017
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 58:5, s. 744-749
-
Tidskriftsartikel (refereegranskat)abstract
- (68)Ga-DOTATOC and (68)Ga-DOTATATE are radiolabelled somatostatin analogs used for diagnosis of somatostatin receptor expressing neuroendocrine tumors (NETs) and SUV -measurements are suggested for treatment monitoring. However, changes in net-influx rate (Ki) may better reflect treatment effects than those of the SUV, and accordingly there is a need to compute parametric images showing Ki at the voxel level. The aim of this study was to evaluate parametric methods for computation of parametric Ki images by comparison to volume of interest based methods and to assess image contrast in terms of tumor-to-liver ratio.METHODS: Ten patients with metastatic NETs underwent a 45-min dynamic PET examination followed by whole-body PET/CT at 1 h post injection of (68)Ga-DOTATOC and (68)Ga-DOTATATE on consecutive days. Parametric Ki images were computed using a basis function method (BFM) implementation of the two tissue irreversible compartment model and the Patlak method using a descending aorta image-derived input function, and mean tumor Ki values were determined for 50% isocontour VOIs and compared to Ki values based on non-linear regression (NLR) of the whole-VOI time-activity curve. A subsample of healthy liver was delineated in the whole-body and Ki images and tumor-to-liver ratios were calculated in order to evaluate image contrast. Correlation and agreement between VOI-based and parametric Ki values were assessed using regression and Bland-Altman analysis.RESULTS: Correlation (R2) between NLR-based and parametric image-based (BFM) tumor Ki values was 0.98 (slope 0.81) and 0.97 (slope 0.88) for (68)Ga-DOTATOC and (68)Ga DOTATATE, respectively. For Patlak analysis, correlation between NLR-based and parametric based (Patlak) tumor Ki were 0.95 (slope 0.71) and 0.92 (slope 0.74) for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively. There was no bias between NLR and parametric based Ki-values. Tumor-to-liver contrast was 1.6 and 2.0 times higher in the parametric BFM-Ki images, and 2.3 and 3.0 times in the Patlak images, than in the whole-body images for (68)Ga-DOTATOC and (68)Ga-DOTATATE, respectively.CONCLUSION: A high correlation and agreement between NLR- and parametric based Ki values was found, showing that parametric net influx rate images are quantitatively accurate. In addition, tumor-to-liver contrast was superior in the parametric Ki images compared to whole-body images both for (68)Ga-DOTATOC and (68)Ga DOTATATE.
|
|
| 50. |
- Ilan, Ezgi, et al.
(författare)
-
Tumor-to-blood ratio for assessment of somatostatin receptor density in neuroendocrine tumors using 68Ga-DOTATOC and 68Ga-DOTATATE.
- 2020
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 61:2, s. 217-221
-
Tidskriftsartikel (refereegranskat)abstract
- PET/CT with 68Ga-DOTA-somatostatin analogs has been tested for therapy monitoring in patients with neuroendocrine tumors (NETs). However, standardized uptake values (SUV) in tumors do not correlate with the net influx rate (Ki), as a representation of the somatostatin receptor (SSTR) expression. In this study, tumor-to-blood-ratio (TBR) was evaluated as an alternative tool for semi-quantitative assessment of 68Ga-DOTATOC and 68Ga-DOTATATE tumor uptake and as a therapy monitoring tool for patients with NETs. Methods: Twenty-two NET patients underwent a 45-min dynamic PET/CT scan after injection of 68Ga-DOTATOC and/or 68Ga-DOTATATE. Ki was determined using the Patlak method and TBR was calculated for the 40-45 min time interval. Results: A linear relation was found between Ki and TBR, with a square of Pearson correlation (R2) of 0.98 and 0.93 for 68Ga-DOTATOC and 68Ga-DOTATATE, respectively. Conclusion: High correlation was found between Ki and TBR. Hence, TBR reflects SSTR density more accurately than SUV and is suggested as the preferred metrics for semi-quantitative assessment of 68Ga-DOTATOC and 68Ga-DOTATATE tumor uptake.
|
|
