| 1. |
- Jensen, Robert T., et al.
(författare)
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Unmet Needs in Functional and Nonfunctional pancreatic neuroendocrine neoplasms
- 2019
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 26-36
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the European Neuroendocrine Tumor Society (ENETS) held working sessions composed of members of the advisory board and other neuroendocrine neoplasm (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This report briefly summarizes the main proposed areas of unmet needs in patients with functional and nonfunctional pancreatic NENs.
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| 2. |
- Nilsson, Johan, et al.
(författare)
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Paracetamol analogues conjugated by FAAH induce TRPV1-mediated antinociception without causing acute liver toxicity
- 2021
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Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 213
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Tidskriftsartikel (refereegranskat)abstract
- Paracetamol, one of the most widely used pain-relieving drugs, is deacetylated to 4-aminophenol (4-AP) that undergoes fatty acid amide hydrolase (FAAH)-dependent biotransformation into N-arachidonoylphenolamine (AM404), which mediates TRPV1-dependent antinociception in the brain of rodents. However, paracetamol is also converted to the liver-toxic metabolite N-acetyl-p-benzoquinone imine already at therapeutic doses, urging for safer paracetamol analogues. Primary amine analogues with chemical structures similar to paracetamol were evaluated for their propensity to undergo FAAH-dependent N-arachidonoyl conjugation into TRPV1 activators both in vitro and in vivo in rodents. The antinociceptive and antipyretic activity of paracetamol and primary amine analogues was examined with regard to FAAH and TRPV1 as well as if these analogues produced acute liver toxicity. 5-Amino-2-methoxyphenol (2) and 5-aminoindazole (3) displayed efficient target protein interactions with a dose-dependent antinociceptive effect in the mice formalin test, which in the second phase was dependent on FAAH and TRPV1. No hepatotoxicity of the FAAH substrates transformed into TRPV1 activators was observed. While paracetamol attenuates pyrexia via inhibition of brain cyclooxygenase, its antinociceptive FAAH substrate 4-AP was not antipyretic, suggesting separate mechanisms for the antipyretic and antinociceptive effect of paracetamol. Furthermore, compound 3 reduced fever without a brain cyclooxygenase inhibitory action. The data support our view that analgesics and antipyretics without liver toxicity can be derived from paracetamol. Thus, research into the molecular actions of paracetamol could pave the way for the discovery of analgesics and antipyretics with a better benefit-to-risk ratio.
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| 3. |
- Ramage, John K, et al.
(författare)
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Colorectal Neuroendocrine Neoplasms - areas of unmet need
- 2019
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 108:1, s. 45-53
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Tidskriftsartikel (refereegranskat)abstract
- The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.
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| 4. |
- Bergh, Anders, et al.
(författare)
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Cobalt-mediated solid phase synthesis of 3-O-alkynylbenzyl galactosides and their evaluation as galectin inhibitors
- 2006
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020. ; 62:35, s. 8309-8317
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Tidskriftsartikel (refereegranskat)abstract
- Methyl beta-D-galactoside was converted to the corresponding 3,4-O-stannylene acetal, which was selectively benzylated with 3-iodobenzyl bromide and coupled to a polymer-bound propargylic ether via a Sonogashira reaction. The polymer-bound carbohydrate substrate was cleaved from the resin with different carbon nucleophiles in a cobalt-mediated Nicholas reaction. The product 3-O-alkynylbenzyl galactosides were screened towards galectin-1, -3, -7, -8N and -9N in a competitive fluorescence polarisation assay. Particularly potent inhibitors were identified against galectin-7 with affinity enhancements up to one order of magnitude due to the 3-O-alkynylbenzyl moiety. (c) 2006 Elsevier Ltd. All rights reserved.
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| 5. |
- Berglund, Karin, 1967-
(författare)
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Jakten på Entreprenörer : Om öppningar och låsningar i entreprenörskapsdiskursen
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Entrepreneurs are expected to play a crucial role in times of unemployment and economical regression. A “hunt for entrepreneurs” can thus be said to be occurring as they appear to be people who can save nations, societies, and companies in troublesome situations. The project Diversity in Entrepreneurship (DiE) aimed to introduce a broad view of entrepreneurship in a regional context. Three development areas are emphasized that are strategically important to transforming a traditional industrial community into an entrepreneurial region: paying attention to the spirit of enterprise among underrepresented groups; stimulating entrepreneurship among young people; and considering the importance of culture in stimulating a diverse and entrepreneurial society.An equality discourse is introduced through DiE that – emphasising social and mundane occurrences - stands in contrast to the historically rooted enterprise discourse that proffers companies as productive apparatus, where a few competent people – often men – have been, and still are, in charge. In the equality discourse, all people in the region make a difference, not merely a few. The encounter of the two discourses has resulted in confusion, and thus conflicts and collisions; but also in new possibilities.A new perspective of entrepreneurship and regional development is developed where conflicts are put forward as constructive. That the two discourses met on the same regional scene is therefore seen as positive as many people have been made aware of the social, political, and economic contradictions which restrain some groups in society from creating a (working) life. Hence, the contradictions have enabled the inhabitants to see themselves, and others, as entrepreneurs in regional development processes. Openings have thus emerged to view entrepreneurship from a broader perspective that includes people, to create practices through which a more diverse working life is becoming discernible.
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| 13. |
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| 14. |
- Dahlman, Pär
(författare)
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CT Urography : Efforts to Reduce the Radiation Dose
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Computed tomography urography (CTU) is today the imaging method used to investigate patients with suspected urinary tract malignancy, replacing the old imaging method intravenous pyelography (IVP) about a decade ago. The downside of this shift was that the effective radiation dose to the examined patient was eight times higher for CTU compared to IVP. Based on four different studies, the present thesis focused on efforts to reduce the CTU radiation dose. In study I, the number of cysts and solid lesions in the separate scan phases was evaluated in 57 patients undergoing four-phase CTU 1997-98. The number of scans was reduced from four to three when the nephrographic scan was abolished following study I.Study II registered the diameter of renal cell carcinoma (RCC) and the presenting symptoms in the total number of patients (n=232) diagnosed with RCC between 1997 and 2003. The results from study II showed that the critical size for RCCs to cause macroscopic hematuria was ≥ 4 cm. Study III was a dose-escalation study aimed to decide the minimal possible tube load in the unenhanced and excretory phase scans if the low dose images are reviewed together with normal dose corticomedullary phase images. Study III showed that it is possible to reduce the mean effective dose in three phase CTU from 16.2 mSv to 9.4 mSv with a combined low and normal dose CTU protocol. Study IV investigated the changes in the CTU protocol between 1997 and 2008, and the development of the effective radiation dose. Study IV clarified how the CTU protocol has changed between 1997 and 2008 and as a result the mean effective radiation dose to patients undergoing CTU in 2008 is only 39% of the effective dose in 1997. In conclusion, the findings from the studies included in this thesis have contributed to a reduced radiation dose to patients undergoing CTU. The mean effective dose from CTU is at present only three times higher compared to that from the IVP.
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| 15. |
- Delanaye, Pierre, et al.
(författare)
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Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil, and Africa
- 2022
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 38:1, s. 106-118
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A new Chronic Kidney Disease Epidemiology equation without race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared to the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts.METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France, (n = 4429, including 964 Black Europeans), from Brazil (n = 100), and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed.RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73m², and accuracy within 30% of 86.9 and 87.4, respectively versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value ( = concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans, and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males.CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated, population-specific Q-values presents the best performance in the whole age range in the European and African populations included in this study.
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| 16. |
- Delanaye, Pierre, et al.
(författare)
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Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment
- 2022
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Ingår i: British Journal of Clinical Pharmacology. - : Wiley-Blackwell Publishing Inc.. - 0306-5251 .- 1365-2125. ; 88:5, s. 2118-2127
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14,804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR), and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision, and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age, and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages.RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR<60 mL/min and at BMI [18.5-25[kg/m2 , all equations performed similarly and for BMI<18.5kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI≥25kg/m2 the bias of the CG increased with increasing BMI (+17.2mL/min at BMI≥40kg/m2 ). The four more recent equations also classified mGFR stages better than CG.CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for GFR, age, and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.
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| 17. |
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| 18. |
- Hasan, Mahmudul, et al.
(författare)
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The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5-epimerization of glucuronic acid in higher organisms
- 2021
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Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 12:5, s. 1869-1885
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Tidskriftsartikel (refereegranskat)abstract
- Dermatan sulfate epimerase 1 (DS-epi1, EC 5.1.3.19) catalyzes the conversion of d-glucuronic acid to l-iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS-epi1, solved at 2.4 Å resolution, as well as a model of the full-length luminal protein obtained by a combination of macromolecular crystallography and targeted cross-linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS-epi1, involving a His/double-Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal-coordinating center and pattern of N-glycosylation of the protein. Additionally, the structure of DS-epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS-epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitors.
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| 19. |
- Hennings, Joakim, 1969-, et al.
(författare)
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11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism
- 2010
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Ingår i: Langenbeck's archives of surgery (Print). - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 395:7, s. 963-967
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate whether dexamethasone suppression treatment can improve 11 C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA). Materials and Methods: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small “hot-spot” regions of interest (ROIs) comprising 4-pixels (SUVhs) and 1-pixel (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded. Results: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to non-functional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p<0.05) but tumour SUV was not significantly decreased after suppression in either PA or non-functional tumours (p>0.05). However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p>0.05). Conclusion: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series dexamethasone-suppressed MTO-PET was ubable to increase the tumour-to-normal-adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.
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| 20. |
- Hennings, Joakim, et al.
(författare)
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Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism
- 2010
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Ingår i: Langenbeck's archives of surgery (Print). - : Springer Science and Business Media LLC. - 1435-2443 .- 1435-2451. ; 395:2, s. 133-137
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.
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| 21. |
- Loskog, Angelica, et al.
(författare)
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Immunostimulatory AdCD40L gene therapy combined with low-dose cyclophosphamide in metastatic melanoma patients
- 2016
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 114:8, s. 872-880
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Current approaches for treating metastatic malignant melanoma (MM) are not effective enough and are associated with serious adverse events. Due to its immunogenicity, melanoma is an attractive target for immunostimulating therapy. In this phase I/IIa study, local AdCD40L immunostimulatory gene therapy was evaluated in patients with MM.METHODS: AdCD40L is an adenovirus carrying the gene for CD40 ligand. Patients that failed standard treatments were enrolled. Six patients received four weekly intratumoral AdCD40L injections. Next, nine patients received low-dose cyclophosphamide conditioning before the first and fourth AdCD40L injection. The blood samples were collected at multiple time points for chemistry, haematology and immunology evaluations. Radiology was performed at enrolment and repeated twice after the treatment.RESULTS: AdCD40L was safe with mild transient reactions. No objective responses were recorded by MRI, however, local and distant responses were seen on FDG-PET. The overall survival at 6 months was significantly better when cyclophosphamide was added to AdCD40L. The patients with the best survival developed the highest levels of activated T cells and experienced a pronounced decrease of intratumoral IL8.CONCLUSIONS: AdCD40L therapy for MM was well tolerated. Local and distant responses along with better survival in the low-dose cyclophosphamide group are encouraging.
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| 22. |
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| 23. |
- Norlén, Olov, et al.
(författare)
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11C-5-hydroxytryptophan positron emission tomography after radiofrequency ablation of neuroendocrine tumor liver metastases
- 2012
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:6, s. 883-890
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim was to assess the feasibility of C-11-5-hydroxy-tryptophan positron emission tomography ( C-11-5-HTP-PET) in the follow-up after radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumors (NETS). Background: Contrast-enhanced computed tomography (CECT) and contrast-enhanced ultrasound (CEUS) are commonly used to evaluate the liver after RFA of NETs. In general, C-11-5-HTP-PET is more sensitive in the visualization of NETs, but no studies have investigated its role after RFA.Methods: Six consecutive patients with liver metastases from NETs were subjected to RFA treatment. All patients underwent baseline imaging before RFA and on two occasions (1-2 and 6-11 months) after RFA. The imaging consisted of C-11-5-HTP-PET, CEUS and CECT on all three occasions.Results: Thirty RFA areas were evaluated, and residual tumors (RTs) were depicted in eight areas (22%). C-11-5-HTP-PET depicted RTs after RFA with maximum sensitivity (100%) and specificity (100%), using radiological follow-up as the gold standard. C-11-5-HTP-PET detected five out of eight RTs earlier than CECT or CEUS. In general, the sensitivity of C-11-5-HTP-PET exceeded that of CECT and CEUS for early visualization of NET liver metastases.Conclusion: C-11-5-HTP-PET can be used in the follow-up after RFA for the purpose of detecting RT, and it provides additional information to CEUS and CECT by detecting new lesions.
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| 24. |
- Pottel, Hans, et al.
(författare)
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Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
- 2023
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.METHODSWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.RESULTSOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.CONCLUSIONSThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations.
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| 25. |
- Pottel, Hans, et al.
(författare)
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Cystatin C–Based Equation to Estimate GFR without the Inclusion of Race and Sex
- 2023
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 388:4, s. 333-343
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C–based EKFC equation would increase the accuracy of estimated GFR is unknown.MethodsWe used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex.ResultsOn the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83+0.005×(age–50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone.ConclusionsThe EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.)
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| 26. |
- Pottel, Hans, et al.
(författare)
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Development and Validation of a Modified Full Age Spectrum Creatinine-Based Equation to Estimate Glomerular Filtration Rate : A Cross-sectional Analysis of Pooled Data
- 2021
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 174:2, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low.OBJECTIVE: To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations.DESIGN: Cross-sectional analysis with separate pooled data sets for development and validation.SETTING: = 13) with measured GFR available.PATIENTS: 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set).MEASUREMENTS: Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR.RESULTS: ] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations.LIMITATION: No Black patients were included.CONCLUSION: The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels.PRIMARY FUNDING SOURCE: Swedish Research Council (Vetenskapsrådet).
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| 27. |
- Pottel, Hans, et al.
(författare)
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Standardization of serum creatinine is essential for accurate use of unbiased estimated GFR equations : evidence from three cohorts matched on renal function
- 2022
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Ingår i: Clinical Kidney Journal. - : Oxford University Press. - 2048-8505 .- 2048-8513. ; 15:12, s. 2258-2265
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR).Methods: White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age +/- 3 years, BMI +/- 2.5 kg/m(2)) and renal function (mGFR +/- 3 ml/min/1.73 m(2)). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria.Results: For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 +/- 0.20 versus 0.86 +/- 0.23, males 1.06 +/- 0.23 versus 1.12 +/- 0.37; P > .05) but significantly different from the CRIC [females 1.13 +/- 0.23 (P < .0001), males 1.42 +/- 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts.Conclusion: Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.Lay Summary: Standardization of serum creatinine (SCr) measurement is fundamental for estimating glomerular filtration rate (GFR). We used data with GFR measured by a reference method from three cohorts: Chronic Renal Insufficiency Cohort (CRIC, n = 1548), Minnesota cohort (n = 1093) and European Kidney Function Consortium cohort (EKFC; n = 7727). In the EKFC and Minnesota cohorts, SCr was measured by standardized methods, although SCr 'calibration' was more debatable in the CRIC. GFR was measured by the same method in the CRIC and Minnesota cohort. Then we matched 305 White subjects for sex, measured GFR (+/- 3 ml/min/1.73 m(2)), age (+/- 3 years) and body mass index (+/- 2.5 kg/m(2)). From these matched subjects we showed that the association between SCr and measured GFR was quite similar between subjects from the Minnesota and EKFC cohorts, but different between the CRIC and EKFC cohort and between the Minnesota cohort and CRIC. These differences lead to discrepancies in the analysis of the performance of different creatinine-based equations.
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| 28. |
- Radecka, Eva, et al.
(författare)
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An unusual case of tumor thrombus in the inferior vena cava : A case report
- 2003
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 44:2, s. 160-161
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Tidskriftsartikel (refereegranskat)abstract
- Adrenal cortical carcinoma (ACC) is a rare malignancy. Patients present either with a functional tumor or secondary to mass effect. In non-functioning tumors, the tumor size often exceeds 5 cm by the time of diagnosis, and tumor thrombus can occur. We report on a case of a small non-functioning ACC causing a large tumor thrombus in the inferior vena cava.
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| 29. |
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| 30. |
- Silins, Isabella, 1983-, et al.
(författare)
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First-in-human evaluation of [18F]CETO : a novel tracer for adrenocortical tumours
- 2023
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Nature. - 1619-7070 .- 1619-7089. ; 50:2, s. 398-409
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Tidskriftsartikel (refereegranskat)abstract
- Purpose[11C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [11C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[18F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[18F]fluoroethyletomidate positron emission computed tomography ([18F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers.MethodsFifteen patients underwent [18F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [15O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [18F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis.ResultsUptake of [18F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [18F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K1. Both K1 and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K1, SUV65–70, and SUV120 were 25, 22, and 17%.ConclusionsHigh adrenal uptake combined with a low unspecific liver uptake suggests that 18F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate Ki.Trial registrationClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083
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| 31. |
- Silins, Isabella, 1983-, et al.
(författare)
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Radiation dosimetry of para-chloro-2-[18F]fluoroethyl-etomidate:a PET tracer for adrenocortical imaging
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction[11C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer’s rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[18F]fluoroethyl-etomidate, [18F]CETO, a fluorine-18 (T1/2=109.8 min) analogue, as a potential new adrenocortical PET tracer.ObjectivesThe aim of this study was to assess in vivo and in-human radiation dosimetry of [18F]CETO.Methods: Residence times were calculated based on uptake data from rats (n=30, biodistribution study with ex vivo measurements) as well as in vivo PET/CT in cynomolgus (n=1) and humans (n=9). OLINDA 1.1 was used to obtain absorbed doses in human organs (mGy/MBq) and effective dose (mSv/MBq).Results[18F]CETO showed a high uptake in human adrenal glands, still increasing at 90 minutes post injection. Regardless of species used for input data (rat, cynomolgus or human), adrenal glands (absorbed dose 0.093 ± 0.038 mGy/MBq based on human data) were confirmed as the dose-limiting organs. The effective dose based on human data was 18.2 μSv/MBq and varied little when using rat (18.4 μSv/MBq) or cynomolgus data (16.1 μSv/MBq). Conclusions[18F]CETO has a favourable biodistribution in humans for adrenal imaging. The effective dose for a typical clinical PET/CT examination with 200 MBq [18F]CETO is 3.6 mSv.
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| 32. |
- Sundín, Anders, et al.
(författare)
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Computed tomography of experimental liver metastases using an iodinated hepatocyte-specific lipid emulsion : a correlative study in the nude rat
- 1994
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Ingår i: Investigative Radiology. - 0020-9996 .- 1536-0210. ; 29:11, s. 963-969
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE AND OBJECTIVES: A hepatocyte-specific iodinated lipid emulsion, NRI 757, was used for detection of experimental hepatic metastases. MATERIALS AND METHODS: The study was performed in a correlative model of multiple hepatic metastases from a human colonic cancer implanted in the nude rat. RESULTS: After intravenous injection, normal liver parenchyma remained enhanced for several hours, whereas the uptake in hepatic metastases was negligible. A liver-to-lesion contrast of 45 Hounsfield units (HU) was obtained at a dose of 1 mL NRI 757/kg body weight (BW). In a lesion-by-lesion analysis of 177 metastases ranging in size from 1 to 32 mm, the mean +/- standard deviation overall detection rate for native scanning and contrast-enhanced scanning in vivo and post mortem, 20 +/- 0.4%, 53 +/- 5.2%, and 55 +/- 4.0%, respectively and 28%, 84%, and 82%, retrospectively. When metastatic size also was considered, for native scanning the maximum detection rate of 61% was reached for 8- to 10-mm lesions, whereas for contrast-enhanced computed tomography scanning, 100% of the 5- to 7-mm lesions and 42% of the 1- to 2-mm nodules were detected. CONCLUSION: The use of NRI 757 improved the diagnostic yield considerably.
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| 33. |
- Sundín, Anders, et al.
(författare)
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Contrast-enhanced CT scanning in vivo for the quantification of hepatic metastases from a human colonic cancer in the nude rat
- 1992
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 18:6, s. 615-623
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic metastases were induced in nude rats by intraportal injection of 2.5-5.0 x 10(6) cells from the human colonic cancer cell line LS 174 T. Quantification of tumour burden, expressed as relative metastatic area, was performed by contrast-enhanced computed tomography (CT) scanning in vivo (n = 14), contrast enhanced CT scanning post mortem (n = 21) and computer-based area calculation (CBAC) (n = 21). To determine the false-positive contribution to the estimated tumour burden by the evaluation procedures themselves, six rats without metastases were assessed. The quantification in the three different assessment groups was in close accordance in animals with an intermediate or extensive metastatic burden, but not in rats with a minor (< 4%) tumour burden. The results indicate that contrast-enhanced CT scanning can be used in this model to quantify hepatic metastases, except in animals with few and small lesions. Furthermore, the results suggest a potential for the assessment of therapeutic response by repeated contrast-enhanced CT scanning in vivo, as well as prospects for a corresponding evaluation in man.
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| 34. |
- Sundin, Johanna, et al.
(författare)
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High yield direct 76Br-bromination of monoclonal antibodies using Cloramine-T
- 1999
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Ingår i: Nuclear Medicine and Biology. - 0969-8051 .- 1872-9614. ; 26:8, s. 923-929
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibody (MAb) A33 was labeled with the positron emitter 76Br (T(1/2) = 16.2 h). Direct labeling was done using the conventional chloramine-T method. After optimization of the labeling conditions, a maximum yield (mean +/- max error) of 77 +/- 2% was obtained at pH 6.8. In vitro binding of 76Br-A33 to SW1222 colonic cancer cells showed that the immunoreactivity was retained. Also, the MAbs 38S1 and 3S193 and the peptide hEGF were 76Br-labeled, resulting in labeling yields (mean +/- max error) of 75 +/- 3%, 63 +/- 4%, and 73 +/- 0.1%, respectively. We conclude that antibodies and peptides can be labeled conveniently with 76Br for the purpose of whole-body tumour imaging by positron emission tomography.
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| 35. |
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| 36. |
- Wang, Chen, et al.
(författare)
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Dysprosium-enhanced MR imaging for tumor tissue characterization : an experimental study in a human xenograft model
- 1997
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Ingår i: Acta Radiologica. - 0284-1851 .- 1600-0455. ; 38:2, s. 281-286
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate dysprosium-enhanced MR imaging for differentiation between morphologically intact and necrotic tumor tissue in a tumor model. MATERIAL AND METHODS: A human colon carcinoma was transplanted subcutaneously into 9 nude (immunodeprived) rats. MR imaging was performed before and after injection of the dysprosium agent Dy-DTPA-BMA. T1-, T2- and T2*-weighted sequences were acquired. The tumors were dissected, histological sections were prepared, and compared with corresponding MR images. RESULTS: In intact tissue, the MR signal intensity in the T2- and T2*-weighted images decreased after Dy injection and the delineation of the intact regions were sharp and corresponded well to the gross histological sections. CONCLUSION: Dy-enhanced MR imaging facilitated the differentiation between intact and necrotic tumor tissue.
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| 37. |
- Zhao, Qinghai, et al.
(författare)
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Effects of dextranation on the pharmacokinetics of short peptides : A PETstudy on mEGF
- 1999
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Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 10:6, s. 938-946
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Tidskriftsartikel (refereegranskat)abstract
- The effects of dextranation on the biodistribution of mouse epidermal growth factor (mEGF, 6 kDa) were assessed. By reductive amination, mEGF was coupled to 13 and 46 kDa dextran. The two dextranated conjugates and free mEGF were labeled with the positron-emitting nuclide (76)Br (T(1/2) = 16 h). After intravenous administration to Sprague Dawley rats, the radioactivity biodistribution was evaluated by positron emission tomography (PET) and by measurements of dissected tissues. The dextranation prolonged the retention time in blood, especially when the dextran chain was long. [(76)Br]mEGF-dextran conjugates were shown to have significantly, more than 5 times, lower kidney accumulation than the nonconjugated [(76)Br]mEGF. In conclusion, dextranation affects the biodistribution of mEGF in vivo giving a prolonged circulation time, a decreased uptake in kidney, and an increased spleen accumulation.
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| 38. |
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| 39. |
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| 40. |
- Almqvist, Ylva, et al.
(författare)
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Biodistribution of At-211-Labeled humanized monoclonal antibody A33
- 2007
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 22:4, s. 480-487
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Tidskriftsartikel (refereegranskat)abstract
- Radioimmunotherapy (RIT) could be a possible adjuvant treatment method for patients with colorectal carcinoma. The A33 antigen is a promising RIT target, as it is highly and homogenously expressed in 95% of all colorectal carcinomas. In this study, the humanized monoclonal antibody A33 (huA33), targeting the A33 antigen, was labeled with the therapeutic nuclide 211At, and the biodistribution and in vivo targeting ability of the conjugate was investigated in an athymic mouse xenograft model. There was an accumulation of 211At in tumor tissue over time, but no substantial accumulation was seen in any organ apart from the skin and thyroid, indicating no major release of free 211At in vivo. At all time points, the uptake of 211At-huA33 was higher in tumor tissue than in most organs, and at 8 hours postinjection (p.i.), no organ had a higher uptake than tumor tissue. The tumor-to-blood ratio of 211At-huA33 increased with time, reaching 2.5 after 21 hours p.i. The highest absorbed dose was found in the blood, but the tumor received a higher dose than any organ other than the thyroid. An in vivo blocking experiment showed that 211At-huA33 binds specifically to human tumor xenografts in athymic mice. In conclusion, the favorable biodistribution and specific in vivo targeting ability of 211At-huA33 makes it a potential therapeutic agent for the RIT of metastatic colorectal carcinoma.
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| 41. |
- Almqvist, Ylva, et al.
(författare)
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In vitro and in vivo characterization of 177Lu‑huA33 : A radioimmunoconjugate against colorectal cancer
- 2006
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 33:8, s. 991-998
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of (177)Lu-labeled huA33. METHODS: huA33 was labeled with the beta-emitting therapeutic nuclide (177)Lu using the chelator CHX-A"-DTPA, and the properties of the (177)Lu-CHX-A"-huA33 ((177)Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells. RESULTS: The (177)Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a K(D) value of 2.3+/-0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of (177)Lu-huA33 was very high, peaking at 134+/-21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70+/-30, 10 days pi. Throughout the study, the uptake of (177)Lu in bone (known to accumulate free (177)Lu) was low, and the fraction of protein-bound (177)Lu in plasma samples was high (95% to 99%). This indicates high stability of the (177)Lu-huA33 conjugate in vivo. CONCLUSION: The (177)Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.
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| 42. |
- Almqvist, Ylva, et al.
(författare)
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In vitro characterization of 211 At-labeled antibody A33 : a potential therapeutic agent against metastatic colorectal carcinoma
- 2005
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 20:5, s. 514-523
-
Tidskriftsartikel (refereegranskat)abstract
- The humanized antibody A33 binds to the A33 antigen, expressed in 95% of primary and metastatic colorectal carcinomas. The restricted pattern of expression in normal tissue makes this antigen a possible target for radioimmunotherapy of colorectal micrometastases. In this study, the A33 antibody was labeled with the therapeutic nuclide 211At using N-succinimidyl para-(tri-methylstannyl)benzoate (SPMB). The in vitro characteristics of the 211At-benzoate-A33 conjugate (211At-A33) were investigated and found to be similar to those of 125I-benzoate-A33 (125I-A33) in different assays. Both conjugates bound with high affinity to SW1222 cells (Kd = 1.7 ± 0.2 nM, and 1.8 ± 0.1 nM for 211At-A33 and 125I-A33, respectively), and both showed good intracellular retention (70% of the radioactivity was still cell associated after 20 hours). The cytotoxic effect of 211At-A33 was also confirmed. After incubation with 211At-A33, SW1222 cells had a survival of approximately 0.3% when exposed to some 150 decays per cell (DPC). The cytotoxic effect was found to be dose-dependent, as cells exposed to only 56 DPC had a survival of approximately 5%. The 211At-A33 conjugate shows promise as a potential radioimmunotherapy agent for treatment of micrometastases originating from colorectal carcinoma.
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| 43. |
- Almqvist, Ylva, 1974-
(författare)
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Targeted Therapy of Colorectal Cancer : Preclinical Evaluation of a Radiolabelled Antibody
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Targeted radiotherapy (TRT) of cancer is a promising approach that enables selective treatment of tumour cells, while sparing normal tissue. The humanized monoclonal antibody A33 (huA33) is a potential targeting agent for TRT of colorectal cancer, since its antigen is expressed in more than 95 % of all colorectal carcinomas. The aim of this thesis was to evaluate the therapeutic potential of the two huA33-based TRT-conjugates, 177Lu-huA33, and 211At-huA33. The conjugates 177Lu-huA33, and 211At-huA33, bound specifically to colorectal cancer cells, both in vitro and in vivo. A dose dependent cytotoxic effect of 211At-huA33 was also demonstrated in vitro. From a therapeutic perspective, both conjugates had a favourable biodistribution in tumour-bearing nude mice, with high tumour uptake and a low uptake in normal organs (with the exception of an expected thyroid uptake of 211At). After injection of 211At-huA33, the blood absorbed a slightly higher dose than the tumour, but for 177Lu-huA33, the tumour received a 12 times higher dose than blood. Two days after intravenous injection of 177Lu-huA33 in tumour-bearing mice, the tumours could be clearly visualised by gamma camera imaging, with very low interference from normal tissue radioactivity. In an experimental therapy study, also performed in tumour-bearing mice, there was an excellent therapeutic effect of 177Lu-huA33. About 50 % of the treated animals were tumour free 140 days after injection of 177Lu-huA33, while none of the non-radioactive controls survived beyond 20 days after injection of treatment substances. In conclusion, this thesis demonstrates that the therapeutic conjugates 177Lu-huA33, and 211At-huA33, are promising targeting agents that might help improve therapy of colorectal cancer.
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| 44. |
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| 45. |
- Ambrosini, Valentina, et al.
(författare)
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Consensus on molecular imaging and theranostics in neuroendocrine neoplasms
- 2021
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 146, s. 56-73
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Forskningsöversikt (refereegranskat)abstract
- Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.
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| 46. |
- Ambrosini, Valentina, et al.
(författare)
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Use and perceived utility of [18 F]FDG PET/CT in neuroendocrine neoplasms : A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022.
- 2024
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Ingår i: Journal of neuroendocrinology. - 0953-8194 .- 1365-2826. ; 36:1, s. e13359-
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Tidskriftsartikel (refereegranskat)abstract
- Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.
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| 47. |
- Andersson, Camilla, et al.
(författare)
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Assessment of Whether Patients' Knowledge, Satisfaction, and Experience Regarding Their 18F-Fluoride PET/CT Examination Affects Image Quality
- 2016
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Ingår i: Journal of Nuclear Medicine Technology. - : Society of Nuclear Medicine. - 0091-4916 .- 1535-5675. ; 44:1, s. 21-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate patients’ previous knowledge, satisfaction and experience regarding a (18F)-fluoride positron emission tomography / computed tomography examination ((18F)-fluoride PET/CT) and to explore whether experienced discomfort during the examination or pain was associated with reduced image quality. A further aim was to explore whether patients’ health-related quality of life (HRQoL) was associated with their satisfaction and experiences of the examination.Methods: Fifty consecutive patients with a histopathological diagnosis of prostate cancer who were scheduled for (18F)-fluoride PET/CT were asked to participate in the study, which was performed between November 2011 and April 2013. A questionnaire was used to collect information regarding the patients’ previous knowledge and experience of the examination. Image quality assessment was performed according to an arbitrary scale. The EORTC-QLQ-C30 and QLQ-PR25 were used to assess HRQoL.Results: Forty-six patients (96%) completed the questionnaires. Twenty-six per cent of participants did not know at all what a (18F)-fluoride PET/CT examination was. The majority (52-70%) were to a very high degree satisfied with the care provided by the nursing staff but less satisfied with the information given prior to the examination. The image quality was similar in patients who were exhausted or claustrophobic during the examination and those who were not. No correlations between HRQoL and the participants’ experience of (18F)-fluoride PET/CT were found.Conclusion: The majority of participants were satisfied with the care provided by the nursing staff, but there is still room for improvement especially regarding the information prior to the examination. Long examination time may be strenuous, for the patient but there was no difference in image quality between patients who felt discomfort during the examination or pain and those who did not.
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| 48. |
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| 49. |
- Andersson, Jesper L, et al.
(författare)
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A method for coregistration of PET and MR brain images
- 1995
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 36:7, s. 1307-1315
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Tidskriftsartikel (refereegranskat)abstract
- Combining MRI morphological data with functional PET data offers significant advantages in research as well as in many clinical situations. Automatic methods are needed, however, to coregister the data from the two modalities.METHODS:Simulated PET images were created by simple and automatic segmentation of MR images followed by the assignment of different uptake values to various tissue types. The simulated PET images were registered to actual PET images using a pixel-by-pixel, PET-PET registration method. The transformation matrix was then applied to the MR images. The method was used to register MRI data to PET transmission scans and emission scans obtained with FDG, nomifensine and raclopride. Validation was performed by comparing the results to those obtained by matching internal points manually defined in both volumes.RESULTS:Emission and transmission PET images were successfully registered to MR data. Comparison to the manual method indicated a registration accuracy on the order of 1-2 mm in each direction. No difference in accuracy between the different tracers was found. The error sensitivity for the method's assumptions seemed to be sufficiently low to allow complete automation of the method.CONCLUSION:We present a rapid, robust and fully automated method to register PET and MR brain images with sufficient accuracy for most clinical applications.
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| 50. |
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