| 41. |
- Christersson, Albert, et al.
(författare)
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Presurgical localization of infected avascular bone segments in chronic complicated posttraumatic osteomyelitis in the lower extremity using dual-tracer PET/CT.
- 2018
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Localizing and removing the infected sequestrum in long-standing trauma-related chronic osteomyelitis remains a clinical challenge. PET/CT with 18F-fluorodeoxyglucose (FDG-PET) has a high sensitivity for chronic osteomyelitis and 18F-sodium-fluoride PET/CT (NaF-PET) has a high specificity for identifying non-viable bone. Combining both, high signal on FDG-PET in the bone without signal on NaF-PET could potentially guide surgery to become more precise with curative intent. Eight patients with long-standing (average 22 years) posttraumatic (n = 7) or postoperative (n = 1) chronic osteomyelitis in the lower extremity and with multiple futile attempts for curative surgery were recruited in this prospective pilot study. FDG-PET and NaF-PET were performed within a week in between using standard scanning protocols. The most likely location of the culprit sequestrum was identified and was surgically removed. Based on perioperative tissue cultures, antibiotics were given for 6-8 months. Dual-tracer (FDG- and NaF-PET/CT) was performed again after 12 months to rule out persisting signs of infection.RESULTS: A likely culprit sequestrum could preoperatively be identified by dual-tracer PET in all eight cases and in four cases an additional sequestrum was identified at a location with no clinical sign of infection. The infected necrotic tissue was removed during surgery. Follow-up dual-tracer PET revealed no signs of persistent infection. All patients recovered with no clinical signs of recurrence for a follow-up of mean 4.5 (SD 1.3) years.CONCLUSIONS: Dual-tracer PET/CT with FDG and NaF allows successful precise surgery with curative intent in patients with long-standing complicated posttraumatic chronic osteomyelitis with severely deranged anatomy.
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| 42. |
- Dalmo, Johanna, et al.
(författare)
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Evaluation of retinol binding protein 4 and carbamoylated haemoglobin as potential renal toxicity biomarkers in adult mice treated with Lu-177-octreotate
- 2014
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:59
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Tidskriftsartikel (refereegranskat)abstract
- Background: The kidneys are regarded as one of the main dose-limiting organs in the treatment of neuroendocrine tumours with Lu-177-[DOTA(0), Tyr(3)]-octreotate (Lu-177-octreotate), despite the successful use of kidney uptake blocking agents such as lysine and arginine. To avoid renal toxicity but still give each patient as high amount of Lu-177-octreotate as possible, there is a need for methods/biomarkers that indicate renal injury in an early stage of the treatment. The aim of this study was to investigate the potential of using urinary retinol binding protein 4 (RBP4) and carbamoylated haemoglobin (Hb) in blood as biomarkers of nephrotoxic effects on adult mice after Lu-177-octreotate treatment. Methods: Adult BALB/c nude mice were injected with 60 MBq or 120 MBq of Lu-177-octreotate or with saline (control). Urine was collected before injection and concentrations of urinary RBP4 and creatinine were determined 14 to 90 days after injection Blood samples were collected after 90 days, and carbamoylated N-terminal valine in Hb, formed from urea, was measured as valine hydantoin (VH) after detachment from Hb. Results: The RBP4 values increased with administered activity and time. For the 60 and 120 MBq groups, statistically significantly higher RBP4 levels (p <0.05) were found at day 60 and 90 compared to baseline, also at day 30 for 120 MBq group. For VH, the mean values were similar for the 60 MBq and control groups, while a small increase was observed for the 120 MBq group; but there were no statistically significant differences between any of the groups (p >0.05). No morphological changes in the kidney tissue were found. Conclusions: Urinary RBP4 is a promising new biomarker for radiation-induced renal toxicity. For the conditions used in this experiment, carbamoylated Hb (from urea) measured as VH may not be a sufficiently sensitive biomarker to be used for renal toxicity.
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| 43. |
- Dalmo, Johanna, et al.
(författare)
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Priming increases the anti-tumor effect and therapeutic window of 177Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1.
- 2017
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 177Lu-[DOTA0, Tyr3]-octreotate (177Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase 177Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a 177Lu-octreotate priming dose followed 24 h later by a second injection of 177Lu-octreotate compared to a single administration of 177Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice. RESULTS: Priming resulted in a 1.9 times higher mean absorbed dose to the tumor tissue per administered activity, together with a reduced mean absorbed dose for kidneys. Priming gave the best overall anti-tumor effects. Magnetic resonance imaging showed no statistically significant difference in tumor response between treatment with and without priming. Gene expression analysis demonstrated effects on cell cycle regulation. Biological processes associated with apoptotic cell death were highly affected in the biodistribution and dosimetry study, via differential regulation of, e.g., APOE, BAX, CDKN1A, and GADD45A. CONCLUSIONS: Priming had the best overall anti-tumor effects and also resulted in an increased therapeutic window. Results indicate that potential biomarkers for tumor regrowth may be found in the p53 or JNK signaling pathways. Priming administration is an interesting optimization strategy for 177Lu-octreotate therapy of neuroendocrine tumors, and further studies should be performed to determine the mechanisms responsible for the reported effects.
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| 44. |
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| 45. |
- Economou Lundeberg, Johan, et al.
(författare)
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Comparison between silicon photomultiplier-based and conventional PET/CT in patients with suspected lung cancer—a pilot study
- 2019
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lung cancer is one of the most common cancers in the world. Early detection and correct staging are fundamental for treatment and prognosis. Positron emission tomography with computed tomography (PET/CT) is recommended clinically. Silicon (Si) photomultiplier (PM)-based PET technology and new reconstruction algorithms are hoped to increase the detection of small lesions and enable earlier detection of pathologies including metastatic spread. The aim of this study was to compare the diagnostic performance of a SiPM-based PET/CT (including a new block-sequential regularization expectation maximization (BSREM) reconstruction algorithm) with a conventional PM-based PET/CT including a conventional ordered subset expectation maximization (OSEM) reconstruction algorithm. The focus was patients admitted for 18F-fluorodeoxyglucose (FDG) PET/CT for initial diagnosis and staging of suspected lung cancer. Patients were scanned on both a SiPM-based PET/CT (Discovery MI; GE Healthcare, Milwaukee, MI, USA) and a PM-based PET/CT (Discovery 690; GE Healthcare, Milwaukee, MI, USA). Standardized uptake values (SUV) and image interpretation were compared between the two systems. Image interpretations were further compared with histopathology when available. Results: Seventeen patients referred for suspected lung cancer were included in our single injection, dual imaging study. No statically significant differences in SUVmax of suspected malignant primary tumours were found between the two PET/CT systems. SUVmax in suspected malignant intrathoracic lymph nodes was 10% higher on the SiPM-based system (p = 0.026). Good consistency (14/17 cases) between the PET/CT systems were found when comparing simplified TNM staging. The available histology results did not find any obvious differences between the systems. Conclusion: In a clinical setting, the new SiPM-based PET/CT system with a new BSREM reconstruction algorithm provided a higher SUVmax for suspected lymph node metastases compared to the PM-based system. However, no improvement in lung cancer detection was seen.
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| 46. |
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| 47. |
- Elgström, Erika, et al.
(författare)
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Role of CD8-positive cells in radioimmunotherapy utilizing (177)Lu-mAbs in an immunocompetent rat colon carcinoma model.
- 2015
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- CD8-positive cells might play a crucial role in the therapeutic response to radiation, which has however not been investigated in radioimmunotherapy (RIT). The aim of this study was to evaluate whether cytotoxic T cells affect the response of established tumors and, above all, if they delay or prevent the development of distant metastases after RIT, using an immunocompetent syngeneic rat colon carcinoma model.
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| 48. |
- Eriksson, Jonas, et al.
(författare)
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Strategy to develop a MAO-A-resistant 5-hydroxy-L-[beta-C-11]tryptophan isotopologue based on deuterium kinetic isotope effects
- 2014
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe serotonin precursor 5-hydroxy-L-[β-11C]tryptophan ([11C]HTP) is in clinical use for localization of neuroendocrine tumors and has been suggested as a proxy marker for pancreatic islet cells. However, degradation by monoamine oxidase-A (MAO-A) reduces retention and the contrast to non-endocrine tissue.MethodsA synthesis method was developed for 5-hydroxy-L-[β-11C2H]tryptophan ([11C]DHTP), an isotopologue of [11C]HTP, labeled with 11C and 2H at the β-position adjacent to the carbon involved in MAO-A decarboxylation. MAO-A-mediated degradation of [11C]DHTP was evaluated and compared to non-deuterated [11C]HTP.Results[11C]DHTP was synthesized with a radiochemical purity of >98%, radioactivity of 620 ± 190 MBq, and deuterium (2H or 2H2) incorporation at the β-position of 22% ±5%. Retention and resistance to MAO-A-mediated degradation of [11C]DHTP were increased in cells but not in non-human primate pancreas.ConclusionsPartial deuteration of the β-position yields improved resistance to MAO-A-mediated degradation in vitro but not in vivo.
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| 49. |
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| 50. |
- Fridén, Markus, et al.
(författare)
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Identification of positron emission tomography (PET) tracer candidates by prediction of the target-bound fraction in the brain
- 2014
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Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Development of tracers for imaging with positron emission tomography (PET) is often a time-consuming process associated with considerable attrition. In an effort to simplify this process, we herein propose a mechanistically integrated approach for the selection of tracer candidates based on in vitro measurements of ligand affinity (K-d), non-specific binding in brain tissue (V-u,V-brain), and target protein expression (B-max). Methods: A dataset of 35 functional and 12 non-functional central nervous system (CNS) PET tracers was compiled. Data was identified in literature for K-d and B-max, whereas a brain slice methodology was used to determine values for V-u,V-brain. A mathematical prediction model for the target-bound fraction of tracer in the brain (f(tb)) was derived and evaluated with respect to how well it predicts tracer functionality compared to traditional PET tracer candidate selection criteria. Results: The methodology correctly classified 31/35 functioning and 12/12 non-functioning tracers. This predictivity was superior to traditional classification criteria or combinations thereof. Conclusions: The presented CNS PET tracer identification approach is rapid and accurate and is expected to facilitate the development of novel PET tracers for the molecular imaging community.
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