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Background. The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer 18F-fluoroazomycin-arabinoside (18FAZA ). Material and methods. Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm3 (+/− 67, SD). Dynamic and static 18FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/− concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk. Results. Five patients had visually identifiable tumours on 18FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five 18FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten 18FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/−12, SD). Conclusion. PET imaging with 18FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of 18FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance. [ABSTRACT FROM AUTHOR]

Purpose: Functional imaging of the adrenal cortex by means of PET may play an important clinical role. Recently, we presented the synthesis and first evaluation of a novel 11β-hydroxylase inhibitor, [18F] FETO, in rats displaying high tracer accumulation in the adrenals. In this study, we aimed to investigate for the first time the potency of [18F]FETO as a PET tracer for the adrenal cortex in humans. Methods: An average preparation yielded 1-2 GBq of [18F]FETO ready to use. Ten healthy volunteers aged 24-57 years (five male and five female) were included in the study. After i.v. administration of 365 MBq [18F] FETO (246-391 MBq), dynamic images were acquired in 2D standard mode in 14 frames over 45 min. Afterwards, whole-body scanning was performed. In addition to visual interpretation, semi-quantitative analysis using standardised uptake values (SUVs) was conducted. Results: [18F]FETO distribution was similar in all scanned volunteers. Visually, pronounced accumulation of [18F] FETO was found in the adrenals, whereas moderate uptake was observed—at least in some of the subjects—for liver, renal calices, gallbladder, stomach walls and pancreas. Kidney and bowels showed only faint uptake. Median SUVs for the right and left adrenal glands were 15.6 (10.0-28.6) and 15.7 (10.3-35.9), respectively. The reference tissue (liver) displayed a median SUV of 2.5 (2.2-4.6). Conclusion: [18F]FETO is a valuable tracer for adrenocortical PET imaging, combining the longer half-life of 18F with a high 11β-hydroxylase selectivity. In accordance with our findings in rats, FETO PET revealed very high accumulation in the adrenal glands in healthy volunteers. [ABSTRACT FROM AUTHOR]

Aim: To describe the (18)F-fluorodihydro-xyphenylalanine ((18)F-DOPA), positron emission tomography (PET) and magnetic resonance imaging (MRI) appearance of pheochromocytomas, with a focus on the presence or absence of typical MRI features., Materials and Methods: Eleven patients with histologically-verified pheochromocytoma [sporadic (n=9), multiple endocrine neoplasia (MEN) 2A syndrome (n=2)] were enrolled retrospectively. All patients underwent an MRI examination of the upper abdomen. Nine out of 11 patients underwent (18)F-DOPA PET/CT, and the remaining two patients underwent independent PET and computed tomography (CT) examinations. (18)F-DOPA-PET/CT examinations were considered positive when an increased tracer accumulation in the adrenal region, as shown on CT images, was observed. When an adrenal mass was detected on MRI, the T1 and T2 signal intensity and contrast enhancement pattern were recorded. Based on MR characteristics, the lesions were divided into typical and atypical., Results: Ten out of 11 patients had one lesion, while one patient had two lesions. All pheochromocytomas were detected by both PET/CT and MRI. On (18)F-DOPA scans, all lesions showed an increased tracer accumulation, with a mean maximum standardized uptake value (SUVmax) of 13.7±5.75. Eight out of 12 pheochromocytomas exhibited typical MRI features, with intermediate signal intensity on T1-weighted images in-phase, absence of signal drop on T1-weighted images out-of-phase, high signal intensity on T2-weighted images, and clear contrast enhancement in the arterial phase. The remaining four lesions exhibited atypical MRI features, namely absence of one of the listed criteria., Conclusion: In the assessment of pheochromocytoma, the combination of (18)F-DOPA PET with MRI is superior to MRI-alone. (18)F-DOPA PET/MRI may yield a higher diagnostic confidence for the detection of pheochromocytoma than (18)F-DOPA PET/CT.

Background: The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer (18)F-fluoroazomycin-arabinoside ((18)FAZA )., Material and Methods: Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm(3) (+/- 67, SD). Dynamic and static (18)FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/- concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk., Results: Five patients had visually identifiable tumours on (18)FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five (18)FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten (18)FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/-12, SD)., Conclusion: PET imaging with (18)FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of (18)FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance.

The aim of the study was to evaluate the possible changes in CD4+ and CD8+ T-cell cytokine production patterns in Hashimoto's thyroiditis (HT) with elevated calcitonin (CT). Fourteen consecutive patients with verified HT were included in the present study. Patients were divided into two groups. Group I: 7 HT patients with elevated CT levels (>10 pg/ml); Group II: 7 HT patients with CT levels <10 pg/ml). All patients underwent intracellular cytokine detection in CD4+ and CD8+ T-cells of peripheral blood mononuclear cells (PBMC) by flow cytometry. Patients with elevated CT levels (group I) had significantly higher percentages of CD8+ cells producing IFN-gamma compared to healthy donors. A detailed analysis of cytokine production patterns revealed that this was accompanied by an increased frequency of single IFN-gamma positive cells, i.e., cells not expressing most of the other cytokines tested. Similarly, patients in group I also showed higher percentages of CD8+ TNF-alpha positive cells than healthy donors. In this case, cells co-expressing TNF-alpha and IFN-gamma were found at significantly higher frequencies. No increase in Th1 type cytokines, such as IFN-gamma or TNF-alpha, was detectable in CD4+ T-cells. In contrast, CD4+ T-cells from group I patients showed significantly higher percentages of cells producing Th2 cytokines, such as IL-4 or IL-13. The lack of increased Th1 cytokine production accompanied by an increased Th2 cytokine production seems to be a special feature of HT patients with elevated CT levels that may reflect a pathogenetic mechanism for tumor initiation.

The measurement of basal serum calcitonin (CT) in patients with evidence of Hashimoto's thyroiditis (HT) has been proposed in a recent study demonstrating an increased prevalence of elevated basal and stimulated CT. The aim of this study was to evaluate the frequency and relevance of elevated CT levels in HT. The basal sera CT were measured in 568 consecutive HT patients using a chemiluminescent immuno-assay. Whenever the serum CT was > 10 pg/ml, a pentagastrin (PG) stimulation test was performed. Two patients with abnormal/pathological PG tests were identified. Total thyroidectomy and lymph node dissection revealed for the first patient medullary thyroid carcinoma (MTC) and for the second patient C cell hyperplasia (CCH), together with papillary thyroid carcinoma. Our data showed a low prevalence of MTC and its premalignant condition CCH in HT patients; nevertheless, the patient with MTC presented lymph node metastasis. The fact that both cases presented without evidence of nodular thyroid disease highlights the persistent diagnostic dilemma of CT screening programs.