Alexander Kroiss

Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine: a clarification

Purpose n68Ga-DOTA-Tyr3-octreotide positron emission tomography (68Ga-DOTA-TOC PET) has proven to be superior to 111In-DTPA-D-Phe1-octreotide (111In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of 123I-metaiodobenzylguanidine (123I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard.

68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT.

PurposeWe wanted to establish the range of 68Ga-DOTA-TOC uptake in liver and bone metastases of patients with neuroendocrine tumours (NET) and to establish the range of its uptake in pancreatic NET. This would allow differentiation between physiological uptake and tumour-related somatostatin receptor expression in the pancreas (including the uncinate process), liver and bone. Finally, we wanted to test for differences in patients with NET, either treated or not treated with peptide receptor radionuclide therapy (PRRT).MethodsIn 249 patients, 390 68Ga-DOTA-TOC PET/CT studies were performed. The clinical indications for PET/CT were gastroenteropancreatic NET (194 studies), nongastroenteropancreatic NET (origin in the lung and rectum; 46 studies), NET of unknown primary (111 studies), phaeochromocytoma/glomus tumours (18 studies), and radioiodine-negative metastatic thyroid carcinoma (21 studies).ResultsSUVmax (mean ± standard deviation) values of 68Ga-DOTA-TOC were 29.8u2009±u200916.5 in 162 liver metastases, 19.8u2009±u200918.8 in 89 bone metastases and 34.6u2009±u200917.1 in 43 pancreatic NET (33.6u2009±u200914.3 in 30 tumours of the uncinate process and 36.3u2009±u200921.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (pu2009<u20090.02) was found in liver metastases of NET patients treated with PRRT. There were significant differences in SUVmax between nonmalignant and malignant tissue for both bone and liver metastases and for pancreatic NET including the uncinate process (pu2009<u20090.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUVmax for differentiating tumours in the uncinate process were 93.6xa0% and 90.0xa0%, respectively (pu2009<u20090.0001).Conclusion68Ga-DOTA-TOC is an excellent tracer for the imaging of tumours expressing somatostatin receptors on the tumour cell surface, facilitating the detection of even small tumour lesions. The noninvasive PET/CT approach by measurement of regional SUVmax can offer important clinical information to distinguish between physiological and pathological somatostatin receptor expression, especially in the uncinate process. PRRT does not significantly influence SUVmax, except in liver metastases of patients with NET.

A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma

Purpose18F-Fluoro-l-dihydroxyphenylalanine (18F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by 68Ga-DOTA-Tyr3-octreotide (68Ga-DOTA-TOC) PET. Therefore, we compared 68Ga-DOTA-TOC and 18F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard.MethodsA total of 5 men and 15 women (age range 22 to 73xa0years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68Ga-DOTA-TOC PET and 18F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured.ResultsCompared with anatomical imaging, 68Ga-DOTA-TOC PET and 18F-DOPA PET each had a per-patient and per-lesion detection rate of 100xa0% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of 68Ga-DOTA-TOC was 100xa0% and that of 18F-DOPA PET was 56.0xa0%. Overall, 68Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and 18F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of 68Ga-DOTA-TOC PET was 100xa0% (McNemar, Pu2009<u20090.5), and that of 18F-DOPA PET was 71.1xa0% (McNemar, Pu2009<u20090.001). The SUVmax (mean ± SD) of all 32 concordant lesions was 67.9u2009±u200961.5 for 68Ga-DOTA-TOC PET and 11.8u2009±u20097.9 for 18F-DOPA PET (Mann-Whitney U test, Pu2009<u20090.0001).Conclusion68Ga-DOTA-TOC PET may be superior to 18F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically inoperable tumours and metastatic or multifocal disease.

Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide

PurposeThe aim of this study was to evaluate the impact of 68Ga-labelled DOTA0-lanreotide (68Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or 68Ga-labelled DOTA0,Tyr3-octreotide (68Ga-DOTA-TOC) positron emission tomography (PET).MethodsFifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or 68Ga-DOTA-TOC PET (nu2009=u200938) due to lack of tracer uptake, underwent 68Ga-DOTA-LAN PET to evaluate a treatment option with 90Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150u2009±u200930xa0MBq of each radiopharmaceutical intravenously. PET scans were acquired 60–90xa0min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions.Results68Ga-DOTA-LAN and 68Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of 68Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (nu2009=u200953; pu2009<u20090.0001) and for 68Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (nu2009=u200938; pu2009<u20090.013), respectively. 68Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUVmax) regarding the primary tumour in 25 patients (pu2009<u20090.003) and regarding the liver in 30 patients (pu2009<u20090.009) compared to 68Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. 68Ga-DOTA-TOC revealed more tumour sites than 68Ga-DOTA-LAN (106 vs 53). The tumour to background ratios for tumour and liver calculated from SUVmax measurements were significantly higher for 68Ga-DOTA-TOC than 68Ga-DOTA-LAN (pu2009<u20090.02).Conclusion68Ga-DOTA-TOC PET imaging is an established imaging procedure for accurate staging of NET patients. 68Ga-DOTA-LAN should only be considered as a PET tracer of second choice in patients with no pathologic tracer uptake on 68Ga-DOTA-TOC PET. In these patients, 68Ga-DOTA-LAN PET can provide valuable information when evaluating PRRT as the treatment option, as a broader spectrum of human SSTR subtypes can be detected.

The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma

BackgroundThyroid physiology is closely related to oxidative changes. The aim of this controlled study was to evaluate the levels of nutritional anti-oxidants such as vitamin C, zinc (Zn) and selenium (Se), and to investigate any association of them with parameters of thyroid function and pathology including benign and malignant thyroid diseases.MethodsThis controlled evaluation of Se included a total of 1401 subjects (1186 adults and 215 children) distributed as follows: control group (n = 687), benign thyroid disease (85 children and 465 adults); malignant thyroid disease (2 children and 79 adults). Clinical evaluation of patients with benign thyroid disease included sonography, scintigraphy, as well as the determination of fT3, fT4, TSH, thyroid antibodies levels, Se, Zn, and vitamin C. Besides the routine oncological parameters (TG, TSH, fT4, ultrasound) Se was also determined in the cases of malignant disease. The local control groups for the evaluation of Se levels were taken from a general practice (WOMED) as well as from healthy active athletes. Blood samples were collected between 8:00 and 10:30 a.m. All patients lived in Innsbruck. Statistical analysis was done using SPSS 14.0. The Ho stated that there should be no differences in the levels of antioxidants between controls and thyroid disease patients.ResultsAmong the thyroid disease patients neither vitamin C, nor Zn nor Se correlated with any of the following parameters: age, sex, BMI, body weight, thyroid scintigraphy, ultrasound pattern, thyroid function, or thyroid antibodies. The proportion of patients with benign thyroid diseases having analyte concentrations below external reference cut off levels were 8.7% of cases for vitamin C; 7.8% for Zn, and 20.3% for Se. Low Se levels in the control group were found in 12%. Se levels were significantly decreased in cases of sub-acute and silent thyroiditis (66.4 ± 23.1 μg/l and 59.3 ± 20.1 μg/l, respectively) as well as in follicular and papillary thyroid carcinoma. The mean Se level in the control group was 90.5 ± 20.8 μg/l.ConclusionThe H0 can be accepted for vitamin C and zinc levels whereas it has to be rejected for Se. Patients with benign or malignant thyroid diseases can present low Se levels as compared to controls. Low levels of vitamin C were found in all subgroups of patients.

68 Ga-DOTATOC PET/CT provides accurate tumour extent in patients with extraadrenal paraganglioma compared to 123 I-MIBG SPECT/CT

PurposeThe aim of this study was to compare the accuracy of 123I-MIBG SPECT/CT with that of 68Ga-DOTATOC PET/CT for staging extraadrenal paragangliomas (PGL) using both functional and anatomical images (i.e. combined cross-sectional imaging) as the reference standards.MethodsThe study included three men and seven women (age range 26 to 73xa0years) with anatomical and/or histologically proven disease. Three patients had either metastatic head and neck PGL (HNPGL) or multifocal extraadrenal PGL, and seven patients had nonmetastatic extraadrenal disease. Comparative evaluation included morphological imaging with CT, functional imaging with 68Ga-DOTATOC PET, and 123I-MIBG imaging. The imaging results were analysed on a per-patient and on a per-lesion basis.ResultsOn a per-patient basis, the detection rate of 68Ga-DOTATOC PET was 100xa0%, whereas that of planar 123I-MIBG imaging was 10.0xa0% and with SPECT/CT 20.0xa0% for both nonmetastatic and metastatic/multifocal extraadrenal PGL. On a per-lesion basis, the overall sensitivity of 68Ga-DOTATOC PET was 100xa0% (McNemar pu2009<u20090.5), that of planar 123I-MIBG imaging was 3.4xa0% (McNemar pu2009<u20090.001) and that of SPECT/CT was 6.9xa0% (McNemar pu2009<u20090.001). Both 68Ga-DOTATOC PET and anatomical imaging identified 27 lesions. Planar 123I-MIBG imaging identified only one lesion, and SPECT/CT two lesions. Two additional lesions were detected by 68Ga-DOTATOC PET but not by either 123I-MIBG or CT imaging.ConclusionOur analysis in this patient cohort indicated that 68Ga-DOTATOC PET/CT is superior to 123I-MIBG SPECT/CT, particularly in head and neck and bone lesions, and provides valuable information for staging extraadrenal PGL, particularly in patients with surgically inoperable tumours or multifocal/malignant disease.

Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours

Physiologically increased pancreatic uptake at the head/uncinate process is observed in more than one-third of patients after injection of one of the three 68Ga-labelled octreotide-based peptides used for somatostatin (sst) receptor (r) imaging. There are minor differences between these 68Ga-sstr-binding peptides in the imaging setting. On 68Ga-sstr-imaging the physiological uptake can be diffuse or focal and usually remains stable over time. Differences in the maximal standardised uptake values (SUVmax) reported for the normal pancreas as well as for pancreatic neuroendocrine tumour (PNET) lesions may be related to several factors, including (a) differences in the peptide binding affinities as well as differences in sstr subtype expression of pancreatic α- and β-cells, and heterogeneity / density of tumour cells, (b) differences in scanner resolution, image reconstruction techniques and acquisition protocols, (c) mostly retrospective study designs, (d) mixed patient populations, or (e) interference with medications such as treatment with long-acting sst analogues. The major limitation in most of the studies lies in the lack of histopathological confirmation of abnormal findings. There is a significant overlap between the calculated SUVmax-values for physiological pancreas and PNET-lesions of the head/uncinate process that do not favour the use of quantitative parameters in the clinical setting. Anecdotal long-term follow-up studies have even indicated that increased uptake in the head/uncinate process still can turn out to be malignant over years of follow up. SUVmax-data for the pancreatic body and tail are limited. Therefore, any visible focal tracer uptake in the pancreas must be considered as suspicious for malignancy irrespective of quantitative parameters. In general, sstr-PET/CT has significant implications for the management of NET patients leading to a change in treatment decision in about one-third of patients. Therefore, follow-up with 68Ga-sstr-PET/CT is mandatory in the clinical setting if uptake in the head/uncinate process is observed.

Thyroid carcinoma detected by incidental (18)F-FDG uptake in a patient with progressive cerebellar syndrome.

Thyroid incidentalomas are defined as unexpected, asymptomatic thyroid lesions that are discovered on an imaging study or during surgery unrelated to the thyroid gland. Most of thyroid incidentalomas are benign, though carrying a significant risk of malignancy in about 2 % [1]. F-Fluorodeoxyglucose (FDG) PET/CT was performed in a 57-year-old female patient, suffering from progressive cerebellar syndrome (Fig. 1). The clinical indication was to exclude a paraneoplastic syndrome [2]. To date, only one case report of thyroid carcinoma causing progressive cerebellar degeneration is documented [3]. Besides a reduced uptake of the cerebellum (black arrow a), F-FDG PET/CT detected an incidental focal uptake in the right lobe of the thyroid gland (red arrow a and b). CT showed unclear anatomical correlation (c). A further nuclear medicine investigation of the thyroid gland was recommended. Sonography verified nodules of the right lobe (blue crosses d) and the isthmus region (blue crosses e). Technetium (Tc) scintigraphy showed an unifocal autonomy of the isthmus region (black arrow f), whereas the nodule of the right lobe, positive on F-FDG PET/CT, showed normal uptake in the Tc scintigraphy. A surgery of the thyroid was recommended, in particular due to the strong focal F-FDG uptake of the right thyroid lobe. After performing total thyroidectomy, histology verified a bilateral papillary thyroid carcinoma (pT1a (m) Nx Mx V0 L0 R0, tumor diameter right: one centimeter, left: one millimeter), which led consecutively to perform radioiodine therapy (3.650 megabecquerel). Conclusion Functional imaging (F-FDG PET or F-FDG PET/CT) is crucial in order to detect or exclude a paraneoplastic process in patients with cognitive syndrome. We conclude that incidental focal uptake of the thyroid gland, observed in F-FDG PET/CT, should follow further investigations in order to exclude malignancy [1, 2]. Removal of the tumor in paraneoplastic syndromes of the central nervous system in general is quite unsatisfactory with respect to improvement of neurologic symptoms due to the fact that degeneration in most of the cases is irreversible [3]. This should be considered in the therapeutic management especially in patients in reduced conditions.