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Purpose: 18 F-Fluoro-L-dihydroxyphenylalanine ( 18 F-DOPA) PET offers high sensitivity and specificity in the imaging of non-malignant head and neck paraganglioma (HNPGL) but lower sensitivity in metastatic disease of these neuroendocrine tumours (NET). In contrast to the radiotracer 18 F-DOPA, both 123 I-meta-iodo-benzylguanidine ( 123 I-MIBG) and 68 Ga-DOTA-Tyr3-octreotide ( 68 Ga-DOTA-TOC) offer valuable clinical information on norepinephrine and somatostatin (SST) receptor status for planning 131 I-MIBG and radionuclide peptide therapy (PRRT), respectively. Therefore, we compared 68 Ga-DOTA-TOC and 18 F-DOPA PET/CT with 123 I-MIBG planar and SPECT/CT imaging, for the detection of HNPGL. Combined cross-sectional imaging was the reference standard., Methods: A total of 3 men and 7 women (age range 22 to 73 years) with anatomical and/or histologically proven HNPGL were included in this study. Of these patients, 3 patients had metastatic HNPGL. Comparative evaluation included morphological imaging with CT and functional imaging with 68 Ga-DOTA-TOC and 18 F-DOPA PET, including 123 I-MIBG imaging. The imaging results were analysed on a per-patient and per-lesion basis., Results: On a per-patient analysis, the detection rate of both 68 Ga-DOTA-TOC PET/CT and 18 F-DOPA PET/CT was 100%, that of planar 123 I-MIBG imaging 10.0% and that of SPECT/CT 20.0%. On a per-lesion basis and in reference to diagnostic CT, the sensitivity of 68 Ga-DOTA-TOC PET/CT was 100% (McNemar, P < 0.5), that of 18 F-DOPA PET/CT was 66.7% (McNemar, P < 0.01), that of planar 123 I-MIBG imaging was 3.7% (McNemar, P < 0.0001), and that of SPECT/CT was 7.4% (McNemar, P < 0.0001) in HNPGL. Overall, 68 Ga-DOTA-TOC PET identified 29 lesions and anatomical imaging identified 27 lesions. 18 F-DOPA PET identified 18 lesions, whereas planar 123 I-MIBG imaging identified 1 lesion and SPECT/CT 2 lesions., Conclusion: 68 Ga-DOTA-TOC PET/CT is superior for imaging, non-malignant and metastatic HNPGL compared to 18 F-DOPA PET/CT and planar 123 I-MIBG imaging, including SPECT/CT, particularly in bone lesions. Combined functional/anatomical imaging ( 68 Ga-DOTA-TOC PET/CT) enables excellent delineation of tumour extent in these rare tumour entities. Compared to 123 I-MIBG scintigraphy, 68 Ga-DOTA-TOC PET appears far more useful for planning radionuclide therapy in patients with surgically inoperable tumours or metastatic disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Pheochromocytoma (PHEO) is rare and belongs to the group of neuroendocrine tumours (NETs). These tumours can be found anywhere from the neck to the pelvis associated with sympathetic ganglia. Morphological imaging, for example CT, provides excellent anatomical detail and high sensitivity but lacks specificity as difficulties may occur when distinguishing between tumours derived from the sympathetic nervous system and other tumour entities. In contrast to anatomical imaging, functional imaging ( 123 I-MIBG, 68 Ga-DOTA-TOC PET) provides high sensitivity and specificity in detecting NETs. Early detection of PHEO is crucial and has a major effect on treatment and prognosis. This case report describes the important role of anatomical and functional imaging in a patient with a neuroendocrine tumour of unusual origin., (Copyright © 2018. Publicado por Elsevier España, S.L.U.)

Purpose: To determine the value of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT)., Methods: We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined (68)Ga-DOTA-TOC and (18)F-FDG PET/CT studies. (68)Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 - 9 months. (18)F-FDG PET/CT was done within 2 months of (68)Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months)., Results: All patients were (68)Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 (18)F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were (18)F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were (18)F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were (18)F-FDG-negative initially but (18)F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were (18)F-FDG-positive initially but (18)F-FDG-negative during follow-up (group 4).(18)F-FDG PET showed more and/or larger metastases than (68)Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 - 82 % from the first to the last follow-up investigation., Conclusion: In NET patients, the presence of (18)F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with (18)F-FDG-negative NET may show (18)F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have (18)F-FDG-positive tumours. Therefore, (18)F-FDG PET/CT is a complementary tool to (68)Ga-DOTA-TOC PET/CT with clinical relevance for molecular investigation.

Purpose: PET/CT with (68)Ga-labelled [DOTA(0),Tyr(3)]-octreotide ((68)Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased (68)Ga-DOTA-TOC uptake indicating expression of SSTR., Methods: Five patients with untreated, histologically proven EBV-positive NPC were referred for (68)Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios., Results: Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases., Conclusion: (68)Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC.

Purpose: The aim of this study was to compare the accuracy of (123)I-MIBG SPECT/CT with that of (68)Ga-DOTATOC PET/CT for staging extraadrenal paragangliomas (PGL) using both functional and anatomical images (i.e. combined cross-sectional imaging) as the reference standards., Methods: The study included three men and seven women (age range 26 to 73 years) 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 (68)Ga-DOTATOC PET, and (123)I-MIBG imaging. The imaging results were analysed on a per-patient and on a per-lesion basis., Results: On a per-patient basis, the detection rate of (68)Ga-DOTATOC PET was 100 %, whereas that of planar (123)I-MIBG imaging was 10.0 % and with SPECT/CT 20.0 % for both nonmetastatic and metastatic/multifocal extraadrenal PGL. On a per-lesion basis, the overall sensitivity of (68)Ga-DOTATOC PET was 100 % (McNemar p < 0.5), that of planar (123)I-MIBG imaging was 3.4 % (McNemar p < 0.001) and that of SPECT/CT was 6.9 % (McNemar p < 0.001). Both (68)Ga-DOTATOC PET and anatomical imaging identified 27 lesions. Planar (123)I-MIBG imaging identified only one lesion, and SPECT/CT two lesions. Two additional lesions were detected by (68)Ga-DOTATOC PET but not by either (123)I-MIBG or CT imaging., Conclusion: Our analysis in this patient cohort indicated that (68)Ga-DOTATOC PET/CT is superior to (123)I-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.

Purpose: (18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-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 (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard., Methods: A total of 5 men and 15 women (age range 22 to 73 years) 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 (68)Ga-DOTA-TOC PET and (18)F-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., Results: Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P < 0.5), and that of (18)F-DOPA PET was 71.1% (McNemar, P < 0.001). The SUVmax (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for (68)Ga-DOTA-TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P < 0.0001)., Conclusion: (68)Ga-DOTA-TOC PET may be superior to (18)F-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.

Purpose: We wanted to establish the range of (68)Ga-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)., Methods: In 249 patients, 390 (68)Ga-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)., Results: SUVmax (mean ± standard deviation) values of (68)Ga-DOTA-TOC were 29.8 ± 16.5 in 162 liver metastases, 19.8 ± 18.8 in 89 bone metastases and 34.6 ± 17.1 in 43 pancreatic NET (33.6 ± 14.3 in 30 tumours of the uncinate process and 36.3 ± 21.5 in 13 tumours of the pancreatic tail). A significant difference in SUVmax (p < 0.02) 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 (p < 0.0001). At a cut-off value of 17.1 the specificity and sensitivity of SUVmax for differentiating tumours in the uncinate process were 93.6 % and 90.0 %, respectively (p < 0.0001)., Conclusion: (68)Ga-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.

Purpose: The aim of this study was to evaluate the impact of (68)Ga-labelled DOTA(0)-lanreotide ((68)Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or (68)Ga-labelled DOTA(0),Tyr(3)-octreotide ((68)Ga-DOTA-TOC) positron emission tomography (PET)., Methods: Fifty-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 (68)Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent (68)Ga-DOTA-LAN PET to evaluate a treatment option with (90)Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 ± 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min 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., Results: (68)Ga-DOTA-LAN and (68)Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of (68)Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for (68)Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. (68)Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV(max)) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to (68)Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. (68)Ga-DOTA-TOC revealed more tumour sites than (68)Ga-DOTA-LAN (106 vs 53). The tumour to background ratios for tumour and liver calculated from SUV(max) measurements were significantly higher for (68)Ga-DOTA-TOC than (68)Ga-DOTA-LAN (p < 0.02)., Conclusion: (68)Ga-DOTA-TOC PET imaging is an established imaging procedure for accurate staging of NET patients. (68)Ga-DOTA-LAN should only be considered as a PET tracer of second choice in patients with no pathologic tracer uptake on (68)Ga-DOTA-TOC PET. In these patients, (68)Ga-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.

Purpose: (68)Ga-DOTA-Tyr(3)-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) has proven to be superior to (111)In-DTPA-D-Phe(1)-octreotide ((111)In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard., Methods: Three male and eight female patients (age range 3 to 68 years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with (68)Ga-DOTA-TOC PET and (123)I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis., Results: On a per-patient basis, both (68)Ga-DOTA-TOC and (123)I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 91.7% and that of (123)I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 97.2% and that of (123)I-MIBG was 90.7%. Overall, in this patient cohort, (68)Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and (123)I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of (68)Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p<0.0001) and that of (123)I-MIBG was 76.9% (McNemar p<0.0001)., Conclusion: Our analysis in this relatively small patient cohort indicates that (68)Ga-DOTA-TOC PET may be superior to (123)I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and neuroblastoma.

Unlabelled: (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) PET has proven its usefulness in the diagnosis of patients with neuroendocrine tumors. Radionuclide therapy ((90)Y-DOTA-TOC or (177)Lu-DOTA-octreotate) is a choice of treatment that also requires an accurate diagnostic modality for early evaluation of treatment response. Our study compared (68)Ga-DOTA-TOC PET with CT or MRI using the Response Evaluation Criteria in Solid Tumors. Furthermore, standardized uptake values (SUVs) were calculated and compared with treatment outcome., Methods: Forty-six patients (29 men, 17 women; age range, 34-84 y) with advanced neuroendocrine tumors were investigated before and after 2-7 cycles of radionuclide therapy. Long-acting somatostatin analogs were not applied for at least 6 wk preceding the follow-up. Data were acquired with a dedicated PET scanner. Emission image sets were acquired at 90-100 min after injection. (68)Ga-DOTA-TOC PET images were visually interpreted by 2 experienced nuclear medicine physicians. For comparison, multislice helical CT scans and 1.5-T MRI scans were obtained. Attenuation-corrected PET images were used to determine SUVs. Repeated CT evaluation and other imaging modalities, for example, (18)F-FDG, were used as the reference standard., Results: According to the reference standard, (68)Ga-DOTA-TOC PET and CT showed a concordant result in 32 patients (70%). In the remaining 14 patients (30%), discrepancies were observed, with a final outcome of progressive disease in 9 patients and remission in 5 patients. (68)Ga-DOTA-TOC PET was correct in 10 patients (21.7%), including 5 patients with progressive disease. In these patients, metastatic spread was detected with the follow-up whole-body PET but was missed when concomitant CT was used. On the other hand, CT confirmed small pulmonary metastases not detected on (68)Ga-DOTA-TOC in 1 patient and progressive liver disease not detected on (68)Ga-DOTA-TOC in 3 patients. Quantitative SUV analysis of individual tumor lesions showed a large range of variability., Conclusion: (68)Ga-DOTA-TOC PET shows no advantage over conventional anatomic imaging for assessing response to therapy when all CT information obtained during follow-up is compared. Only the development of new metastases during therapy was detected earlier in some cases when whole-body PET was used. SUV analysis of individual lesions is of no additional value in predicting individual responses to therapy.

Unlabelled: Somatostatin receptor scintigraphy is an accurate imaging modality for the diagnosis of neuroendocrine tumor. Because detection of distant metastases has a major impact on treatment, early diagnosis of metastatic spread is of great importance. So far, no standard procedure has become established for the early diagnosis of bone metastases from neuroendocrine tumor. We compared the diagnostic value of CT with that of the novel somatostatin analog (68)Ga-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ((68)Ga-DOTATOC) in the detection of such metastases., Methods: Fifty-one patients (22 women and 29 men; age range, 32-87 y) with histologically verified neuroendocrine tumor were included in this study. PET scans were fused with CT scans using a vacuum fixation device. (18)F-NaF or (99m)Tc-dicarboxypropane diphosphonate bone scans or clinical follow-up served as the reference standard., Results: Twelve of the 51 patients had no evidence of bone metastases on any of the available imaging modalities, and 37 patients had (68)Ga-DOTATOC PET results true-positive for bone metastases. (68)Ga-DOTATOC PET results were true-negative for 12 patients, false-positive for one, and false-negative for another, resulting in a sensitivity of 97% and a specificity of 92%. (68)Ga-DOTATOC PET detected bone metastases at a significantly higher rate than did CT (P < 0.001). Furthermore, conventional bone scans confirmed the results of somatostatin receptor PET but did not reveal additional tumors in any patients., Conclusion: (68)Ga-DOTATOC PET is a reliable, novel method for the early detection of bone metastases in patients with neuroendocrine tumor. Our results show that CT and conventional bone scintigraphy are less accurate than (68)Ga-DOTATOC PET in the primary staging or restaging of neuroendocrine tumor.

Unlabelled: The aim of this study was to evaluate the diagnostic value of a new somatostatin analog, (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1)-Tyr(3)-octreotide ((68)Ga-DOTA-TOC), for PET in patients with known or suspected neuroendocrine tumors. PET was compared with conventional scintigraphy and dedicated CT., Methods: Eighty-four patients (48 men, 36 women; age range, 28-79 y; mean age +/- SD, 58.2 +/- 12.2 y) were prospectively studied. For analysis, patients were divided into 3 groups: detection of unknown primary tumor in the presence of clinical or biochemical suspicion of neuroendocrine malignancy (n = 13 patients), initial tumor staging (n = 36 patients), and follow-up after therapy (n = 35 patients). Each patient received 100-150 MBq (68)Ga-DOTA-TOC. Imaging results of PET were compared with (99m)Tc-labeled hydrazinonicotinyl-Tyr(3)-octreotide ((99m)Tc-HYNIC-TOC) and (111)In-DOTA-TOC. CT was also performed on every patient using a multidetector scanner. Each imaging modality was interpreted separately by observers who were unaware of imaging findings before comparison with PET. The gold standard for defining true-positive (TP), true-negative (TN), false-positive (FP), and false-negative (FN) results was based on all available histologic, imaging, and follow-up findings., Results: PET was TP in 69 patients, TN in 12 patients, FP in 1 patient, and FN in 2 patients, indicating a sensitivity of 97%, a specificity of 92%, and an accuracy of 96%. The FP finding was caused by enhanced tracer accumulation in the pancreatic head, and the FN results were obtained in patients with a tumor of the gastrointestinal tract displaying liver metastases. (68)Ga-DOTA-TOC showed higher diagnostic efficacy compared with SPECT (TP in 37 patients, TN in 12 patients, FP in 1 patient, and FN in 34 patients) and diagnostic CT (TP in 41 patients, TN in 12 patients, FP in 5 patients, and FN in 26 patients). This difference was of statistical significance (P < 0.001). However, the combined use of PET and CT showed the highest overall accuracy., Conclusion: (68)Ga-DOTA-TOC PET shows a significantly higher detection rate compared with conventional somatostatin receptor scintigraphy and diagnostic CT with clinical impact in a considerable number of patients.