Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with 111 In-diethylenetriaminepentaacetic acidoctreotide, scintigraphy with 123 I-metaiodobenzylguanidine (MIBG), and 18 F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, 123 I-MIBG scintigraphy, and 18 F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. Results: The overall sensitivity of SRS, 123 I-MIBG scintigraphy, and 18 F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were 18 F-FDG PET-positive, of which 3 were also 123 I-MIBG scintigraphypositive, giving a combined overall sensitivity of 96%. SRS also exceeded 123 I-MIBG scintigraphy and 18 F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. 123 I-MIBG scintigraphy was superior to 18 F-FDG PET for ileal neuroendocrine tumors, and 18 F-FDG PET was superior to 123 I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of 18 F-FDG PET (92%) exceeded that of both SRS (69%) and 123 I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of 123 I-MIBG scintigraphy and 18 F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, 18 F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, 18 F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.

The use of positron emitter-labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first-in-humans use of 64 Cu-DOTATATE, an avidly binding somatostatin receptor ligand linked to a radioisotope with intermediate half-life and favorable positron energy (half-life, 12.7 h; maximum positron energy, 0.653 MeV). Methods: In a prospective setup, 14 patients with a history of neuroendocrine tumors underwent both PET/CT with 64 Cu-DOTATATE and SPECT/CT with our current routine imaging agent 111 In-diethylenetriaminepentaacetic acid-octreotide. After intravenous injection of 193-232 MBq of 64 Cu-DOTATATE, whole-body PET scans were acquired at 1 h (n 5 14), 3 h (n 5 12), and 24 h (n 5 5) after administration. Tissue radioactivity concentrations for normal organs and lesions were quantified, and standardized uptake values were calculated for the early (1 h) and delayed (3 h) scans. Using the data for 5 patients, we assessed the radiation dose with OLINDA/EXM software. Furthermore, the clinical performance of 64 Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64 Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3 h. Compared with conventional scintigraphy, 64 Cu-DOTATATE PET identified additional lesions in 6 of 14 patients (43%). In 5 patients, lesions were localized in organs and organ systems not previously known as metastatic sites, including the early-stage detection of a secondary neuroendocrine tumor in a patient with a known mutation in the multiple endocrine neoplasia type I gene. All major additional findings seen only on PET could be confirmed on the basis of a clinical follow-up interval of 18 mo. Calculated radiation dose estimates yielded an effective dose of 6.3 mSv for an injected activity of 200 MBq of 64 Cu-DOTATATE, with the liver being the organ with the highest absorbed radiation dose (0.16 mGy/MBq).Conclusion: This first-in-humans study supports the clinical use of 64 Cu-DOTATATE for SRI with excellent imaging quality, reduced radiation burden, and increased lesion detection rate when compared with 111 In-diethylenetriaminepentaacetic acid-octreotide.

Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of 64 Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head basis the performance of 64 In-diethylenetriaminepentaacetic acid (DTPA)-octreotide ( 111 In-DTPA-OC) as a basis for implementing 64 Cu-DOTATATE as a routine. Methods: We prospectively enrolled 112 patients with pathologically confirmed NETs of gastroenteropancreatic or pulmonary origin. All patients underwent both PET/CT with 64 Cu-DOTATATE and SPECT/CT with 111 In-DTPA-OC within 60 d. PET scans were acquired 1 h after injection of 202 MBq (range, 183-232 MBq) of 64 Cu-DOTATATE after a diagnostic contrast-enhanced CT scan. Patients were followed for 42-60 mo for evaluation of discrepant imaging findings. The McNemar test was used to compare the diagnostic performance. Results: Eightyseven patients were congruently PET-and SPECT-positive. No SPECT-positive cases were PET-negative, whereas 10 false-negative SPECT cases were identified using PET. The diagnostic sensitivity and accuracy of 64 Cu-DOTATATE (97% for both) were significantly better than those of 111 In-DTPA-OC (87% and 88%, respectively, P 5 0.017). In 84 patients (75%), 64 Cu-DOTATATE identified more lesions than 111 In-DTPA-OC and always at least as many. In total, twice as many lesions were detected with 64 Cu-DOTATATE than with 111 In-DTPA-OC. Moreover, in 40 of 112 cases (36%) lesions were detected by 64 Cu-DOTATATE in organs not identified as disease-involved by 111 In-DTPA-OC. Conclusion: With these results, we demonstrate that 64 Cu-DOTATATE is far superior to 111 In-DTPA-OC in diagnostic performance in NET patients. Therefore, we do not hesitate to recommend implementation of 64 Cu-DOTATATE as a replacement for 111 In-DTPA-OC.