Comparison of the Impact of 68Ga-DOTATATE and 18F-FDG PET/CT on Clinical Management in Patients with Neuroendocrine Tumors.

This study aimed to assess the clinical impact of 68Ga-DOTATATE and 18F-FDG with respect to the management plan and to evaluate the prognostic value of both tracers. A total of 104 patients (55 male and 49 female; median age, 58 y; range, 20-90 y) with histologically proven neuroendocrine tumors (NETs) underwent both 68Ga-DOTATATE and 18F-FDG PET/CT. Twenty-eight patients (26.9%) had poorly differentiated tumors, and 76 (73.1%) had well-differentiated tumors. PET/CT results and SUVs were compared with prognostic factors such as histologic grade (G1, G2, or G3, for low-grade [well differentiated], intermediate-grade [moderately differentiated], and high-grade [poorly differentiated], respectively), chromogranin A, and proliferation index (Ki-67). The 68Ga-DOTATATE and 18F-FDG PET/CT findings were discordant in 65 patients (62.5%) and concordant in 39 patients (37.5%). The results changed the therapeutic plan in 84 patients (80.8%). In 22 patients (21.1%), decision making was based on the 18F-FDG findings; in 32 (30.8%), on the findings with both radiotracers; and in 50 (48.1%), on the 68Ga-DOTATATE findings. The most frequent management decision based on 18F-FDG was initiation of chemotherapy (10 patients, 47.6%). The most common treatment decision due to 68Ga-DOTATATE was initiation of peptide receptor radionuclide therapy (14 patients, 27.4%). In 11 (39.2%) of 28 patients with poorly differentiated NETs, the management decision was based on only the 18F-FDG results. For 68Ga-DOTATATE, SUVmax was higher for G1 tumors and lower for G3 tumors (P = 0.012). However, no significant differences in 18F-FDG-derived SUVs were observed between different grades (P = 0.38). The Mann-Whitney test showed significant differences in 68Ga-DOTATATE SUVmax between tumors with a Ki-67 of less than 5% and tumors with a Ki-67 of more than 5% (P = 0.004), without significance differences in 18F-FDG SUVmax Log-rank analysis showed statistically significant differences in survival for patients with bone metastasis versus soft-tissue or no metastasis for both 18F-FDG (P = 0.037) and 68Ga-DOTATATE (P = 0.047). Overall survival declined rapidly with increasing grade (P = 0.001), at an estimated 91 mo for G1, 59 mo for G2, and 48 mo for G3. 18F-FDG PET/CT had no clinical impact on G1 NETs and a moderate impact on G2 NETs. However, in poorly differentiated NETs, 18F-FDG PET/CT plays a significant clinical role in combination with 68Ga-DOTATATE. 68Ga DOTATATE SUVmax relates to grade and Ki-67 and can be used prognostically.

Panagiotidis E ，Alshammari A ，Michopoulou S ，Skoura E ，Naik K ，Maragkoudakis E ，Mohmaduvesh M ，Al-Harbi M ，Belda M ，Caplin ME ，Toumpanakis C ，Bomanji J ... -  《-》

MIB-1 Index-Stratified Assessment of Dual-Tracer PET/CT with (68)Ga-DOTATATE and (18)F-FDG and Multimodality Anatomic Imaging in Metastatic Neuroendocrine Tumors of Unknown Primary in a PRRT Workup Setting.

Our aim was to comparatively assess dual-tracer PET/CT (68Ga-DOTATATE and 18F-FDG) and multimodality anatomic imaging in studying metastatic neuroendocrine tumors (NETs) of unknown primary (CUP-NETs) scheduled for peptide receptor radionuclide therapy for divergence of tracer uptake on dual-tracer PET/CT, detection of primary, and overall lesion detection vis-a-vis tumor proliferation index (MIB-1/Ki-67). Methods: Fifty-one patients with CUP-NETs (25 men, 26 women; age, 22-74 y), histopathologically proven and thoroughly investigated with conventional imaging modalities (ultrasonography, CT/contrast-enhanced CT, MRI, and endoscopic ultrasound, wherever applicable), were retrospectively analyzed. Patients were primarily referred for deciding on feasibility of peptide receptor radionuclide therapy (except 2 patients), and all had undergone 68Ga-DOTATATE and 18F-FDG PET/CT as part of pretreatment workup. The sites of metastases included liver, lung/mediastinum, skeleton, abdominal nodes, and other soft-tissue sites. Patients were divided into 5 groups on the basis of MIB-1/Ki-67 index on a 5-point scale: group I (1%-5%) (n = 35), group II (6%-10%) (n = 8), group III (11%-15%) (n = 4), group IV (16%-20%) (n = 2), and group V (>20%) (n = 2). Semiquantitative analysis of tracer uptake was undertaken by SUVmax of metastatic lesions and the primary (when detected). The SUVmax values were studied over increasing MIB-1/Ki-67 index. The detection sensitivity of 68Ga-DOTATATE for primary and metastatic lesions was assessed and compared with other imaging modalities including 18F-FDG PET/CT. Results: Unknown primary was detected on 68Ga-DOTATATE in 31 of 51 patients, resulting in sensitivity of 60.78% whereas overall lesion detection sensitivity was 96.87%. The overall lesion detection sensitivities (individual groupwise from group I to group V) were 97.75%, 87.5%, 100%, 100%, and 66.67%, respectively. As MIB-1/Ki-67 index increased, 68Ga-DOTATATE uptake decreased in metastatic and primary lesions (mean SUVmax, 43.5 and 22.68 g/dL in group I to 22.54 and 16.83 g/dL in group V, respectively), whereas 18F-FDG uptake showed a gradual rise (mean SUVmax, 3.66 and 2.86 g/dL in group I to 7.53 and 9.58 g/dL in group V, respectively). There was a corresponding decrease in the 68Ga-DOTATATE-to-18F-FDG uptake ratio with increasing MIB-1/Ki-67 index (from 11.89 in group I to 2.99 in group V). Conclusion: In CUP-NETs, the pattern of uptake on dual-tracer PET (68Ga-DOTATATE and 18F-FDG) correlates well with tumor proliferation index with a few outliers; combined dual-tracer PET/CT with MIB-1/Ki-67 index would aid in better whole-body assessment of tumor biology in CUP-NETs.

Sampathirao N ，Basu S 《-》

Can complementary 68Ga-DOTATATE and 18F-FDG PET/CT establish the missing link between histopathology and therapeutic approach in gastroenteropancreatic neuroendocrine tumors?

Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are indolent neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. Tumor size, existence of metastasis, and histopathologic classification remain incapable in terms of treatment decision and prognosis estimation. This study aimed to compare (68)Ga-DOTATATE and (18)F-FDG PET/CT in GEPNETs and to investigate the relation between the complementary PET/CT results and histopathologic findings in the management of therapy, particularly in intermediate-grade patients. The relation between complementary (68)Ga-DOTATATE and (18)F-FDG PET/CT results of 27 GEPNET patients (mean age, 56 y; age range, 33-79 y) and histopathologic findings was evaluated according to grade and localization using standardized maximum uptake values and Ki67 indices. Grade 2 (G2) patients were further evaluated in 2 groups as G2a (3%-9%) and G2b (10%-20%) according to Ki67 indices. The sensitivity of (68)Ga-DOTATATE and (18)F-FDG PET/CT was 95% and 37%, respectively, and the positive predictive values were 93.8% and 36.2%, respectively. The sensitivity in detecting liver metastasis, lymph nodes, bone metastasis, and primary lesion was 95%, 95%, 90%, and 93% for (68)Ga-DOTATATE and 40%, 28%, 28%, and 75% for (18)F-FDG, respectively. Statistically significant differences were found between grades 1-2, 2a-2b, and 1-2b with respect to (68)Ga-DOTATATE PET/CT as well as between 1-2a and 1-2b with respect to (18)F-FDG PET/CT. However, no statistical differences were found between 1 and 2a (P > 0.05) for (68)Ga-DOTATATE and 2a and 2b (P = 0.484) for (18)F-FDG. The impact of the combined (18)F-FDG and (68)Ga-DOTATATE PET/CT on the therapeutic decision was 59%. Combined (68)Ga-DOTATATE and (18)F-FDG PET/CT is helpful in the individual therapeutic approach of GEPNETs and can overcome the shortcomings of histopathologic grading especially in intermediate-grade GEPNETs.

Has Simsek D ，Kuyumcu S ，Turkmen C ，Sanlı Y ，Aykan F ，Unal S ，Adalet I ... -  《-》

Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG.

The aim was to assess the relevant distribution of the novel PET tracer (68)Ga-DOTATATE in neuroendocrine tumors (NETs) with combined positron emission tomography / computed tomography (PET/CT) and compare its performance with that of (18)F-FDG PET/CT. The imaging findings with (68)Ga-DOTATATE and (18)F-FDG on 38 consecutive patients with a diagnosis of primary or recurrent NET were compared and correlated with tumor grade on histology based on ki67 and mitotic index. The sensitivity of (68)Ga-DOTATATE PET/CT was 82% (31 of 38) and that of (18)F-FDG PET/CT was 66% (25 of 38). The sensitivity of combined (68)Ga-DOTATATE and (18)F-FDG PET/CT was 92% (35 of 38). There was greater uptake of (68)Ga-DOTATATE than (18)F-FDG in low-grade NET (median SUV 29 vs 2.9, P < .001). In high-grade NET there was higher uptake of (18)F-FDG over (68)Ga-DOTATATE (median SUV 11.7 vs 4.4, P = .03). There was a significant correlation with predominant tumor uptake of (68)Ga-DOTATATE or (18)F-FDG and tumor grade on histology (P < .0001). (68)Ga-DOTATATE PET/CT is a useful novel imaging modality for NETs and is superior to (18)F-FDG for imaging well-differentiated NET. Functional imaging with both (68)Ga-DOTATATE and (18)F-FDG has potential for a more comprehensive tumor assessment in intermediate- and high-grade tumors.

Kayani I ，Bomanji JB ，Groves A ，Conway G ，Gacinovic S ，Win T ，Dickson J ，Caplin M ，Ell PJ ... -  《-》

Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors.

Wild D ，Bomanji JB ，Benkert P ，Maecke H ，Ell PJ ，Reubi JC ，Caplin ME ... -  《-》