MIB-1 Index-Stratified Assessment of Dual-Tracer PET/CT with Ga-DOTATATE and 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 (Ga-DOTATATE and F-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). 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 Ga-DOTATATE and F-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%) ( = 35), group II (6%-10%) ( = 8), group III (11%-15%) ( = 4), group IV (16%-20%) ( = 2), and group V (>20%) ( = 2). Semiquantitative analysis of tracer uptake was undertaken by SUV of metastatic lesions and the primary (when detected). The SUV values were studied over increasing MIB-1/Ki-67 index. The detection sensitivity of Ga-DOTATATE for primary and metastatic lesions was assessed and compared with other imaging modalities including F-FDG PET/CT. Unknown primary was detected on Ga-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, Ga-DOTATATE uptake decreased in metastatic and primary lesions (mean SUV, 43.5 and 22.68 g/dL in group I to 22.54 and 16.83 g/dL in group V, respectively), whereas F-FDG uptake showed a gradual rise (mean SUV, 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 Ga-DOTATATE-to-F-FDG uptake ratio with increasing MIB-1/Ki-67 index (from 11.89 in group I to 2.99 in group V). In CUP-NETs, the pattern of uptake on dual-tracer PET (Ga-DOTATATE and F-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.