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

Abstract

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 SUV_max of metastatic lesions and the primary (when detected). The SUV_max 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 SUV_max, 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 SUV_max, 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.

Keywords: 18F-FDG PET/CT; 68Ga-DOTATATE PET/CT; metastatic NET of unknown primary (CUP-NET); neuroendocrine tumor.