Abstract
Aim: Comparative assessment of dual tracer PET/CT (68Ga-DOTATATE and 18F-FDG) and multimodality anatomical imaging in studying CUP-NETs scheduled for PRRT for: (i) divergence of tracer uptake on dual tracer PET/CT, (ii) detection of primary and (iii) overall lesion detection vis-a-vis tumor proliferation index (Mib1/Ki-67). Materials and Methods: Fifty-one patients of CUP-NETs (M:F=25:26, age:22-74 years), histopathologically proven and thoroughly investigated with conventional imaging modalities (USG, CT/ceCT, MRI and EUS, wherever applicable), were retrospective analyzed. They were primarily referred for deciding on feasibility of PRRT (except 2 patients) and all had undergone 68Ga-DOTATATE and 18F-FDG PET/CT as part of pre-treatment work up. The sites of metastases included liver, lung/mediastinum, skeleton, abdominal nodes and other soft tissue sites. Patients were divided into 5 groups based on Mib1/Ki-67 index of 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), 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 Mib1/Ki67 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 31/51 patients resulting in sensitivity of 60.78% while overall lesion detection sensitivity was 96.87%. The overall lesion detection sensitivities (individual group-wise from Group I to Group V) were 97.75%, 87.5%, 100%, 100% and 66.67% respectively. As Mib1/Ki67 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), while 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 corresponding decrease in 68Ga-DOTATATE/18F-FDG uptake ratio with increasing Mib1/Ki-67 index (from 11.89 in group I to 2.99 in group V). Conclusion: In CUP-NETs, pattern of uptake on dual tracer PET (68Ga-DOTATATE/18F-FDG) correlates well with tumor proliferation index with a few outliers; combined dual tracer PET/CT with Mib1/Ki-67 index would aid in better whole-body assessment of tumour biology in CUP-NETs.
