Nikita Sampathirao1, Sandip Basu2. 1. Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Parel, Mumbai. 2. Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Parel, Mumbai drsanb@yahoo.com.
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 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.
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.