MIB-1 Index-Stratified Assessment of Dual-Tracer PET/CT with68Ga-DOTATATE and18F-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 and18F-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 undergone68Ga-DOTATATE and18F-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 SUVmaxof metastatic lesions and the primary (when detected). The SUVmaxvalues were studied over increasing MIB-1/Ki-67 index. The detection sensitivity of68Ga-DOTATATE for primary and metastatic lesions was assessed and compared with other imaging modalities including18F-FDG PET/CT.Results:Unknown primary was detected on68Ga-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), whereas18F-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 the68Ga-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 and18F-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.
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Parel, Mumbai.
Nikita
N
Sampathirao
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Parel, Mumbai drsanb@yahoo.com.
Sandip
S
Basu
D000328:Adult; D000368:Aged; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy / Q000556:secondary*; D009942:Organometallic Compounds; D000072078:Positron Emission Tomography Computed Tomography; D011849:Radioactive Tracers; D017481:Receptors, Somatostatin / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
D019394:Ki-67 Antigen; D009942:Organometallic Compounds; D011849:Radioactive Tracers; D017481:Receptors, Somatostatin; D019788:Fluorodeoxyglucose F18; C513399:gallium Ga 68 dotatate
18F-FDG PET/CT; 68Ga-DOTATATE PET/CT; metastatic NET of unknown primary (CUP-NET); neuroendocrine tumor