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 (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 andF-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 includingF-FDG PET/CT. Unknown primary was detected onGa-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.

Classification of pulmonary neuroendocrine tumors: new insights

“…However, differences in cell lineage or the diverse application of defining criteria may cause some inconsistency to arise in the diagnostic, prognostic and predictive interpretation (8)(9)(10)(11). This bewildering situation becomes even more challenging and frustrating when dealing with metastatic NENs of unproven or uncertain origin and/or small-sized diagnostic material, where morphology alone may be a major pitfall in the management of tumor patients (5,(30)(31)(32)(33)(34)(35)(36).…”

Diagnostic Approaches to Neuroendocrine Neoplasms of Unknown Primary Site

“…FDG-PET has a diagnostic role in NENs of unknown primary with a higher proliferation index, as uptake has been shown to rise with Ki67 as 68Ga-DOTATATE PET uptake reduces [55]. Abgral et al [56] showed FDG-PET to have an 88% sensitivity in detecting the primary in a series of NENs with Ki67 > 10%, higher than that of SRS in the same study.…”

Peptide Receptor Radionuclide Therapy in the Management of Neuroendocrine Tumors (Neoplasms): Fundamentals and Salient Clinical Practice Points for Medical Oncologists

“…The relative uptake of 68 Ga-DOTATATE and FDG in the tumor has evolved as a powerful indicator of assessing the dynamic tumor biology of NENs on a continuous scale. [15][16][17][18] This parameter has been well recognized in most active PRRT centers, and the medical oncologists at our setup are quite accustomed to interpretation of these studies. Along with the tumor Ki-67/MIB-1, 68 Ga-DOTATATE/FDG relative uptake forms an additional parameter to depict the tumor phenotype.…”

“…Thus, areas where this can be of potential help in deciphering the tumor biology are: (i) tumors in the intermediate level of Ki-67 LI, for example, 10%-20%; (ii) tumors with Ki-67 LI between 20% and 30% (plays important and robust role for deciding between PRRT, chemo-PRRT, and chemotherapy); and (iii) cases showing discordance between Ki-67 and the dual-tracer PET-CT findings. [15,16]…”