Dual PET Imaging with [68Ga]Ga-DOTA-TOC and [18F]FDG to Localize Neuroendocrine Tumors of Unknown Origin

Neuroendocrine tumors of unknown primary (CUP-NET) present a diagnostic challenge when conventional imaging fails to localize the primary tumor. This study aimed to evaluate the diagnostic value of concurrent [⁶⁸Ga]Ga-DOTA-TOC and [¹⁸F]FDG PET/CT imaging in localizing primary tumors in patients with histologically confirmed CUP-NET. Thirty-four patients underwent both imaging modalities as part of a prospective imaging protocol after negative conventional imaging or [¹¹¹In]In-octreotide scintigraphy. Primary tumor detection rates were assessed, and imaging characteristics compared between the two modalities. The overall localization rate was 58.9% (20/34). Of these, 90% (18/20) of primary tumors were identified solely by [⁶⁸Ga]Ga-DOTA-TOC PET/CT, with the remaining two visualized by both modalities. [¹⁸F]FDG PET/CT did not independently localize any primary tumors. Identified primaries were limited to grade 1 (60%) or grade 2 (40%) tumors, predominantly in the small intestine (95%). Among localized cases, 45% (9/20) underwent surgical resection and 15% (3/20) became eligible for peptide receptor radionuclide therapy. [⁶⁸Ga]Ga-DOTA-TOC PET/CT demonstrated superior detection of metastatic lesions compared to [¹⁸F]FDG PET/CT (97.1% vs. 70.6%, <i>p</i> = 0.006). No significant survival differences were observed between patients with localized versus non-localized primaries. These findings support the value of [⁶⁸Ga]Ga-DOTA-TOC PET/CT for identifying primary tumors in CUP-NET. Further research is warranted to explore the role of [¹⁸F]FDG PET/CT in high-grade NETs.