(⁶⁸Ga) Ga-DOTA.SA.FAPi PET/CT in the assessment of WHO grade 3 Neuro-endocrine tumors

Minimal or lack of somatostatin receptor (SSTR) expression with a high (¹⁸F)F-FDG avidity is a characteristic of grade 3 neuroendocrine tumors (NETs) and an independent prognostic factor associated with an increased risk of death. For patients who are (¹⁸F)F-FDG positive but SSTR PET negative, the disease cannot be effectively targeted with either octreotide or PRRT. Hence, newer theranostic molecular probes are crucial for opening new targeted therapeutic options in aggressive NETs. Cancer-associated fibroblasts (CAF)-related markers such as fibroblast activation proteins (FAP) are potential alternate therapeutic targets for aggressive NETs. The study aimed to study the diagnostic performance (⁶⁸Ga)Ga-DOTA.SA.FAPi and compare the results with (⁶⁸Ga)Ga-DOTANOC and (¹⁸F)F-FDG PET/CT findings. Fifteen patients (11 males and 4 women; mean age: 40.8 ± 16 years) with histologically confirmed grade 3 NETs were enrolled and underwent (⁶⁸Ga) Ga-DOTA.SA.FAPi, (⁶⁸Ga) Ga-DOTANOC, and (¹⁸F)F-FDG PET/CT scans. The quantitative assessment included comparing standardized uptake values corrected for lean body mass (SULpeak and SULavg). Findings on both the scans were validated with diagnostic computed tomography. Fifteen patients had five types of NETs: pancreatic NET in five, mesenteric NET in one, carcinoids in seven, ovarian NET in 1, and NET appendix in 1 patient, respectively. (⁶⁸Ga) Ga-DOTA.SA.FAPi demonstrated a significantly higher uptake for all the primary lesions (SULpeak 14.1 vs 3.6, p-0.0078), lymph nodes SULpeak (8.68 vs 4.1, p-0.0159), bone (SULpeak 9.3 vs 2.8, p-0.0001), and liver metastases (SULpeak 8.3 vs 4.8, p-0.0033) compared to (⁶⁸Ga) Ga-DOTANOC. (⁶⁸Ga)Ga-DOTA.SA.FAPi PET/CT imaging is a promising new imaging modality in (⁶⁸Ga)Ga-DOTANOC negative, (¹⁸F)F-FDG positive NETs. It has the potential to open a new avenue for treatment of high grade NETs. (author)