FAP-targeted [⁶⁸Ga]BED003-PET in different solid malignancies.

Abstract

PURPOSE: Positron emission tomography (PET) using fibroblast activation protein inhibitors (FAPI) has emerged as a robust imaging tool for solid tumours. The novel ligand [68Ga]BED003 (formerly known as [68Ga]Ga-OncoFAP-DOTAGA) has demonstrated very high affinity for the fibroblast activation protein and favourable biodistribution. This study aimed to assess the in vivo distribution of [68Ga]BED003 across a spectrum of solid tumours as a potential prerequisite for radioligand therapy. METHODS: In this retrospective analysis, [68Ga]BED003 PET/CT or PET/MRI of 157 patients with 19 different solid malignancies were retrospectively analysed. A spherical volume of interest (VOI) was placed over the primary tumour, the most intense lymph node and distant metastases that were evaluated as at least likely malignant in the written reports, and the maximum standardized uptake value (SUVmax) was derived. Liver and blood pool background mean SUV (SUVmean) were assessed using standardised VOIs. Tumour-to-background ratios (TBRmax) were calculated as the ratio of SUVmax to background SUVmean. SUVmax and TBRmax values of primary tumours, lymph node, and distant metastases were compared using Wilcoxon rank-sum and signed-rank tests, as appropriate. RESULTS: Overall, 115 primary tumours, 70 lymph node metastases, and 116 distant metastases were analysed, yielding median SUVmax of 16.6, 12.3, and 11.9, respectively. No significant difference in SUVmax or TBRmax were observed between lymph node and distant metastases (all P > 0.05). In contrast, primary tumours demonstrated significantly higher uptake than lymph node and distant metastases (all P < 0.001), except for liver TBRmax when comparing primary tumours with lymph node metastases (P > 0.05). Across all 301 lesions, the median SUVmax, liver TBRmax and blood pool TBRmax was 14.7 (range, 4.2–35.9), 21.6 (range, 4.2–62.8) and 11.1 (range, 3.0–33.4), respectively. The highest median SUVmax and TBRmax (both) in cohorts with > 5 lesions were found in medullary thyroid, oesophageal, ovarian, cervical, breast, colorectal, and hepatocellular cancers. CONCLUSION: [68Ga]BED003-PET demonstrated consistently high uptake across diverse solid malignancies, supporting its potential role as a tool for multi-cancer diagnostic imaging and patient selection for FAP-targeted radioligand therapy.