FAP-targeted [68Ga]BED003-PET compared with [18F]DOPA-PET in patients with recurrent medullary thyroid carcinoma

Abstract

Molecular imaging of recurrent or advanced medullary thyroid carcinoma (MTC) remains clinically challenging. [ 18 F]DOPA-PET is an established reference standard, but its sensitivity is limited and dependent on tumour burden and biomarker levels. Fibroblast activation protein (FAP)-targeted PET has emerged as a promising imaging approach across several malignancies. This study aimed to compare the detection rate and quantitative imaging characteristics of [ 68 Ga]BED003-PET, recently known as [ 68 Ga]OncoFAP-DOTAGA, with [ 18 F]DOPA-PET in patients with recurrent or advanced MTC. Eight patients with histologically proven MTC and suspected recurrence or progression based on elevated calcitonin levels underwent both [ 18 F]DOPA-PET and an additional [ 68 Ga]BED003-PET. All patients presented with inconclusive findings in [ 18 F]DOPA-PET. Comparative analyses were performed on a patient- and lesion-based level. Quantitative parameters included maximum and mean standardized uptake values (SUV max /SUV mean ), metabolic tumour volume (MTV), and maximum tumour-to-background ratios (TBR max ). Potential theranostic suitability was explored based on lesional FAP uptake. The median interval between PET acquisitions was 33 days (range, 7–56 days). In total, 35 tracer-avid lesions were detected. [ 68 Ga]BED003-PET detected significantly more lesions than [ 18 F]DOPA-PET (34/35 [97%] vs. 16/35 [46%], P  < 0.001). 15 lesions (43%) were positive on both modalities, 19 (54%) were only [ 68 Ga]BED003-positive, and 1 (2.9%) was only [ 18 F]DOPA-positive. Quantitative analysis demonstrated significantly higher uptake and contrast for [ 68 Ga]BED003, including higher blood-pool TBRmax than [ 18 F]DOPA (6.02 vs. 2.23, Bonferroni adjusted P  < 0.001). In this small MTC cohort, [ 68 Ga]BED003-PET demonstrated higher lesion detection and TBRs in patients with inconsistent findings in [ 18 F]DOPA-PET. Prospective multicenter validation is warranted.