Head-to-head comparison of [68Ga]Ga-DOTA.SA.FAPi with [18F]F-FDG PET/CT in radioiodine-resistant follicular-cell derived thyroid cancers

Abstract

Purpose: In the context of radioiodine-resistant follicular-cell derived thyroid cancers (RAI-R-FCTC), [¹⁸F]F-FDG PET/CT serves as a widely used and valuable diagnostic imaging method. However, there is growing interest in utilizing molecular imaging probes that target cancer-associated fibroblasts (CAFs) as an alternative approach. This study sought to compare the diagnostic capabilities of [⁶⁸Ga]Ga-DOTA.SA.FAPi and [¹⁸F]F-FDG PET/CT in patients with RAI-R-FCTC.

Methods: In this retrospective study, a total of 117 patients with RAI-R-FCTC were included. The study population consisted of 68 females and 49 males, with a mean age of 53.2 ± 11.7 years. The aim of the study was to perform a comprehensive qualitative and quantitative assessment of [⁶⁸Ga]Ga-DOTA.SA.FAPi and [¹⁸F]F-FDG PET/CT scans in RAI-R-FCTC patients. The qualitative assessment involved comparing patient-based and lesion-based visual interpretations of both scans, while the quantitative assessment included analyzing standardized uptake values corrected for lean body mass (SULpeak and SULavg). The findings obtained from the scans were validated by correlating them with morphological findings from diagnostic computed tomography and/or histopathological examination.

Results: Among the 117 RAI-R-FCTC patients, 60 had unilateral local disease, and 9 had bilateral lesions with complete concordance in the detection rate on both PET scans. [⁶⁸Ga]Ga-DOTA.SA.FAPi had a higher detection rate for lymph nodes (95.4% vs 86.6%, p<0.0001), liver metastases (100% vs. 81.3%, p<0.0001), and brain metastases (100% vs. 39%, p<0.0001) compared to [¹⁸F]F-FDG. The detection rates for pleural and bone metastases were similar between the two radiotracers. For lung metastases, [⁶⁸Ga]Ga-DOTA.SA.FAPi showed a detection rate of 81.7%, whereas [¹⁸F]F-FDG had a detection rate of 64.6%. Remarkably, [⁶⁸Ga]Ga-DOTA.SA.FAPi was able to detect a bowel metastasis that was missed on [¹⁸F]F-FDG scan. The median standardized uptake values (SUL) were generally comparable between the two radiotracers, except for brain metastases (SULpeak [⁶⁸Ga]Ga-DOTA.SA.FAPi vs. [¹⁸F]F-FDG: 13.9 vs. 6.7, p-0.0001) and muscle metastases (SULpeak [⁶⁸Ga]Ga-DOTA.SA.FAPi vs. [¹⁸F]F-FDG: 9.56 vs. 5.62, p-0.0085), where [⁶⁸Ga]Ga-DOTA.SA.FAPi exhibited higher uptake.

Conclusion: The study results demonstrate the superior performance of [⁶⁸Ga]Ga-DOTA.SA.FAPi compared to [¹⁸F]F-FDG PET/CT in detecting lymph nodal, liver, bowel, and brain metastases in patients with RAI-R-FCTC. These findings highlight the potential of [⁶⁸Ga]Ga-DOTA.SA.FAPi as a theranostic tool that can complement the benefits of [¹⁸F]F-FDG PET/CT in the imaging of RAI-R-FCTC.

Keywords: Radioiodine-resistant follicular-cell derived thyroid cancer; [18F]F-FDG; [68Ga]Ga-DOTA.SA.FAPi.