Head-to-Head Comparison of [ 68 Ga]Ga-DOTA.SA.FAPi and [ 68 Ga]Ga-DOTANOC Positron Emission Tomography/Computed Tomography Imaging for the Follow-Up Surveillance of Patients with Medullary Thyroid Cancer.

Background: A theranostic probe for accurate staging and treatment is crucial for the management of medullary thyroid cancers (MTCs). The abundance of stroma in most of thyroid cancers, including MTC, opens new avenues for selecting cancer-associated fibroblasts (CAFs) as new molecular imaging and therapeutic targets. [68 Ga]Ga-labeled fibroblast activation protein inhibitor (FAPi) molecules have gained importance as alternative molecular imaging agents in the imaging of thyroid cancers. The purpose of this study was to compare the detection efficiency of primary and metastatic lesions of MTCs between [68 Ga]Ga-DOTA.SA.FAPi and [68 Ga]Ga-DOTANOC positron emission tomography (PET) radiotracers. Materials and Methods: In this retrospective study, [68 Ga]Ga-DOTANOC and [68 Ga]Ga-DOTA.SA.FAPi PET/CT (computed tomography) images were compared using patient-based and lesion-based analysis in patients with MTC for follow-up assessment. The quantitative assessment included comparing standardized uptake values corrected for lean body mass (SULpeak) and tumor-to-background ratios (TBR). The findings on both scans were validated with the morphological findings of the diagnostic CT. Results: Twenty-seven patients (21 males and 6 females) with a mean age of 42.4 ± 13.2 years (range 14-66 years) were included in the study. [68 Ga]Ga-DOTA.SA.FAPi had similar sensitivities as that of [68 Ga]Ga-DOTANOC PET/CT for detecting primary tumors (100% [18 of 18] vs. 94.4% [17 of 18], p  = 0.979) involved lymph nodes (98.3% [118 of 120] vs. 95% [114 of 120], p  = 0.288), and brain metastases (100%). [68 Ga]Ga-DOTA.SA.FAPi demonstrated significantly higher sensitivities than [68 Ga]Ga-DOTANOC PET/CT for detecting lung nodules (93.5% [87 of 93] vs. 68.9% [64 of 93], p  < 0.0001), liver (100% [105 of 105] vs. 46.4% [49 of 105], p  < 0.0001), bone (92.4% [110 of 119] vs. 76.5% [91 of 119], p  = 0.001), and pleural metastases 98.2% versus 0%. Higher uptake values and TBR values were reported with [68 Ga]Ga-DOTA.SA.FAPi compared with that of [68 Ga]Ga-DOTANOC. Conclusion: [68 Ga]Ga-DOTA.SA.FAPi outperformed [68 Ga]Ga-DOTANOC PET/CT in the detection of distant metastases with both patient-based and lesion-based analysis in MTCs.