Predicting [⁹⁰Y]Y-FAPI-46 Tumor Absorbed Dose from Single-Time-Point [⁶⁸Ga]Ga-FAPI-46 PET/CT Imaging

Radiolabeled fibroblast activation protein (FAP)-targeting peptides, such as ⁹⁰Y-FAPI-46, have increasingly been used to treat various tumor entities, with preliminary reports indicating therapeutic responses with acceptable toxicity profiles. Dosimetry can be used to maximize antitumor capability and minimize side effects. The aim of this study was to investigate whether ⁹⁰Y-FAPI-46 tumor dosimetry can be predicted by diagnostic ⁶⁸Ga-FAPI-46 PET/CT data. Methods: Fourteen patients with 24 lesions underwent a single-time-point ⁶⁸Ga-FAPI-46 PET/CT scan and 3 ⁹⁰Y-FAPI-46 PET/CT scans for dosimetry within a 3-mo interval. Tumors were identified on PET images, and the anatomic tumor volume was measured on low-dose CT. Tumor uptake extrapolated at time of injection, time-integrated activity coefficient (TIAC), and tumor absorbed dose were calculated as reference values using ⁹⁰Y-FAPI-46 data and compared with the corresponding predicted values using ⁶⁸Ga-FAPI-46 data by means of a single-time-point dosimetry model. Correlations between ⁹⁰Y-FAPI-46- and ⁶⁸Ga-FAPI-46-based values were assessed. Results: In calculating the predicted values using a single-time-point ⁶⁸Ga-FAPI-46 PET/CT, the mean effective half-life of ⁹⁰Y-FAPI-46 across all lesions was 8.44 ± 1.73 h. The mean ± SD ratio (i.e., the predicted values using ⁶⁸Ga-FAPI-46 data divided by the reference ⁹⁰Y-FAPI-46 data) were 0.93 ± 0.39, 0.77 ± 0.35, and 0.77 ± 0.35 for tumor uptake, TIAC, and tumor absorbed dose, respectively. In the Bland-Altman analysis, mean differences (bias) ± SD of the percent differences of tumor uptake, TIAC, and tumor absorbed dose were -16.11% ± 43.28% (95% CI, -100.90 to 68.73%; Spearman ρ = 0.91; P < 0.0001), -32.60% ± 41.26% (95% CI, -113.50 to 48.26%; Spearman ρ = 0.91; P < 0.0001), and -33.35% ± 40.19% (95% CI, -112.10 to 45.43%; Spearman ρ = 0.77; P < 0.0001), respectively. Conclusion: Tumor uptake, TIAC, and tumor absorbed dose on ⁹⁰Y-FAPI-46 PET/CT and ⁶⁸Ga-FAPI-46 PET/CT were highly correlated, although the values on ⁶⁸Ga-FAPI-46 PET/CT tended to be lower than those on ⁹⁰Y-FAPI-46 PET/CT. Predicted values on ⁶⁸Ga-FAPI-46 PET/CT can help clinicians with diagnostic stratification and patient selection, with intratherapeutic verification remaining necessary before any individualization of administered activity.