Predicting [ 90 Y]Y-FAPI-46 Tumor Absorbed Dose from Single-Time-Point [ 68 Ga]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.