Lesion Quantification Accuracy of Digital Y PET Imaging in the Context of Dosimetry in Systemic Fibroblast Activation Protein Inhibitor Radionuclide Therapy.

Therapy with Y-labeled fibroblast activation protein inhibitors (Y-FAPIs) was recently introduced as a novel treatment concept for patients with solid tumors. Lesion and organ-at-risk dosimetry is part of assessing treatment efficacy and safety and requires reliable quantification of tissue uptake. As Y quantification is limited by the low internal positron-electron pair conversion rate, the increased effective sensitivity of digital silicon photomultiplier-based PET/CT systems might increase quantification accuracy and, consequently, allow for dosimetry in Y-FAPI therapy. The aim of this study was to explore the conditions for reliable lesion image quantification in Y-FAPI radionuclide therapy using a digital PET/CT system. Two tumor phantoms were filled with Y solution using different sphere activity concentrations and a constant signal-to-background ratio of 40. The minimum detectable activity concentration was determined, and its dependence on acquisition time (15 vs. 30 min per bed position) and smoothing levels (all-pass vs. 5-mm gaussian filter) was investigated. Quantification accuracy was evaluated at various activity concentrations to estimate the minimum quantifiable activity concentration using contour-based and oversized volume-of-interest-based quantification approaches. A ±20% deviation range between image-derived and true activity concentrations was regarded as acceptable. Tumor dosimetry for 3 patients treated with Y-FAPI is presented to project the phantom results to clinical scenarios. For a lesion size of 40 mm and a clinical acquisition time of 15 min, both minimum detectable and minimum quantifiable activity concentrations were 0.12 MBq/mL. For lesion sizes of greater than or equal to 30 mm, accurate quantification was feasible for detectable lesions. Only for the smallest 10-mm sphere, the minimum detectable and minimum quantifiable activity concentrations differ substantially (0.43 vs. 1.97 MBq/mL). No notable differences between the 2 quantification approaches were observed. For the investigated tumors, absorbed dose estimates with reliable accuracy were achievable. For lesion sizes and activity concentrations that are expected to be observed in patients treated with Y-FAPI, quantification with reasonable accuracy is possible. Further dosimetry studies are needed to thoroughly investigate the efficacy and safety of Y-FAPI therapy.