Lesion Quantification Accuracy of Digital 90Y PET Imaging in the Context of Dosimetry in Systemic Fibroblast Activation Protein Inhibitor Radionuclide Therapy

Abstract

Therapy with ⁹⁰Y-labeled fibroblast activation protein inhibitors (⁹⁰Y-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 ⁹⁰Y 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 ⁹⁰Y-FAPI therapy. The aim of this study was to explore the conditions for reliable lesion image quantification in ⁹⁰Y-FAPI radionuclide therapy using a digital PET/CT system. Methods: Two tumor phantoms were filled with ⁹⁰Y 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 ⁹⁰Y-FAPI is presented to project the phantom results to clinical scenarios. Results: 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. Conclusion: For lesion sizes and activity concentrations that are expected to be observed in patients treated with ⁹⁰Y-FAPI, quantification with reasonable accuracy is possible. Further dosimetry studies are needed to thoroughly investigate the efficacy and safety of ⁹⁰Y-FAPI therapy.

Keywords: 90Y; FAPI therapy; PET; minimum detectable activity; quantification accuracy.