Very low rate of humoral response after a third COVID-19 vaccine dose in patients with autoimmune diseases treated with rituximab and non-responders to two doses

⁹⁰Y-FAPI therapy was recently introduced as 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, due to improved time-of-flight resolution, 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 dependency from acquisition time (15 min vs. 30 min per bed) and smoothing levels (all-pass vs. 5-mm Gaussian filter) was investigated. Quantification accuracy was evaluated at varying activity concentrations to estimate the minimum quantifiable activity concentration based on a contour- and an oversize-based quantification approach. A ±20% deviation range between imaged-derived and true activity concentrations was regarded acceptable. Tumor dosimetry of three ⁹⁰Y-FAPI therapy patients 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 ≥30 mm, accurate quantification was feasible for detectable lesions. Only for the smallest 10-mm sphere, minimum detectable and minimum quantifiable activity concentration differed substantially (0.43 vs. 1.97 MBq/mL). No notable differences between the two quantification approaches were observed. For the investigated tumors, absorbed dose estimates with a reliable accuracy were achievable. Conclusion: For lesion sizes and activity concentrations that are expected to be observed in ⁹⁰Y-FAPI patients, quantification with reasonable accuracy is possible. Further dosimetry studies are needed to thoroughly investigate efficacy and safety of ⁹⁰Y-FAPI therapy.