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
Samuel Bitoun, Jérôme Avouac, Julien Henry, R. Ghossan, Omar Al Tabaa, Rakiba Belkhir, Gaëtane Nocturne, Alice Andrée Mariaggi, Flore Rozenberg, Christelle Vauloup‐Fellous, Xavier Mariette, Raphaèle Séror
Abstract
<sup>90</sup>Y-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 <sup>90</sup>Y 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 <sup>90</sup>Y-FAPI therapy. The aim of this study was to explore the conditions for reliable lesion image quantification in <sup>90</sup>Y-FAPI radionuclide therapy using a digital PET/CT system. <b>Methods:</b> Two tumor phantoms were filled with <sup>90</sup>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 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 <sup>90</sup>Y-FAPI therapy patients is presented to project the phantom results to clinical scenarios. <b>Results:</b> 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. <b>Conclusion:</b> For lesion sizes and activity concentrations that are expected to be observed in <sup>90</sup>Y-FAPI patients, quantification with reasonable accuracy is possible. Further dosimetry studies are needed to thoroughly investigate efficacy and safety of <sup>90</sup>Y-FAPI therapy.