Pretherapeutic Comparative Dosimetry of<sup>177</sup>Lu-rhPSMA-7.3 and<sup>177</sup>Lu-PSMA I&T in Patients with Metastatic Castration-Resistant Prostate Cancer
Benedikt Feuerecker, Maythinee Chantadisai, Anne Allmann, Robert Tauber, Jakob Allmann, Lisa Steinhelfer, Isabel Rauscher, Alexander Wurzer, Hans‐Jürgen Wester, Wolfgang Weber, Calogero D’Alessandria, Matthias Eiber
Abstract
Introduction: Radiohybrid prostate-specific membrane antigen (rhPSMA)-ligands allow for labelling with <sup>18</sup>F and radiometals for endoradiotherapy. rhPSMA-7.3 is designated as lead compound with promising preclinical data for <sup>177</sup>Lu-rhPSMA-7.3 indicating higher tumor uptake compared with <sup>177</sup>Lu-PSMA-I&T. In this retrospective analysis we compared pre-therapeutic clinical dosimetry of both PSMA-ligands. <b>Methods:</b> Six mCRPC patients underwent both <sup>177</sup>Lu-rhPSMA-7.3 and <sup>177</sup>Lu-PSMA-I&T pre-therapeutic dosimetry. Whole-body scintigraphy was performed at 1h, 4h, 24h, 48h and 7d post injection. Regions of interest (ROI) covering the whole body, organs, bone marrow and tumor lesions per patient were drawn. Absorbed doses for individual patients and pre-therapeutic applications were calculated using OLINDA/EXM. To facilitate comparison of both ligands we introduced the therapeutic index (TI) defined as ratio of mean pre-therapeutic doses to tumor lesions over relevant organs-at-risk. <b>Results:</b> Mean whole-body pre-therapeutic effective doses were 0.12±0.07 vs. 0.05±0.03 Sv/GBq and mean absorbed organ doses were e.g. 1.65±0.28 vs. 0.73±0.18 Gy/GBq for the kidneys; 0.19±0.09 vs. 0.07±0.03 Gy/GBq for the liver and 2.35±0.78 vs. 0.80±0.41 Gy/GBq for the parotid, for the bone marrow 0.67±0.62 vs. 0.30±0.27 Gy/GBq for <sup>177</sup>Lu-rhPSMA-7.3 vs. <sup>177</sup>Lu-PSMA-I&T, respectively. Tumor lesions received a mean absorbed doses of 6.44±6.44 vs. 2.64±2.24 Gy/GBq for <sup>177</sup>Lu-rhPSMA-7.3 vs. <sup>177</sup>Lu-PSMA-I&T, respectively. The mean TI(kidney) and TI(bone_marrow) were 3.7±2.2 vs. 3.6±2.2 and 15.2±10.2 vs. 15.1±10.2, for <sup>177</sup>Lu-rhPSMA-7.3 vs. <sup>177</sup>Lu-PSMA-I&T, respectively. <b>Conclusion:</b> Pre-therapeutic clinical dosimetry confirmed preclinical results with 2-3 times higher mean absorbed doses for tumors of <sup>177</sup>Lu-rhPSMA-7.3 compared to <sup>177</sup>Lu-PSMA-I&T. Absorbed doses to normal organs also tended to be higher for <sup>177</sup>Lu-rhPSMA-7.3 resulting overall in a similar average TI for both radiopharmaceuticals with considerable inter-patient variability. <sup>177</sup>Lu-rhPSMA-7.3 holds promise for similar therapeutic efficacy as <sup>177</sup>Lu-PSMA-I&T at lower amounts of injected activity simplifying radiation safety measurements (especially for large patient numbers and/or dose escalation regimes).