225Ac-NOTA-trastuzumab human dosimetry using inter-radionuclide and biological half-life based allometric extrapolation method.

BACKGROUND: Image-based dosimetry of 225Ac is challenging due to its high cytotoxicity, which limits the administered dose and, consequently, restricts the number of photons available for imaging. This study aimed to estimate human equivalent dose of 225Ac-NOTA-trastuzumab while considering dose contribution from daughter radionuclides using mouse biodistribution of 64Cu-NOTA-trastuzumab by utilizing a combined model of mouse-to-human extrapolation and Bateman equation. RESULTS: Residence times estimated by methods M3, which involved mouse residence times and biological half-life allometry was significantly paired to human residence times. The proposed method demonstrated that the residence time of 225Ac and its progeny was very similar within the same organ. The highest residence time of 225Ac-NOTA-trastuzuamb was observed in liver, measuring 2.57 × 10− 2 MBq·h/MBq, while stomach exhibited the lowest residence time of 8.24 × 10− 4 MBq·h/MBq. The estimated effective dose of 225Ac-NOTA-trastuzumab was 6.64 × 10− 1 mSv/MBq. CONCLUSIONS: In this study, we estimated human equivalent dose of 225Ac-NOTA-trastuzumab using preclinical data of 64Cu-NOTA-trastuzumab. Extrapolation method based on biological half-life allometry produced results consistent with clinical data. To account for dose contribution from daughter radionuclides, extrapolation method was corrected with the solution of Bateman equation. Our proposed method is capable of calculating the radiopharmaceutical’s residence time in human from preclinical distribution data while considering the contribution of daughter radionuclide.