Estimation of human absorbed radiation dose of radiopharmaceuticals based on animal biodistribution data: A review from last decade

A radiopharmaceutical is a drug that contains radiation that can harm humans if the risk is not identified. To ensure that novel radiopharmaceuticals have safe pharmacology, radiation effects, and toxicity properties, a preclinical trial should be performed, which animals were imaged or sacrificed with the aim of extrapolating into the human absorbed radiation dose. To the best of the author's knowledge, there is no review regarding human absorbed radiation dose estimation for new radiopharmaceuticals available in the literature. Due to the importance of how human dose estimation should be conducted, and since there are no gold standards in human absorbed radiation dose translation from animal data, this article provides a summary of the contributed factors in which were utilized by numerous studies over the past decade. Literature searches in PubMed (https://pubmed.ncbi.nlm.nih.gov/) with keywords: preclinical biodistribution, human absorbed radiation dose, radiation calculation, absorbed dose, and pharmacokinetics, was conducted for relevant studies published between 2013 and 2023. Initially, 120 articles were selected. After the exclusion due to lack of preclinical data and unclear dosimetry data, fifty-three articles were chosen for this study. As a result, about 40.8% of radiopharmaceuticals were fitted using a mono-exponential method or a combination of mono-exponential and bi-exponential methods (14.1%), a bi-exponential method alone (9.9%), or a multiexponential method (11.3%), the rest of the studies (22.5%) were not mentioned how the time-integrated activity coefficients (TIAC) were produced. Compared with animal and human data, extrapolation strategies ranged from direct (16.9%) to scaling (78.9%), with 2.8% of radiopharmaceuticals lacking a translation method. Most studies (75.7%) used OLINDA/EXM dosimetry software. The remaining studies (24.3%) use MIRDOSE/MIRD, IDAC, or MCNPX to calculate the effective dose in mSv/MBq or mGy. According to ICRP Publication 62, Radiological Protection in Biomedical Research, the majority of these novel radiopharmaceuticals are categorized as having moderate radiation risk (76.1%), low radiation risk (12.7%), or very low radiation risk (11.3%). This study concludes that MIRD methodologies with an additional tool, such as OLIINDA EXM, were primarily used to calculate the effective dose. Therefore, the extrapolation procedure from animal biodistribution data to humans was suggested to be standardized.