Towards Routine Clinical Use of Dosimetry in [177Lu]Lu-PSMA Prostate Cancer Radionuclide Therapy: Current Efforts and Future Perspectives

In light of widely expanding personalized medicine applications and their impact on clinical outcomes, it is naturally befitting to explore all the dimensional aspects of personalized radionuclide therapy (RNT). Adoption of absorbed radiation dose into clinical practice in the field of RNT has been hampered by difficulties such as evidence of dose-effect correlation, technical requirements in quantitative imaging of the radiopharmaceutical, heterogeneity of methods between not only centers, but also across software, hardware and radionuclides used. Additionally, standardized agreed upon definition of outcome measures is being debated whether it be solely related to toxicity, quality of life, survival or other measures. Many clinical RNT activity administrations are still based on empirical/fixed activities, or scaled based on parameters such as body surface area. Although still challenging, a tremendous amount of progress has been made to facilitate routine clinical dosimetry with discussions regarding standardization, harmonization and automated processing techniques. This has also been aided by the development and FDA approval of several companion diagnostics allowing within the theranostic paradigm not only a crude qualitative predictive biomarker but also an objective dosimetry based predictive therapeutic biomarker. This work aims to review the literature of [ 177 Lu]Lu-PSMA RNT, focusing on clinical trials and studies, with the goal to summarize the range of dosimetry techniques and the range of doses calculated to organs and tissues of interest from these techniques. A dosimetry method for [ 177 Lu]Lu-PSMA RNT should be reliable, reproducible and encompassing the knowledge gained from all clinical trials evaluating it. Its translation into clinical routine practice can be achieved with the confirmation that dose calculation represents good clinical efficacy and low treatment-related toxicity. Finally, some future perspectives on the future of [ 177 Lu]Lu-PSMA RNT are made, especially in the rapidly emerging field of artificial intelligence (AI), where deep learning may be able to play a large role in the simplification of dosimetry calculations to aid in their clinical adoption.