Theranostic digital twins: Concept, framework and roadmap towards personalized radiopharmaceutical therapies.

Radiopharmaceutical therapy (RPT) is a rapidly developing field of nuclear medicine, with several RPTs already well established in the treatment of several different types of cancers. However, the current approaches to RPTs often follow a somewhat inflexible "one size fits all" paradigm, where patients are administered the same amount of radioactivity per cycle regardless of their individual characteristics and features. This approach fails to consider inter-patient variations in radiopharmacokinetics, radiation biology, and immunological factors, which can significantly impact treatment outcomes. To address this limitation, we propose the development of theranostic digital twins (TDTs) to personalize RPTs based on actual patient data. Our proposed roadmap outlines the steps needed to create and refine TDTs that can optimize radiation dose to tumors while minimizing toxicity to organs at risk. The TDT models incorporate physiologically-based radiopharmacokinetic (PBRPK) models, which are additionally linked to a radiobiological optimizer and an immunological modulator, taking into account factors that influence RPT response. By using TDT models, we envisage the ability to perform virtual clinical trials, selecting therapies towards improved treatment outcomes while minimizing risks associated with secondary effects. This framework could empower practitioners to ultimately develop tailored RPT solutions for subgroups and individual patients, thus improving the precision, accuracy, and efficacy of treatments while minimizing risks to patients. By incorporating TDT models into RPTs, we can pave the way for a new era of precision medicine in cancer treatment