Bridging the resolution gap in alpha therapy dosimetry: a space for quantitative MRI?

While external beam radiotherapy relies heavily on pre-treatment imaging for advanced treatment planning and radiation dosimetry, tools for predicting local dose delivery in systemic radiopharmaceutical therapies have generally lagged behind. Furthermore, targeted alpha particle-emitting radiopharmaceuticals, with their uniquely short range and high-energy dose deposition, require specialized dosimetry methods at the micro- and mesoscale. Magnetic resonance imaging methods may represent the missing link between standard diagnostic tumor imaging and personalized radionuclide treatment planning for patients. For example, dynamic susceptibility contrast magnetic resonance imaging reveals markedly heterogeneous tumor perfusion patterns and vascular permeability from patient to patient, suggesting variable local drug delivery, but this information is only used in rudimentary ways or not at all in treatment planning. Similarly, emerging diffusion magnetic resonance imaging (MRI) methods may provide information relevant to microscale dosimetry, such as local cell size and density. In this review, we explore advancements in MRI and computational modeling strategies that could improve our fundamental understanding of radionuclide transport in solid tumors and enable pre-treatment, patient-specific predictions of dose delivery at a biologically relevant length scale.