Dosimetry, Radiobiology and Synthetic Lethality: Radiopharmaceutical Therapy (RPT) With Alpha-Particle-Emitters.

As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha-particles cause a preponderance of complex DNA double-strand breaks (DSBs). This provides an opportunity to either enhance cell kill by using DNA DSB repair inhibitors or identify patients who are likely to be high responders to alpha-emitter RPT. The short-range and high potency of alpha-particles requires special dosimetry considerations. These are reviewed in light of recent updates to the phantoms and associated dosimetric quantities used for dosimetry calculations. A formalism for obtaining the necessary microscale pharmacokinetic information from patient nuclear medicine imaging is presented. Alpha-emitter based radiopharmaceutical therapy is an exciting cancer therapy modality that is being revisited. Further development of imaging and dosimetric methods specific to alpha-particle emitters, coupled with standardization of the methods and rigorous evidence that dosimetry applied to alphaRPT improves patient care are needed moving forward.