On the Use of 203Pb Imaging to Inform 212Pb Dosimetry for 203/212Pb Image-Guided Alpha-Particle Therapy for Cancer

AbstractAlpha-emitting radiopharmaceutical therapy shows promise for improving the therapeutic efficacy of existing and future targeting ligands by limiting off-target irradiation and by preempting many cell survival mechanisms. Dosimetry-guided therapies are emerging as potentially safer and more effective than approaches based on a fixed-activity-administration paradigm. Among the candidates of alpha-emitting radionuclides, 212Pb shows promise for use under an image-guided dosimetry-informed theranostic paradigm, whereby 203Pb can be used for dosimetry and treatment planning. In this chapter, we model an approach to accurately estimate the dosimetry of 212Pb-based radiopharmaceuticals using 203Pb as a surrogate. However, uncertainties arise in dosimetric predictions for 212Pb based on 203Pb imaging due to the potential for migration of 212Pb radionuclide progeny (i.e., 212Bi, 212Po, 208Tl) from the site of 212Pb decay. On the other hand, based on distinct gamma-ray energies of the 212Pb progeny, the design of in vivo experiments is described that have the potential to define these uncertainties more precisely, so as to gain insights into the potential toxicity of bioconjugated and potentially decoupled 212Bi in tissues. The promise of alpha-particle radionuclide therapy is evidenced by a tenfold increase in publications over the last 30 years, and it is anticipated that the elementally matched 203Pb/212Pb radionuclide pair will play a key role in our progress toward personalized receptor-targeted alpha-particle therapy for cancer.