203/212Pb theranostic radiopharmaceuticals for image-guided radionuclide therapy for cancer.

Receptor-targeted image-guided radionuclide therapy (TRT) is increasingly recognized as a promising approach to cancer treatment. In particular, the potential for clinical translation of receptor-targeted alpha-particle therapy is receiving con- siderable attention as an approach that can improve outcomes for cancer patients. Higher linear-energy transfer (LET) of alpha- particles (compared to beta particles) for this purpose results in an increased incidence of double-strand DNA breaks and im- proved-localized cancer-cell damage. Recent clinical studies provide compelling evidence that alpha-TRT has the potential to deliver a significantly more potent anti-cancer effect compared with beta-TRT. Generator-produced 212Pb (which decays to al- pha emitters 212Bi and 212Po) is a particularly promising radionuclide for receptor-targeted alpha-particle therapy. A second at- tractive feature that distinguishes 212Pb alpha-TRT from other available radionuclides is the possibility to employ elementally- matched isotope 203Pb as an imaging surrogate in place of the therapeutic radionuclide. Because direct non-invasive measure- ment of alpha-particle emissions cannot be conducted using current medical scanner technology, the imaging surrogate allows for a pharmacologically-inactive determination of the pharmacokinetics and biodistribution of TRT candidate ligands in ad- vance of treatment. Thus, elementally-matched 203Pb labeled radiopharmaceuticals can be used to identify patients who may benefit from 212Pb alpha-TRT and apply appropriate dosimetry and treatment planning in advance of the therapy. In this review, we provide a brief history on the use of these isotopes for cancer therapy; describe the decay and chemical characteristics of 203/212Pb for their use in cancer theranostics and methologies applied for production and purification of therapies for cancer.