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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

203/212Pb Theranostic Radiopharmaceuticals for Image-guided Radionuclide Therapy for Cancer

Author(s): Mengshi Li, Edwin A. Sagastume, Dongyoul Lee, Daniel McAlister, Anthony J. DeGraffenreid, Keith R. Olewine, Stephen Graves, Roy Copping, Saed Mirzadeh, Brian E. Zimmerman, Roy H. Larsen, Frances L. Johnson and Michael K. Schultz*

Volume 27, Issue 41, 2020

Page: [7003 - 7031] Pages: 29

DOI: 10.2174/0929867327999200727190423

Price: $65

Abstract

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 considerable 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 improved-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 alpha emitters 212Bi and 212Po) is a particularly promising radionuclide for receptor-targeted alpha-particle therapy. A second attractive feature that distinguishes 212Pb alpha-TRT from other available radionuclides is the possibility to employ elementallymatched isotope 203Pb as an imaging surrogate in place of the therapeutic radionuclide. As direct non-invasive measurement 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 advance 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 methodologies applied for production and purification of these isotopes for radiopharmaceutical production. In addition, a medical physics and dosimetry perspective is provided that highlights the potential of 212Pb for alpha-TRT and the expected safety for 203Pb surrogate imaging. Recent and current preclinical and clinical studies are presented. The sum of the findings herein and observations presented provide evidence that the 203Pb/212Pb theranostic pair has a promising future for use in radiopharmaceutical theranostic therapies for cancer.

Keywords: Radiopharmaceuticals, radiochemistry, theranostics, Lead-212, Lead-203, Pb-203, Pb-212, dosimetry, cancer, radionuclide therapy, SPECT imaging, MIRD, voxel-based dosimetry.

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