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-produced212Pb (which decays to alpha emitters212Bi and212Po) is a particularly promising radionuclide for receptor-targeted alpha-particle therapy. A second attractive feature that distinguishes212Pb alpha-TRT from other available radionuclides is the possibility to employ elementallymatched isotope203Pb 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-matched203Pb labeled radiopharmaceuticals can be used to identify patients who may benefit from212Pb 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 of203/212Pb 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 of212Pb for alpha-TRT and the expected safety for203Pb surrogate imaging. Recent and current preclinical and clinical studies are presented. The sum of the findings herein and observations presented provide evidence that the203Pb/212Pb theranostic pair has a promising future for use in radiopharmaceutical theranostic therapies for cancer.
| Original language | English |
|---|---|
| Pages (from-to) | 7003-7031 |
| Number of pages | 29 |
| Journal | Current Medicinal Chemistry |
| Volume | 27 |
| Issue number | 41 |
| DOIs | |
| State | Published - 2020 |
Funding
This work has been partially supported by the following grants from the US National Institutes of Health (MKS, ML): 1R01CA243014, 1P50CA174521, and P30 CA86862. This work has been partially supported by the following grants from the US National Institutes of Health (MKS, ML): 1R01CA243014, 1P50CA174521, and P30 CA86862.The authors thank and acknowledge the following University of Iowa organizations: The Department of Radiology and Division of Nuclear Medicine; the Free Radical and Radiation Biology Program, the Holden Comprehensive Cancer Center, and the College of Medicine. Work at ORNL was supported by the U.S. Department of Energy Isotope Program, managed by the Office of Science for Isotope R&D and Production. ORNL is managed by UT-Battelle, LLC, under contract DE-AC05-00OR22725 with the US Department of Energy. Work at ORNL was supported by the U.S. Department of Energy Isotope Program, managed by the Office of Science for Isotope R&D and Production. ORNL is managed by UT-Battelle, LLC, under contract DE-AC05-00OR22725 with the US Department of Energy.
Keywords
- Cancer
- Dosimetry
- Lead-203
- Lead-212
- MIRD
- Pb-203
- Pb-212
- Radiochemistry
- Radionuclide therapy
- Radiopharmaceuticals
- SPECT imaging
- Theranostics
- Voxel-based dosimetry