Journal article
203/212Pb Theranostic Radiopharmaceuticals for Image-guided Radionuclide Therapy for Cancer
Current medicinal chemistry, Vol.27(41), pp.7003-7031
12/08/2020
DOI: 10.2174/0929867327999200727190423
PMCID: PMC10613023
PMID: 32720598
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.
Details
- Title: Subtitle
- 203/212Pb Theranostic Radiopharmaceuticals for Image-guided Radionuclide Therapy for Cancer
- Creators
- Mengshi Li - Department of Radiology, The University of Iowa, Iowa City, IA 52240, United StatesEdwin A Sagastume - Viewpoint Molecular Targeting, Inc., Coralville, Iowa 52241, United StatesDongyoul Lee - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52241, United StatesDaniel McAlister - Eichrom Technologies, LLC, Lisle, IL 60532, United StatesAnthony J DeGraffenreid - Lantheus Medical Imaging, North Billerica, MA 01862, United StatesKeith R Olewine - Lantheus Medical Imaging, North Billerica, MA 01862, United StatesStephen Graves - Department of Radiology, The University of Iowa, Iowa City, IA 52240, United StatesRoy Copping - Oak Ridge National Laboratory, Oak Ridge Tennessee 37831, United StatesSaed Mirzadeh - Oak Ridge National Laboratory, Oak Ridge Tennessee 37831, United StatesBrian E Zimmerman - The National Institute of Standards and Technology, Gaithersburg, MD 20899, United StatesRoy H Larsen - Sciencons, AS, Oslo, NorwayFrances L Johnson - Viewpoint Molecular Targeting, Inc., Coralville, Iowa 52241, United StatesMichael K Schultz - Viewpoint Molecular Targeting, Inc., Coralville, Iowa 52241, United States
- Resource Type
- Journal article
- Publication Details
- Current medicinal chemistry, Vol.27(41), pp.7003-7031
- DOI
- 10.2174/0929867327999200727190423
- PMID
- 32720598
- PMCID
- PMC10613023
- NLM abbreviation
- Curr Med Chem
- ISSN
- 0929-8673
- eISSN
- 1875-533X
- Grant note
- DOI: 10.13039/100000002, name: US National Institutes of Health, award: 1R01CA243014, 1P50CA174521, P30 CA86862
- Language
- English
- Date published
- 12/08/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Stead Family Department of Pediatrics; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984216569802771
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