Dosimetry, Radiobiology and Synthetic Lethality: Radiopharmaceutical Therapy (RPT) With Alpha-Particle-Emitters
Open accessAbstract
As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha-particles cause a preponderance of complex DNA double-strand breaks (DSBs). This provides an opportunity to either enhance cell kill by using DNA DSB repair inhibitors or identify patients who are likely to be high responders to alpha-emitter RPT. The short-range and high potency of alpha-particles requires special dosimetry considerations. These are reviewed in light of recent updates to the phantoms and associated dosimetric quantities used for dosimetry calculations. A formalism for obtaining the necessary microscale pharmacokinetic information from patient nuclear medicine imaging is presented. Alpha-emitter based radiopharmaceutical therapy is an exciting cancer therapy modality that is being revisited. Further development of imaging and dosimetric methods specific to alpha-particle emitters, coupled with standardization of the methods and rigorous evidence that dosimetry applied to alphaRPT improves patient care are needed moving forward.
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Most forms of radiation exert DNA effects primarily through intermediary oxygen free radicals, while alpha-particles are more likely to interact directly with DNA.
“Although most forms of radiation exert DNA effects primarily through intermediary oxygen free radicals, a -particles are more likely to interact directly with the DNA ( 23 ).”
From Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns (2021) · cites this paper as [23]
The Introduction and Radiobiology and Synthetic Lethality sections (page unavailable) describe alpha-particles depositing DNA-damaging energy much more densely than photons or beta-particles and causing DNA double-strand breaks. They do not say that alpha-particles are more likely to interact directly with DNA, or that most other radiation damages DNA primarily through oxygen free radicals. (LLM, conf=0.79)
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- [13]Ghaly M, Sgouros G, and Frey E, Quantitative Dual Isotope SPECT Imaging of the alpha-emitters Th-227 and Ra-223. Journal of Nuclear Medicine, 2019 60(supplement 1): p. 41– 41.30030338
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Normal-Tissue Tolerance to Radiopharmaceutical Therapies, the Knowns and the Unknowns
Wahl, R. L., Sgouros, G., Iravani, A., Jacene, H., Pryma, D., Saboury, B., Capala, J., & Graves, S. A. (2021) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.262751 · Cited by 95 · see citing works
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- Authors
- Sgouros, G.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Sgouros, George
- ORCID
- Sgouros, George
- Venue
- Seminars in Nuclear Medicine
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 50
- Issue
- 2
- Pages
- 124-132
- ISSN
- 0001-2998 (ISSN-L)
- PMC
- PMC7204891
- OpenAlex
- W3008344257
- Cited by
- 60
- References
- 29
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 11 · 2023: 5 · 2022: 7 · 2021: 12 · 2020: 2 · 2018: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
- Keywords
- radiopharmaceutical therapy, alpha-emitting radionuclides, dosimetry, radiation biology, synthetic lethality, DNA double-strand breaks, DNA repair inhibitors, patient-specific dosimetry, dosimetric phantoms, scintigraphy
- MeSH terms
- Alpha Particles, Humans, Radiobiology, Radiometry, Radiopharmaceuticals
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