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Alpha Particle–Emitting Radiopharmaceuticals as Cancer Therapy: Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery
Ist Teil von
Molecular imaging and biology, 2023-12, Vol.25 (6), p.991-1019
Ort / Verlag
Cham: Springer International Publishing
Erscheinungsjahr
2023
Link zum Volltext
Quelle
SpringerLink (Online service)
Beschreibungen/Notizen
Critical advances in radionuclide therapy have led to encouraging new options for cancer treatment through the pairing of clinically useful radiation-emitting radionuclides and innovative pharmaceutical discovery. Of the various subatomic particles used in therapeutic radiopharmaceuticals, alpha (
α
) particles show great promise owing to their relatively large size, delivered energy, finite pathlength, and resulting ionization density. This review discusses the therapeutic benefits of
α
-emitting radiopharmaceuticals and their pairing with appropriate diagnostics, resulting in innovative “theranostic” platforms. Herein, the current landscape of
α
particle-emitting radionuclides is described with an emphasis on their use in theranostic development for cancer treatment. Commonly studied radionuclides are introduced and recent efforts towards their production for research and clinical use are described. The growing popularity of these radionuclides is explained through summarizing the biological effects of
α
radiation on cancer cells, which include DNA damage, activation of discrete cell death programs, and downstream immune responses. Examples of efficient
α
-theranostic design are described with an emphasis on strategies that lead to cellular internalization and the targeting of proteins involved in therapeutic resistance. Historical barriers to the clinical deployment of
α
-theranostic radiopharmaceuticals are also discussed. Recent progress towards addressing these challenges is presented along with examples of incorporating
α
-particle therapy in pharmaceutical platforms that can be easily converted into diagnostic counterparts.