TY - JOUR
T1 - Alpha Particle–Emitting Radiopharmaceuticals as Cancer Therapy
T2 - Biological Basis, Current Status, and Future Outlook for Therapeutics Discovery
AU - Coll, Ryan P.
AU - Bright, Scott J.
AU - Martinus, David K.J.
AU - Georgiou, Dimitra K.
AU - Sawakuchi, Gabriel O.
AU - Manning, H. Charles
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to World Molecular Imaging Society.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Alpha emitter
KW - Cancer
KW - Radiochemistry
KW - Theranostics
UR - http://www.scopus.com/inward/record.url?scp=85174312638&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85174312638&partnerID=8YFLogxK
U2 - 10.1007/s11307-023-01857-y
DO - 10.1007/s11307-023-01857-y
M3 - Review article
C2 - 37845582
AN - SCOPUS:85174312638
SN - 1536-1632
VL - 25
SP - 991
EP - 1019
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 6
ER -