Overlooked potential of positrons in cancer therapy

• Published in: Scientific reports Vol. 11; no. 1; p. 2475
• Main Authors: Hioki, Takanori, Gholami, Yaser H, McKelvey, Kelly J, Aslani, Alireza, Marquis, Harry, Eslick, Enid M, Willowson, Kathy P, Howell, Viive M, Bailey, Dale L
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 28.01.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Cancer; Cancer therapies; Cytotoxicity; Glycolysis; Metabolism; Monte Carlo simulation; Nuclear medicine; Positron emission tomography; Prostate cancer; Radioisotopes
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-81910-4

Positron (β ) emitting radionuclides have been used for positron emission tomography (PET) imaging in diagnostic medicine since its development in the 1950s. Development of a fluorinated glucose analog, fluorodeoxyglucose, labelled with a β emitter fluorine-18 ( F-FDG), made it possible to image cellular targets with high glycolytic metabolism. These targets include cancer cells based on increased aerobic metabolism due to the Warburg effect, and thus, F-FDG is a staple in nuclear medicine clinics globally. However, due to its attention in the diagnostic setting, the therapeutic potential of β emitters have been overlooked in cancer medicine. Here we show the first in vitro evidence of β emitter cytotoxicity on prostate cancer cell line LNCaP C4-2B when treated with 20 Gy of F. Monte Carlo simulation revealed thermalized positrons (sub-keV) traversing DNA can be lethal due to highly localized energy deposition during the thermalization and annihilation processes. The computed single and double strand breakages were ~ 55% and 117% respectively, when compared to electrons at 400 eV. Our in vitro and in silico data imply an unexplored therapeutic potential for β emitters. These results may also have implications for emerging cancer theranostic strategies, where β emitting radionuclides could be utilized as a therapeutic as well as a diagnostic agent once the challenges in radiation safety and protection after patient administration of a radioactive compound are overcome.