Abstract
Radioisotopes that emit electrons (beta particles), such as radioiodine, can effectively kill target cells, including cancer cells. Aqueous 32P[PO4] is a pure beta-emitter that has been used for several decades to treat non-malignant human myeloproliferative diseases. 32P[PO4] was directly compared to a more powerful pure beta-emitter, the clinically important 90Y isotope. In vitro, 32P[PO4] was more effective at killing cells than was the more powerful isotope 90Y (P ≤ 0.001) and also caused substantially more double-stranded DNA breaks than did 90Y. In vivo, a single low-dose intravenous dose of aqueous elemental 32P significantly inhibited tumor growth in the syngeneic murine cancer model (P ≤ 0.001). This effect is exerted by direct incorporation into nascent DNA chains, resulting in double-stranded breakage, a unique mechanism not duplicatable by other, more powerful electron-emitting radioisotopes. 32P[PO4] should be considered for human clinical trials as a potential novel anti-cancer drug.
Highlights
Beta particles emitted by radioisotopes are known to efficiently kill cancer cells
Beta particle-emitting radiolabeled antibodies directed against CD20, including 131I-Bexxar and 90Y-Zevalin, have been used against non-Hodgkin’s lymphoma [2,3]
The resulting bystander effect amplifies the lethal potential of each beta particle emitted in or near a tumor
Summary
Beta particles (electrons) emitted by radioisotopes are known to efficiently kill cancer cells. This finding has already been clinically exploited by using 131I to treat thyroid cancer [1], a strategy still employed successfully in more than 50% of such patients in the United States, with over a 90% cure rate. 90Y-labeled somatostatin receptor ligand is utilized to treat neuroendocrine tumors [4]. Electrons emitted by 32P have an energy level intermediate between those of 131I and the more powerful 90Y, resulting in a path length of up to 5 mm in human tissues [5]. Electrons emitted from radioisotopes can strike thousands of cells. The resulting bystander effect amplifies the lethal potential of each beta particle emitted in or near a tumor.
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