Alpha-particles for targeted therapy.
Alpha-particles are helium nuclei that deposit DNA damaging energy along their track that is 100 to 1000 times greater than that of conventionally used beta-particle emitting radionuclides for targeted therapy; the damage caused by alpha-particles is predominately double-stranded DNA breaks severe enough so as to be almost completely irreparable. This means that a small number of tracks through a cell nucleus can sterilize a cell and that, because the damage is largely irreparable, alpha-particle radiation is not susceptible to resistance as seen with external radiotherapy (e.g., in hypoxic tissue). The ability of a single track to influence biological outcome and the stochastic nature of alpha-particle decay require statistical or microdosimetric techniques to properly reflect likely biological outcome when the biologically relevant target is small or when a low number of radionuclide decays have occurred. In therapeutic implementations, microdosimetry is typically not required and the average absorbed dose over a target volume is typically calculated. Animal and cell culture studies have shown that, per unit absorbed dose, the acute biological effects of alpha-particles are 3 to 7 times greater than the damage caused by external beam or beta-particle radiation. Over the past ten to 15 years, alpha-particle emitting radionuclides have been investigated as a possible new class of radionuclides for targeted therapy. Results from the small number of clinical trials reported to date have shown efficacy without significant toxicity.
Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, School of Medicine, Baltimore MD USA. gsgouro1@jhmi.edu
George
G
Sgouros
D000512:Alpha Particles / Q000627:therapeutic use; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness