Radionuclide therapy with iodine-125 and other Auger-electron-emitting radionuclides: Experimental models and clinical applications

Auger-electron emitters represent an attractive alternative to beta-particle emitters for cancer therapy if they can be placed intracellularly, especially in close proximity to (or within) nuclear DNA. Based on investigations in animal tumor models, including those for ovarian cancer, bladder cancer, and brain and spinal cord tumors, in which the thymidine analog 5-radioiodo-2'-deoxyuridine (*IUdR) has been shown to be therapeutically efficacious, it is hypothesized that iodine-125 and other Auger-electron-emitting radionuclides might be valuable in the treatment of certain malignant diseases, assuming that uptake of the radiopharmaceutical by tumor cells exceeds that by normal dividing cells. Preliminary patient studies have shown that this requirement can be met partially by the locoregional administration of the radiopharmaceutical and metabolic modulation of its uptake by tumor cells. Investigators continue to seek molecules that can carry Auger-electron emitters to nuclear DNA, especially those radionuclides with higher Auger-electron yields and varying half-lives.