Radium and other alpha emitters in prostate cancer
223Radium (223Ra) is the first alpha-emitting therapy proven effective in human cancer. Prospective randomized trials indicate that 223Ra, which concentrates after intravenous injection in areas of osteoblastic metastatic disease, can prolong survival in bone-dominant castrate resistant prostate cancer patients. Though radium isotopic therapy is conceptually critical to demonstrate that alpha emitters can be safe and effective, 223Ra has inherent limitations given its restriction to bone metastatic disease. To overcome this limitation, targeted alpha therapy (TAT) is now being actively evaluated in prostate cancer, and other neoplasms. Key to TAT in prostate tumors in current studies is the overexpression of prostate specific membrane antigen (PSMA), a folate hydrolase expressed on the cell surface of malignant adenocarcinomas of the prostate. Using PSMA targeting (small molecules or antibodies), alpha emitting agents such as 225Actinium (225Ac) or 213Bismuth (213Bi) can be delivered to PSMA expressing tumors regardless of their metastatic location. Initial results from TAT in prostate cancer are highly promising and rapid development of these agents is anticipated in the years ahead assuming adequacy of isotope availability and appropriate clinical trial design. TAT may be develop as an independent approach, or synergize with a variety of other approaches including external beam radiation, hormonal therapies, chemotherapies, various radiation sensitizers, DNA repair inhibitors, and/or immune modulators. Clinical investigation opportunities in this field will rapidly increase in the years ahead.