Introduction: Alpha particle-emitting radioisotopes of radium (Ra), actinium (Ac), and other heavy elements have garnered tremendous interest for their potential use in cancer therapy. Of the alpha emitters currently under investigation, only Ra (t1/2 = 11.43 d) is approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). It is administered as unchelated RaCl2 in the drug XOFIGO® and is used to treat patients with castration-resistant prostate cancer that has metastasized to the bone. Because of the chemical similarity it shares with the calcium ion (Ca 2+ ), Ra 2+ naturally accumulates in areas of increased bone turnover associated with metastases, where its alpha-particle emissions irradiate and destroy cancer cells. Despite the success of Ra for this indication, its more widespread application for the treatment of visceral cancers has remained hindered because of the difficulty in stabilizing this radiometal within a tumor-targeted molecular construct. The lability of Ra 2+ complexes arises because Ra 2+ forms ionic, rather than covalent, bonds with ligands, which are weakened by the low charge density of this large alkaline earth ion (8-coordinate ionic radius = 1.48 Å). As such, a chelator that can deliver Ra to soft-tissue tumors remains elusive.