The unhindered transmission of malignant cells throughout the human body has been of peak interest within medical practices. There are multiple routes in which these cancerous cells may be targeted, such as surgical removal, direct irradiation, and chemotherapy. Radiopharmaceutical therapies act to bridge two of these practices by combining the effectiveness of irradiation therapies with the noninvasive nature of chemotherapy. To date, there has only been one α-particle emitting radiotherapy(223RaCl2) approved by the U.S. Food and Drug Association (FDA). Other α-emitting isotopes, such as 212Bi (t1/2= 60.6 m) and 211At (t1/2= 7.2 h), have been investigated, but lack a sufficiently long half-life to be effectively implemented into medical practice; however, the longer half-life of 223Ra (t1/2= 11.43 d) makes the isotope a more viable option for the future of radiotherapeutic therapies. Because of the high linear energy transfer inherent to α-particles, 223Ra treatments must be selective of which cells to target. Radium has a natural affinity for bones and tends to accumulate in cells associated with rapid bond remodeling (i.e. osteoclasts and osteoblasts). To make radium treatments selective for other types of cancerous cells, an effective chelator must be developed. A chelator must bind effectively to 223Ra in low concentrations and be tunable to allow for antibodies or other cell selective moieties to be linked. Thus far, only one type of chelator meets these requirements: macropa derivatives (6-((16-((6-Carboxypyridin-2-yl)methyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecan-7-yl)methyl)-4-isothiocyanatopicolinic acid). This research aims to determine the preferred coordination and bonding environment of radium to guide the development of an effective chelator for radium.

Chelating radium: Understanding the coordination and bonding environment of radium

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ACS Spring 2023

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