We study targeted liposomes loaded with the alpha-particle generator Actinium-225 (225Ac) to selectively kill prostate-specific-membrane-antigen-(PSMA)-expressing cells with the aim to evaluate their potential for targeted antivascular alpha-radiotherapy. This is a bottom-up design and the rationale for the chosen components is the following: The targeted moiety is PSMA which is unique to human tumor vasculature for several different types of primary human cancers. The therapeutic radionuclide, 225Ac, emits a total of four alpha-particles per decay providing highly lethal and localized irradiation of targeted cells with minimal exposure of surrounding healthy tissues. And, finally, the delivery carrier is a lipid-based nanocarrier (a liposome). Liposomes can be loaded with high radioactivities, and, in terms of toxicities, liposomes can be easily engineered (by altering their size and surface characteristics) to become rapidly cleared from circulation with the aim to shift the distribution of normal organ toxicities away from the kidneys (the dose limiting organ in the case of 225Ac-labeled antibodies) and toward the spleen and the liver.
BANDEKAR Amey;
ZHU Charles;
JINDAL Rohit;
BANERJEE Sangeeta Ray;
POMPER Martin;
BRUCHERTSEIFER Frank;
MORGENSTERN Alfred;
SOFOU Stavroula;
2013-06-27
Oak Ridge National Laboratory
JRC82796
https://register.ornl.gov/2013/TATS/index.shtml,
https://publications.jrc.ec.europa.eu/repository/handle/JRC82796,
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