Abstract
Lead-212 is recognized as a promising radionuclide for targeted alpha therapy for tumors. Many studies of 212Pb-labeling of various biomolecules through bifunctional chelators have been conducted. Another approach to exploiting the cytotoxic effect is coupling the radionuclide to a microparticle acting as a carrier vehicle, which could be used for treating disseminated cancers in body cavities. Calcium carbonate may represent a suitable material, as it is biocompatible, biodegradable, and easy to synthesize. In this work, we explored 212Pb-labeling of various CaCO3 microparticles and developed a protocol that can be straightforwardly implemented by clinicians. Vaterite microparticles stabilized by pamidronate were effective as 212Pb carriers; labeling yields of ≥98% were achieved, and 212Pb was strongly retained by the particles in an in vitro stability assessment. Moreover, the amounts of 212Pb reaching the kidneys, liver, spleen, and skeleton of mice following intraperitoneal (i.p.) administration were very low compared to i.p. injection of unbound 212Pb2+, indicating that CaCO3-bound 212Pb exhibited stability when administered intraperitoneally. Therapeutic efficacy was observed in a model of i.p. ovarian cancer for all the tested doses, ranging from 63 to 430 kBq per mouse. Lead-212-labeled CaCO3 microparticles represent a promising candidate for treating intracavitary cancers.
Highlights
The use of alpha-emitting radionuclides in cancer research and drug development is increasing [1]. This is due to their radiation characteristics, including high energy, short range, and high linear energy transfer with associated irreversible DNA damage, which make alpha particles superior to beta particles in the treatment of disseminated single cancer cells and micrometastases
One alpha particle is emitted per complete decay of 212Pb on average, which accounts for approximately 77% of the total energy released during decay
Calcium carbonate is metastable in an aqueous solution due to continuous dissolution and re-precipitation
Summary
The use of alpha-emitting radionuclides in cancer research and drug development is increasing [1]. This is due to their radiation characteristics, including high energy, short range, and high linear energy transfer with associated irreversible DNA damage, which make alpha particles superior to beta particles in the treatment of disseminated single cancer cells and micrometastases. Several alpha-emitters have been evaluated for therapeutic use in clinical trials: 211At, 225Ac, (223, 224)Ra, 227Th, and 213Bi [1,2,3]. Lead-212, a beta emitter by itself, has attracted attention as an in vivo generator of alpha particles. One alpha particle is emitted per complete decay of 212Pb on average, which accounts for approximately 77% of the total energy released during decay
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