Liposome-Mediated Delivery of Radionuclides to Tumor Models for Cancer Radiotherapy: A Quantitative Analysis

Abstract

Towards the design of therapeutically effective liposome-radionuclide conjugates, the predominant focus should rest with the ability of such modalities to efficiently target tumor sites and thus selectively deliver cytotoxic levels of radiation doses. For this reason analytic dosimetric calculations were carried out to quantitatively examine the critical physical parameters for the potential clinical application of radionuclide-liposome conjugates in internal radiotherapy. The radiodosimetric model employed followed the mathematical formalism of the MIRD (Medical Internal Radiation Dose Committee) scheme. Analytic pharmacokinetic functions for a variety of liposome constructs coupled with the radiation properties of three of the most promising particle emitting radionuclides: Cu-67, Re-188, At-211 and the most widely used in the clinic 1-131, were used as input information to the model developed. Results are presented in the form of radiation absorbed doses and tumor-to-normal-tissue radiation ratios. It is concluded that liposome-mediated radionuclide tumor targeting for radiotherapy is certainly promising, and critically dependent on the optimal matching between radionuclide half-life and the time range when the tumor-to-(critical)organ liposome accumulation ratios become maximal. Liposome-mediated chemotherapy (drug targeting) is also comparatively discussed demonstrating the predominant importance of “timing factors” in the case of radiotherapeutic (radionuclide targeting) applications.