Tissue dosimetry of liposome-radionuclide complexes for internal radiotherapy: Toward liposome-targeted therapeutic radiopharmaceuticals

Background: Quantitative examination of the important physical parameters, such as the tumor absorbed dose and the tumor-to-normal-tissue (T-NT) absor bed dose ratios, for effective use of radionuclide-liposome conjugates m in ternal radiotherapy was carried out. Methods: The Medical Internal Radiatio n Dose (MIRD) formalism was used to develop a set of dosimetric equations. Pharmacokinetic functions used as input information to the dosimetric model were derived from experimental time-biodistribution data. Multilamellar (M LV), small unilamellar (SW) and sterically stabilized (GM1- and PEG- coated ) liposomes were examined in combination with the very promising pal-tide e mitting radionuclides: Cu-67, Re-188 and Ar-211. For comparative purposes, the widely used: Y-90 and I-131 were also included in the study. For all ra dionuclide-liposome combinations, the mean absorbed dose per amount of radi oactivity administered was obtained: (i) for two different types of human x enografts located in the muscle and liver tissue, and (ii) for normal liver , spleen, kidneys, and total body. Results: Regardless of radionuclide, the poorest values were obtained for the MLV liposomes. Due to more rapid upta ke of sterically stabilized (GM,-coated) liposomes to the muscle tumor tiss ue as compared to SUVs, At-211 and Re-188 deliver higher tumor doses when c ombined with the former, while Cu-67, Y-90 and I-131 are mole effective wit h SUVs. The most promising results were obtained for the [At-211-G(M1)] com plex in the liver tumor: Conclusion: The importance of liposome size and st eric barrier when designing effective radionuclide-carrier systems was reve aled, but most importantly the optimal matching between the radionuclide ha lf-life and the time of maximum liposome accumulation ratio between the tum or and normal tissue.