An analytic dosimetry study for the use of radionuclide-liposome conjugates in internal radiotherapy.

Abstract

A dosimetric analysis has been performed to evaluate the potential of liposome systems as carriers of radionuclides in internal radiotherapy. Pharmacokinetic data for a variety of liposome constructs (multilamellar vesicles [MLV]; small unilamellar vesicles [SUV]; and sterically stabilized liposomes, monosialoganglioside [G(M1)]-coated) were used to obtain tumor and normal-organ absorbed dose estimates for (67)Cu, (188)Re, (90)Y, and (131)I. Dosimetry was performed for two tumor models: subcutaneous Ehrlich ascites tumor, growing intramuscularly, and C26 colon carcinoma, growing intrahepatically. Dose estimates were obtained using the MIRD schema. Tumor doses were obtained assuming local deposition of electron energy; photon contributions were incorporated assuming spheric tumor geometry. With the conservative assumption that intravenously administered liposomes achieve rapid equilibration with the red marrow extracellular fluid volume, red marrow absorbed dose estimates were obtained from blood kinetics. For intramuscular tumors, absorbed dose ratios for tumor to red marrow ranged from 0.93 ((131)I-MLV) to 13.9 ((90)Y-SUV). Tumor-to-liver ratios ranged from 0.08 ((188)Re-MLV) to 0.92 ((188)Re-SUV); corresponding values for tumor to spleen were 0.13 ((90)Y-MLV) and 0.54 ((188)Re-G(M1)). The optimal combination of radionuclide and liposome system was obtained with (90)Y-SUV. Tumor-to-liver ratios for the G(M1)-coated construct were greatest when the tumor was intrahepatic (1.13 for (90)Y). For a given liposome system, absorbed dose ratios for tumor to normal tissue exhibited up to a twofold variation depending on the radionuclide selected. This study provides a dosimetric evaluation for the use of some liposome systems as carriers in targeted radionuclide therapy. Although much further work must be undertaken before any clinical application is considered, these results suggest that radionuclide targeting using liposomes is feasible and may have the advantage of reduced red marrow absorbed dose.