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

A dosimetric analysis has been performed to evaluate the potential of lipos ome systems as carriers of radionuclides in internal radiotherapy. Methods: Pharmacokinetic data for a Variety of liposome constructs (multilamellar v esicles [MLV]; small unilamellar vesicles [SUV]; and sterically stabilized liposomes, monosialoganglioside [G(M1)]-coated) were used to obtain tumor a nd normal-organ absorbed dose estimates for Cu-67,Re-188, Y-90, and I-131. Dosimetry was performed for two tumor models: subcutaneous Ehrlich ascites tumor, growing intramuscularly, and C26 colon carcinoma, growing intrahepat ically. Dose estimates were obtained using the MIRD schema. Tumor doses wer e obtained assuming local deposition of electron energy; photon contributio ns were incorporated assuming spheric tumor geometry. With the conservative assumption that intravenously administered liposomes achieve rapid equilib ration with the red marrow extracellular fluid volume, red marrow absorbed dose estimates were obtained from blood kinetics. Results: For intramuscula r tumors, absorbed dose ratios for tumor to red marrow ranged from 0.93 (I- 131-MLV) to 13.9 (Y-90-SUV). Tumor-to-liver ratios ranged from 0.08 (Re-188 -MLV) to 0.92 (Re-188-SUV); corresponding Values for tumor to spleen were 0 .13 (Y-90-MLV) and 0.54 (Re-188-G(M1)). The optimal combination of radionuc lide and liposome system was obtained with Y-90-SUV. Tumor-to-liver ratios for the G(M1)-coated construct were greatest when the tumor was intrahepati c (1.13 for Y-90). For a given liposome system, absorbed dose ratios for tu mor to normal tissue exhibited up to a twofold variation depending on the r adionuclide selected. Conclusion: This study provides a dosimetric evaluati on for the use of some liposome systems as carriers in targeted radionuclid e therapy. Although much further work must be undertaken before any clinica l application is considered, these results suggest that radionuclide target ing using liposomes is feasible and may have the advantage of reduced red m arrow absorbed dose.