A dosimetric analysis was performed to evaluate nanoliposomes as carriers of radionuclides (Re-188-liposomes) and radiochemotherapeutic drugs [Re-188-doxorubicin (DXR)-liposomes] in internal radiotherapy for colon carcinoma, as evaluated in mice. Methods: Pharmacokinetic data for Re-188-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), Re-188-liposome, and Re-188-DXR-liposome were obtained for the estimation of absorbed doses in tumors and normal organs. Two colon carcinoma mouse models were employed: subcutaneous growing solid tumor and malignant ascites pervading tumor models. Radiation-dose estimates for normal tissues and tumors were calculated by using the OLINDA/EXM program. An evaluation of a recommended maximum administered activity (MAA) for the nanotargeted drugs was also made. Results: Mean absorbed closes derived from Re-188-liposome and Re-188-DXR-liposome in normal tissues were generally similar to those from Re-188-BMEDA in intraperitoneal and intravenous administration. Tissue-absorbed dose in the liver was 0.24-0.40 and 0.17-0.26 (mGy/MBq) and in red marrow was 0.033-0.050 and 0.038-0.046 (mGy/MBq), respectively for Re-188-liposome and Re-188-DXR-liposome. Tumor-absorbed doses for the nanotargeted Re-188-liposome and Re-188-DXR-liposome were higher than those of Re-188-BMEDA for both routes of administration (4-26-fold). Dose to red marrow defined the recommended MAA. Conclusions: Our results suggest that radionuclide and chemoradiotherapeutic passive targeting delivery, using nanoliposomes as the carrier, is feasible and promising in systemic-targeted radionuclide therapy.
Date:
2008-12
Relation:
Cancer Biotherapy and Radiopharmaceuticals. 2008 Dec;23(6):749-758.