Comparative dosimetric evaluation of nanotargeted (188)Re-(DXR)-liposome for internal radiotherapy

Cancer Biother Radiopharm. 2008 Dec;23(6):749-58. doi: 10.1089/cbr.2008.0489.

Abstract

A dosimetric analysis was performed to evaluate nanoliposomes as carriers of radionuclides ((188)Re-liposomes) and radiochemotherapeutic drugs [(188)Re-doxorubicin (DXR)-liposomes] in internal radiotherapy for colon carcinoma, as evaluated in mice.

Methods: Pharmacokinetic data for (188)Re-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), (188)Re-liposome, and (188)Re-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 doses derived from (188)Re-liposome and (188)Re-DXR-liposome in normal tissues were generally similar to those from (188)Re-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 (188)Re-liposome and (188)Re-DXR-liposome. Tumor-absorbed doses for the nanotargeted (188)Re-liposome and (188)Re-DXR-liposome were higher than those of (188)Re-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.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Ascites / diagnostic imaging
  • Ascites / radiotherapy*
  • Colonic Neoplasms / diagnostic imaging
  • Colonic Neoplasms / radiotherapy*
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanotechnology*
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / therapeutic use*
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use*
  • Radiotherapy Dosage
  • Rhenium / chemistry*
  • Tissue Distribution

Substances

  • Radiopharmaceuticals
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Rhenium
  • Doxorubicin