Molecular imaging and therapeutic efficacy of 188Re-(DXR)-liposome-BBN in AR42J pancreatic tumor-bearing mice

Oncol Rep. 2012 Nov;28(5):1736-42. doi: 10.3892/or.2012.1978. Epub 2012 Aug 22.

Abstract

Liposomes are good candidates as drug carriers and have been widely investigated in drug delivery systems. In this study, a new combination of bimodal 188Re-(DXR)-liposome-BBN radiochemotherapeutics was designed and studied for treating solid pancreatic tumor by intravenous administration. The in vivo nuclear microSPECT/CT imaging of tumor targeting, prolonged survival time and therapeutic efficacy were evaluated in AR42J malignant pancreatic solid tumor-bearing nude mice. MicroSPECT/CT imaging of 188Re-liposome-BBN pointed to significant targeting in tumors at 24 h after intravenous injection (SUV=2.13 ± 0.98). Co-injection of a blocking dose of cold BBN (4 mg/kg) inhibited the accumulation of 188Re-liposome-BBN in tumors (SUV=1.82 ± 0.31). For therapeutic efficacy, inhibition of tumor growth in mice treated with 188Re-DXR-liposome-BBN was precisely controlled [mean growth inhibition rate (MGI) = 0.092] and had longer survival time [life-span (LS) = 86.96%] than those treated with anticancer drug 188Re-liposome-BBN (MGI = 0.130; LS = 75%), Lipo-Dox-BBN (MGI = 0.666; LS = 3.61%) and untreated control mice. An additive tumor regression effect was observed (CI 0.946) for co-delivery of 188Re-DXR-liposome-BBN radiochemotherapeutics. These results point to the potential benefit of the 188Re-(DXR)-liposome-BBN radiochemotherapeutics for adjuvant cancer treatment with applications in oncology.

MeSH terms

  • Administration, Intravenous
  • Animals
  • Bombesin / pharmacology
  • Bombesin / therapeutic use*
  • Cell Line, Tumor
  • Chemoradiotherapy
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use*
  • Humans
  • Mice
  • Multimodal Imaging
  • Organometallic Compounds / pharmacology
  • Organometallic Compounds / therapeutic use
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / therapy*
  • Positron-Emission Tomography
  • Radiopharmaceuticals / pharmacology
  • Radiopharmaceuticals / therapeutic use
  • Rhenium / chemistry
  • Rhenium / pharmacology
  • Rhenium / therapeutic use*
  • Tissue Distribution
  • Tomography, X-Ray Computed
  • Xenograft Model Antitumor Assays

Substances

  • Organometallic Compounds
  • Radiopharmaceuticals
  • Rhenium
  • Doxorubicin
  • Bombesin