Pharmacokinetics, micro-SPECT/CT imaging and therapeutic efficacy of (188)Re-DXR-liposome in C26 colon carcinoma ascites mice model

Nucl Med Biol. 2008 Nov;35(8):883-93. doi: 10.1016/j.nucmedbio.2008.09.005.

Abstract

The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ((188)Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality (188)Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o-->infinity)) of (188)Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of (188)Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated (188)Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after (188)Re-DXR-liposome (22.2 MBq of (188)Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of (188)Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P<.05) in mice than radiotherapeutics of (188)Re-liposome or chemotherapeutics of Lipo-Dox did. Therefore, intraperitoneal administration of novel (188)Re-DXR-liposome could provide a benefit and promising strategy for delivery of passive nanotargeted bimodality radiochemotherapeutics in oncology applications.

MeSH terms

  • Animals
  • Ascites / therapy*
  • Autoradiography
  • Colonic Neoplasms / diagnostic imaging
  • Colonic Neoplasms / therapy*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Drug Stability
  • Isotope Labeling
  • Male
  • Maximum Tolerated Dose
  • Mice
  • Mice, Inbred BALB C
  • Nanotechnology
  • Polyethylene Glycols / pharmacokinetics
  • Polyethylene Glycols / therapeutic use*
  • Radioisotopes / therapeutic use*
  • Rhenium / therapeutic use*
  • Tomography, Emission-Computed, Single-Photon*
  • Tomography, X-Ray Computed*

Substances

  • Radioisotopes
  • liposomal doxorubicin
  • Polyethylene Glycols
  • Rhenium
  • Doxorubicin