Intratumoral Administration of Rhenium-188-Labeled Pullulan Acetate Nanoparticles (PAN) in Mice Bearing CT-26 Cancer Cells for Suppression of Tumor Growth

  • Song, Ho-Chun (Department of Nuclear Medicine, Chonnam National University Hospital) ;
  • Na, Kun (Division of Biotechnology, The Catholic University of Korea) ;
  • Park, Keun-Hong (College of Medicine, Pochon CHA University, Cell and Gene Therapy Research Institute) ;
  • Shin, Chan-Ho (Department of Nuclear Medicine, Chonnam National University Hospital) ;
  • Bom, Hee-Seung (Department of Nuclear Medicine, Chonnam National University Hospital) ;
  • Kang, Dong-Min (Korea Basic Science Institute, Chuncheon Center) ;
  • Kim, Sung-Won (Biomedical Research Center, Korea Institute of Science and Technology) ;
  • Lee, Eun-Seong (Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah) ;
  • Lee, Don-Haeng (Department of Internal Medicine, Inha University)
  • Published : 2006.10.31

Abstract

The feasibility of pullulan acetate nanoparticles (PAN) with ionic strength (IS) sensitivity as a radioisotope carrier to inhibit tumor growth is demonstrated. PAN was radiolabeled with rhenium 188 (Re-188) without any chelating agents. The labeling efficiency of Re-188 into PAN (Re-188PAN) was $49.3{\pm}4.0%$ as determined by TLC. The tumor volumes of mice treated with 0.45 mCi of Re-188-PAN were measured and compared with that of free Re-188 after 5 days of intratumoral injection. For the histological evaluation of apoptotic nuclei of tumor cells, hematoxylin and eosin (H&E), and terminal deoxynucleotidyl transferase biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) staining were performed. The mean tumor volume of the Re-188-PAN-treated group was decreased by 36% after 5 days, whereas that the free Re-188-treated group was decreased by only 15% (P<0.05). The mean number of TUNEL-positive cells in Re-188-PAN-treated tumors at $144.3{\pm}79.9$ cells/section was significantly greater than the control ($26.7{\pm}7.9$ cells/section, P=0.03). The numbers of leukocyte and lymphocyte were decreased in both free Re-188- and Re-188-PAN-treated mice. These results indicated that the intratumoral injection of Re-188-PAN effectively inhibits the tumor growth by prolonging Re-188 retention time in tumor site induced by the IS sensitivity.

Keywords

References

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