Comparison of 211At-PRIT and 211At-RIT of ovarian microtumors in a nude mouse model

Cancer Biother Radiopharm. 2013 Mar;28(2):108-14. doi: 10.1089/cbr.2012.1281. Epub 2012 Dec 11.

Abstract

Abstract Purpose: Pretargeted radioimmunotherapy (PRIT) against intraperitoneal (i.p.) ovarian microtumors using avidin-conjugated monoclonal antibody MX35 (avidin-MX35) and (211)At-labeled, biotinylated, succinylated poly-l-lysine ((211)At-B-PLsuc) was compared with conventional radioimmunotherapy (RIT) using (211)At-labeled MX35 in a nude mouse model.

Methods: Mice were inoculated i.p. with 1×10(7) NIH:OVCAR-3 cells. After 3 weeks, they received PRIT (1.0 or 1.5 MBq), RIT (0.9 MBq), or no treatment. Concurrently, 10 additional animals were sacrificed and examined to determine disease progression at the start of therapy. Treated animals were analyzed with regard to presence of tumors and ascites (tumor-free fraction; TFF), 8 weeks after therapy.

Results: Tumor status at baseline was advanced: 70% of sacrificed animals exhibited ascites. The TFFs were 0.35 (PRIT 1.0 MBq), 0.45 (PRIT 1.5 MBq), and 0.45 (RIT). The 1.5-MBq PRIT group exhibited lower incidence of ascites and fewer tumors >1 mm than RIT-treated animals.

Conclusions: PRIT was as effective as RIT with regard to TFF; however, the size distribution of tumors and presence of ascites indicated that 1.5-MBq PRIT was more efficient. Despite advanced disease in many animals at the time of treatment, PRIT demonstrated good potential to treat disseminated ovarian cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha Particles / therapeutic use*
  • Animals
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Astatine / administration & dosage*
  • Avidin / therapeutic use*
  • Disease Models, Animal*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Ovarian Neoplasms / diagnostic imaging
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / radiotherapy*
  • Radioimmunotherapy*
  • Radionuclide Imaging
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Avidin
  • Astatine