Biodistribution, Pharmacokinetic, and Imaging Studies with 186Re-labeled NR-LU-10 Whole Antibody in LS174T Colonie Tumor-bearing Mice

نویسندگان

  • M. H. Goldrosen
  • W. C. Biddle
  • J. Pancook
  • S. Bakshi
  • J-L. Vanderheyden
  • A. R. Fritzberg
  • A. C. Morgan
  • K. A. Foon
چکیده

Biodistribution, pharmacokinetic, and radioimaging studies were per formed with ""Re-labeled NR-LU-10 whole antibody in athymic nude mice bearing the LS174T tumor growing either s.c. or in an experimental hepatic metastasis model. NR-LU-10 is an IgG2b murine monoclonal antibody (MAb) that reacts with virtually all human tumors of epithelial origin. NR-BC-1, a IgG2b murine MAb that reacts with normal human B-cell and B malignancies, was used as an isotype-matched control. These MAbs were radiolabeled with IB*Re(3.7-day physical half-life; 1.07-MeV ßparticle and 137-keV y, 9% abundance) by a preformed chelate approach by using the triamide thiolate ligand system. ""'Re labeled NR-LU-10 (SO«iCi) was injected into nude mice bearing LS174T tumors growing s.c. Biodistribution studies revealed that the LS174T tumor retained the highest concentration of """Re-labeled NR-LU-10 (5.3% injected dose/g) at day 6. The tumorblood ratio ranged from 0.1:1 to 10.8:1 by day 6, the last day of analysis. In contrast the tumorblood ratio of '"Re-labeled NR-BC-1, the isotype-matched MAb control, was 1:1 on day 6. Pharmacokinetic analysis indicated that the f1/2ßof NRLU-10 for blood and other tissues ranged from 21 to 25 h, while the t, , ßfor the LS174T tumor averaged 52 h. The area under the curve for tumor compared to blood was 2.8to 5.7-fold higher than the area under the curve for all other tissues and organs. The mean residence time for NR-LU-10 in blood and all other organs ranged from 23 to 26 h, while the mean residence time for NR-LU-10 in the LS174T tumor was 72 h. Scintigraphic images revealed selective uptake of the '"''Re-labeled NRLU-10, but not of the '"Re-labeled NR-BC-1, at the LS174T tumor site. Studies in an experimental model of hepatic metastasis revealed a similar selective pattern of ""Re-labeled NR-LU-10 accumulation. Scintigraphic images of the I.SI 741 tumor growing within the athymic nude mouse liver were obtained. The biodistribution, pharmacokinetic, and scintigraphic image results suggest that ""Re-labeled NR-LU-10 shows prom ise as a therapeutic agent for gastrointestinal cancer.

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تاریخ انتشار 2006