Abstract

This project was developed and is directed by C.H. Paik, Ph.D. The research has centered on improving the tumor-targeting property of monoclonal antibodies and the fragments by chemical modifications. For FY 2000 we have investigated the use of a novel multistep tumor targeting. Our strategy involves pretargeting tumors with monoclonal antibody (MoAb) peptide followed by the injection of a radiolabeled second peptide. This approach decouples the antibody injection from the radiolabel injection, thereby offering the specificity of antibody binding to tumor antigens while eliminating problems associated with slow blood clearance of radiolabeled MoAb due to its large size. This project involves the synthesis of MoAb-peptide conjugates, clearing agents, and radiolabeled peptides. We have been optimizing the synthesis of these reagents to maintain the integrity of the immunoreactivity of MoAb and allow dimerization formation of peptides. Our preliminary multistep tumor-targeting experiments using tumor-bearing nude mice showed high accumulation of a radiolabeled peptide in tumor tissues and low accumulation in non-tumor tissues and blood, thereby providing high tumor-to-background radioactivity ratios.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL002001-07
Application #
6431804
Study Section
(NMRR)
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Chakraborty, Mala; Wansley, Elizabeth K; Carrasquillo, Jorge A et al. (2008) The use of chelated radionuclide (samarium-153-ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing. Clin Cancer Res 14:4241-9
Chakraborty, Mala; Gelbard, Alexander; Carrasquillo, Jorge A et al. (2008) Use of radiolabeled monoclonal antibody to enhance vaccine-mediated antitumor effects. Cancer Immunol Immunother 57:1173-83
Khaibullina, Alfia; Jang, Beom-Su; Sun, Haihao et al. (2008) Pulsed high-intensity focused ultrasound enhances uptake of radiolabeled monoclonal antibody to human epidermoid tumor in nude mice. J Nucl Med 49:295-302
Barrett, Tristan; Koyama, Yoshinori; Hama, Yukihiro et al. (2007) In vivo diagnosis of epidermal growth factor receptor expression using molecular imaging with a cocktail of optically labeled monoclonal antibodies. Clin Cancer Res 13:6639-48
Hama, Yukihiro; Urano, Yasuteru; Koyama, Yoshinori et al. (2007) A target cell-specific activatable fluorescence probe for in vivo molecular imaging of cancer based on a self-quenched avidin-rhodamine conjugate. Cancer Res 67:2791-9
Zhang, YuJian; Xiang, Laiman; Hassan, Raffit et al. (2006) Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing mice. Clin Cancer Res 12:4695-701
Zhang, Meili; Yao, Zhengsheng; Zhang, Zhuo et al. (2006) The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter 211At, provides effective radioimmunotherapy for a murine model of leukemia. Cancer Res 66:8227-32
Dadachova, E; Park, C; Eberly, N et al. (2001) In vitro and in vivo characterization of 67Ga(3+) complexes with cis,cis-1,3,5-triamino-cyclohexane-N,N',N""-triacetic acid derivatives. Nucl Med Biol 28:695-701
Yao, Z; Garmestani, K; Wong, K J et al. (2001) Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody. J Nucl Med 42:1538-44
Kobayashi, H; Kao, C H; Kreitman, R J et al. (2000) Pharmacokinetics of 111In- and 125I-labeled antiTac single-chain Fv recombinant immunotoxin. J Nucl Med 41:755-62

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