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Erschienen in: Tumor Biology 3/2012

01.06.2012 | Research Article

Pretargeting: taking an alternate route for localizing radionuclides

verfasst von: Robert M. Sharkey, Chien-Hsing Chang, Edmund A. Rossi, William J. McBride, David M. Goldenberg

Erschienen in: Tumor Biology | Ausgabe 3/2012

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Abstract

Bispecific antibody pretargeting is a two-step procedure for selectively delivering radionuclides to tumors. The procedure was developed to solve a number of problems encountered when radionuclides are directly coupled to an IgG, such as slow blood clearance and delayed tumor accretion. While various forms of antibody fragments can reduce blood pool activity and provide faster tumor localization, tumor uptake is reduced considerably. In pretargeting procedures, the radionuclide is attached to a small molecule that quickly traverses the vascular barrier to reach the tumor cells, achieving maximum accretion within 0.5 to 1.0 h. Just as quickly, it is eliminated from the body, thereby minimizing tissue exposure and developing high tumor/tissue ratios very early. In order to capture the radionuclide in the tumor, a bispecific antibody (bsMAb) that binds to the tumor and to the isotope carrier (e.g., a hapten-peptide) is pre-administered some time earlier. The pretargeting procedure has been shown repeatedly to improve tumor localization as compared to directly radiolabeled antibodies, thereby enhancing both imaging and therapy. In this article, we review the progress our group has made toward developing and testing bsMAb pretargeting systems for cancer detection and therapy.
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Zurück zum Zitat Schoffelen R, Boerman OC, van der Graff WT, van Herpen CM, Sharkey RM, McBride WJ, Chang CH, Rossi EA, Goldenberg DM, Oyen WJ. Phase I clinical study of the feasibility of pretargeted radioimmunotherapy (PT-RAIT) in patients with colorectal cancer (CRC): first results. J Nucl Med. 2011;52:107 (abstr 358).CrossRef Schoffelen R, Boerman OC, van der Graff WT, van Herpen CM, Sharkey RM, McBride WJ, Chang CH, Rossi EA, Goldenberg DM, Oyen WJ. Phase I clinical study of the feasibility of pretargeted radioimmunotherapy (PT-RAIT) in patients with colorectal cancer (CRC): first results. J Nucl Med. 2011;52:107 (abstr 358).CrossRef
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Zurück zum Zitat Schoffelen R, van der Graaf WT, Franssen G, Sharkey RM, Goldenberg DM, McBride WJ, Rossi EA, Eek A, Oyen WJ, Boerman OC. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice. J Nucl Med. 2010;51:1780–7.PubMedCrossRef Schoffelen R, van der Graaf WT, Franssen G, Sharkey RM, Goldenberg DM, McBride WJ, Rossi EA, Eek A, Oyen WJ, Boerman OC. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice. J Nucl Med. 2010;51:1780–7.PubMedCrossRef
Metadaten
Titel
Pretargeting: taking an alternate route for localizing radionuclides
verfasst von
Robert M. Sharkey
Chien-Hsing Chang
Edmund A. Rossi
William J. McBride
David M. Goldenberg
Publikationsdatum
01.06.2012
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 3/2012
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0367-6

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