PMID: 20639818Jul 20, 2010Paper

Tumor pretargeting in mice using MORF conjugated CC49 antibody and radiolabeled complimentary cMORF effector.

The Quarterly Journal of Nuclear Medicine and Molecular Imaging : Official Publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of Radiopharmaceutica
Guozheng LiuDonald J Hnatowich

Abstract

Using the antiCEA antibody MN14, a LS174T mouse tumor model has been successfully targeted with (⁹⁹m)Tc for imaging and ¹⁸⁸Re for radiotherapy by phosphorodiamidate morpholino oligomers (MORF)/complementary MORF (cMORF) pretargeting strategy. This investigation evaluated the antiTAG-72 antibody CC49 as an alternative to MN14 for this application. Both CC49 and MN14 were labeled with ¹¹¹In via SCN-benzyl-DTPA and their biodistributions were compared to that of MN14 labeled via DTPA anhydride. Since the accessibility of the antibody to the effector is required for optimization of pretargeting, the internalization of both MORF-CC49 and MORF-MN14 antibodies in LS174T cells were evaluated in culture. In addition, the accessible concentration of MORF-CC49 antibody in tumor was determined in a series of pretargeting studies with escalating dosages of the [(⁹⁹m)Tc]cMORF effector. Finally, using these results and our semi-empirical model, an imaging study was performed under optimal pretargeting conditions. The biodistribution of ¹¹¹In to trace the MN14 antibody depended significantly on the labeling method. Furthermore, both MORF-CC49 and MORF-MN14 antibodies showed rapid internalization in culture. Fortunately, the accessibility in tu...Continue Reading

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