Document Detail


Tumor pretargeting in mice using MORF conjugated CC49 antibody and radiolabeled complimentary cMORF effector.
MedLine Citation:
PMID:  20639818     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: 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.
METHODS: 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.
RESULTS: 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 tumor was found to be less seriously reduced in vivo. In a pretargeting study under optimal conditions, both by imaging and by necropsy, the [(⁹⁹m)Tc]cMORF effector accumulated predominantly in the tumor of pretargeted mice. Normal tissue accumulations were minimal except in kidneys, liver, and a segment of intestines.
CONCLUSION: MORF pretargeting with CC49 was equally successful in the LS174T tumor model to the MORF pretargeting with MN14. The MORF-CC49 antibody may therefore be considered for future investigations toward early clinical trials.
Authors:
G Liu; S Dou; P H Pretorius; X Liu; L Chen; M Rusckowski; D J Hnatowich
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Publication Detail:
Type:  Journal Article     Date:  2009-12-15
Journal Detail:
Title:  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 Radiopharmaceutical Chemistry and Biology     Volume:  54     ISSN:  1824-4785     ISO Abbreviation:  Q J Nucl Med Mol Imaging     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-12-14     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101213861     Medline TA:  Q J Nucl Med Mol Imaging     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  333-40     Citation Subset:  IM    
Affiliation:
Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655-0243, USA. guozheng.liu@umassmed.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Neoplasm / administration & dosage*,  metabolism*
Drug Delivery Systems
Indium Radioisotopes / administration & dosage,  pharmacokinetics
Mice
Mice, Nude
Morpholines / administration & dosage*,  pharmacokinetics*
Morpholinos
Neoplasms, Experimental / metabolism*,  radiotherapy*
Radioimmunotherapy
Radiopharmaceuticals / administration & dosage,  pharmacokinetics
Technetium / administration & dosage,  pharmacokinetics
Tissue Distribution
Grant Support
ID/Acronym/Agency:
R01 CA094994-06/CA/NCI NIH HHS; R21 CA107360-02/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Neoplasm; 0/B72.3 antibody; 0/Indium Radioisotopes; 0/Morpholines; 0/Morpholinos; 0/Radiopharmaceuticals; 7440-26-8/Technetium
Comments/Corrections

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