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Article
A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting and an antiTAG-72 antibody CC49
Information Technology Publications and Presentations
  • Guozheng Liu, University of Massachusetts Medical School
  • Shuping Dou, University of Massachusetts Medical School
  • Stephen P. Baker, University of Massachusetts Medical School
  • Ali Akalin, University of Massachusetts Medical School
  • Dengfeng Cheng, University of Massachusetts Medical School
  • Ling Chen, University of Massachusetts Medical School
  • Mary Rusckowski, University of Massachusetts Medical School
  • Donald J. Hnatowich, University of Massachusetts Medical School
UMMS Affiliation
Department of Radiology, Division of Nuclear Medicine; Information Services; Department of Pathology
Date
10-15-2010
Document Type
Article
Subjects
Colonic Neoplasms; Radioisotopes; Radiopharmaceuticals; Xenograft Model Antitumor Assays
Abstract
The utility of MORF/cMORF pretargeting for the radiotherapy of cancer requires further validation in tumored mice before clinical trials. We now report on a therapeutic study in mice pretargeted with MORF-CC49 (an anti-TAG-72 antibody CC49 conjugated with MORF, a phosphorodiamidate morpholino oligomer) and then targeted by 188Re-cMORF (a 188Re labeled complementary MORF). Before the dose-escalating therapeutic study, a pretargeting study in LS174T tumored mice was performed at tracer levels. By both necropsy and imaging, the tracer study showed that the whole body radioactivity was largely restricted to tumor in the mice pretargeted 48 h earlier with MORF-CC49 and the tumor radioactivity was retained over 90 h. After decay correction, a best-fit to the biodistribution provided the areas under the radioactivity curves (AUCs) used for the radiation dose estimates. The tumor to normal organ AUC ratios in all cases were greater than unity and ranged from 3 (kidneys) to 48 (muscle). Tumor growth was inhibited in the therapy study. At the highest 188Re dose of 1.40 mCi, a complete but temporary tumor remission was evident in 3 out of the 5 animals. Histological examination of tissues from these animals showed no evidence of cytotoxicity to normal tissues but obvious radiation damage to tumor. In conclusion, effective radiotherapy was achieved in a mouse model by MORF/cMORF pretargeting using 188Re as the therapeutic radionuclide and CC49 as the pretargeting antibody.
Rights and Permissions
Citation: Cancer Biol Ther. 2010 Oct 15;10(8):767-74. Link to article on publisher's site
Related Resources
Link to Article in PubMed
PubMed ID
21099368
Citation Information
Guozheng Liu, Shuping Dou, Stephen P. Baker, Ali Akalin, et al.. "A preclinical 188Re tumor therapeutic investigation using MORF/cMORF pretargeting and an antiTAG-72 antibody CC49" Vol. 10 Iss. 8 (2010) ISSN: 1538-4047 (Linking)
Available at: http://works.bepress.com/stephen_baker/97/