Pretargeting CWR22 prostate tumor in mice with MORF-B72.3 antibody and radiolabeled cMORF
Department of Radiology, Division of Nuclear Medicine
Animals; Antibodies, Monoclonal; Cell Line, Tumor; Drug Delivery Systems; Male; Mice; Mice, Inbred BALB C; Morpholines; Prostatic Neoplasms; Radioimmunotherapy; Radiopharmaceuticals; Technetium; Treatment Outcome
Life Sciences | Medicine and Health Sciences
PURPOSE: We have now applied our MORF/cMORF pretargeting technology to the targeting of CWR22 prostate tumor in nude mice.
METHODS: The antiTAG-72 antibody B72.3 was conjugated with an 18 mer MORF while the cMORF was radiolabeled with (99m)Tc. The specific binding of the antibody to the CWR22 cells was first confirmed in an assay placing the radiolabeled B72.3 antibody in competition with increasing concentrations of native B72.3. Thereafter, a group of four CWR22 tumored mice intravenously received the MORF-B72.3 and, 3 days later, the (99m)Tc-cMORF, and were killed at 3 h postradioactivity injection. The dosage of the labeled cMORF was selected on the basis of previous experience in LS174T tumored mice. As controls, four animals received only the radiolabeled cMORF and another four received only the (111)In-B72.3. The maximum percent tumor accumulation (MPTA) of the labeled cMORF was subsequently determined by a dosage study of labeled cMORF. Both a multipinhole SPECT image and a planar gamma camera image were obtained of a representative mouse.
RESULTS: The CWR22 tumor was confirmed to be TAG-72-positive. The MPTA of the labeled cMORF in the CWR22 tumor was 2.22%ID/g compared to only 0.12%ID/g in control mice without pretargeting. Both the planar and tomographic images confirmed the success of the CWR22 pretargeting.
CONCLUSIONS: The MORF/cMORF pretargeting approach has been successfully applied to tumor targeting of the prostate xenograft CWR22. However, the MPTA in this tumor model is lower than that in the LS174T tumor model investigated earlier, possibly due to a lower tumor blood supply.
DOI of Published Version
Eur J Nucl Med Mol Imaging. 2008 Feb;35(2):272-80. Epub 2007 Oct 2. Link to article on publisher's site
European journal of nuclear medicine and molecular imaging
Liu, Guozheng; Dou, Shuping; Pretorius, P. Hendrik; Liu, Xinrong; Rusckowski, Mary; and Hnatowich, Donald J., "Pretargeting CWR22 prostate tumor in mice with MORF-B72.3 antibody and radiolabeled cMORF" (2007). Open Access Articles. 1255.