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Pretargeting CWR22 prostate tumor in mice with MORF-B72.3 antibody and radiolabeled cMORF
Guozheng Liu1, Shuping Dou, P Hendrik Pretorius
1Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655-0243, USA. guozheng.liu@umassmed.edu
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.
Insights
The MORF/cMORF pretargeting technology successfully targeted CWR22 prostate tumors in mice. This method showed significant tumor accumulation of radiolabeled compounds, demonstrating its potential for prostate cancer imaging.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- The MORF/cMORF pretargeting system offers a novel approach for targeted delivery of radiopharmaceuticals.
- Prostate cancer diagnosis and treatment can benefit from improved molecular imaging techniques.
Purpose of the Study:
- To apply the MORF/cMORF pretargeting technology for targeting the CWR22 prostate tumor xenograft in nude mice.
- To evaluate the efficacy and specificity of this pretargeting approach in a relevant preclinical model.
Main Methods:
- Conjugation of anti-TAG-72 antibody B72.3 with MORF and radiolabeling of cMORF with 99mTc.
- In vitro confirmation of antibody binding specificity to CWR22 cells.
- In vivo administration of MORF-B72.3 followed by 99mTc-cMORF in tumor-bearing mice, with control groups receiving only radiolabeled cMORF or 111In-B72.3.
- Determination of maximum percent tumor accumulation (MPTA) and imaging via SPECT and planar gamma camera.
Main Results:
- CWR22 tumors were confirmed to be TAG-72-positive.
- MPTA of labeled cMORF in CWR22 tumors was 2.22%ID/g, significantly higher than the 0.12%ID/g in control mice.
- SPECT and planar imaging confirmed successful pretargeting of the CWR22 xenograft.
Conclusions:
- The MORF/cMORF pretargeting approach is effective for targeting the CWR22 prostate tumor xenograft.
- The observed MPTA in the CWR22 model was lower than in a previous LS174T model, potentially due to differences in tumor vascularization.
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