Radioimmunoimaging of Liver Metastases with PET Using a 64Cu-Labeled CEA Antibody in Transgenic MiceReportar como inadecuado




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Purpose

Colorectal cancer is one of the most common forms of cancer, and the development of novel tools for detection and efficient treatment of metastases is needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography PET imaging and radioimmunotherapy. Since carcinoembryonic antigen CEA is an important target in colorectal cancer, the CEA-specific M5A antibody has been extensively studied in subcutaneous xenograft models; however, the M5A antibody has not yet been tested in advanced models of liver metastases. The aim of this study was to investigate the 64Cu-DOTA-labeled M5A antibody using PET in mice bearing CEA-positive liver metastases.

Procedures

Mice were injected intrasplenically with CEA-positive C15A.3 or CEA-negative MC38 cells and underwent micro-computed tomography micro-CT to monitor the development of liver metastases. After metastases were detected, PET-MRI scans were performed with 64Cu-DOTA-labeled M5A antibodies. HandE staining, immunohistology, and autoradiography were performed to confirm the micro-CT and PET-MRI findings.

Results

PET-MRI showed that M5A uptake was highest in CEA-positive metastases. The %ID-cm3 16.5%±6.3% was significantly increased compared to healthy liver tissue 8.6%±0.9% and to CEA-negative metastases 5.5%±0.6%. The tumor-to-liver ratio of C15A.3 metastases and healthy liver tissue was 1.9±0.7. Autoradiography and immunostaining confirmed the micro-CT and PET-MRI findings.

Conclusion

We show here that the 64Cu-DOTA-labeled M5A antibody imaged by PET can detect CEA positive liver metastases and is therefore a potential tool for staging cancer, stratifying the patients or radioimmunotherapy.



Autor: Stefanie Nittka , Marcel A. Krueger , John E. Shively, Hanne Boll, Marc A. Brockmann, Fabian Doyon, Bernd J. Pichler, Michael Neu

Fuente: http://plos.srce.hr/



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