Tumor targeting with radiolabeled antibodies in a human carcinoembryonic antigen transgenic mouse model

Szalai, G.; Williams, Lawrence E.; Primus, F. James

doi:10.1002/(sici)1097-0215(20000315)85:6<751::aid-ijc2>3.0.co;2-8

Cited by 2 publications

(1 citation statement)

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“…An important target for the detection and monitoring of the recurrence of colon cancer is the human carcinoembryonic antigen (CEA, CEACAM5), a key member of the family of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and a GPI-anchored cell surface glycoprotein that has been shown to be useful as a tumor-associated antigen and serum marker [3], [4]. The widely demonstrated overexpression of CEA in solid tumors can also be exploited to target tumor lesions by immunological methods [5] or for radioimmunotherapy (RIT) [6].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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PurposeColorectal 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.ProceduresMice 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. H&E staining, immunohistology, and autoradiography were performed to confirm the micro-CT and PET/MRI findings.ResultsPET/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.ConclusionWe 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.

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