Development of Positron Emission Tomography Imaging by 64Cu-labeled Fab for Detecting ERC/mesothelin in a Mesothelioma Mouse Model

Background Malignant mesothelioma is a highlyaggressive form of cancer. Curative surgery is the onlyeffective therapy for mesothelioma, and therefore early diagnosis is important. However, early diagnosis is difficult using current diagnostic imaging techniques, and a new imaging method for early diagnosis is urgently required.We evaluated the affinity of radiolabeled monoclonal antibodies to the C-terminal fragment of ERC/mesothelin for this purpose.Methods 111 In-labeled or125 I-labeled IgG against C-terminal fragment of ERC and its Fab fragment were evaluated in vitro by cell binding, competitive inhibition, and cellular internalization assays, and in vivo by biodistribution in mice bearing ERC-expressing tumors. Next, the Fab fragment was labeled with the positron emitte 64 Cu and evaluated by positron emission tomography (PET).Results Radiolabeled IgG and Fab showed specific binding to ERC-expressing mesothelioma cells with high affinity. Both radiolabeled IgG and Fab internalized intocells after binding to ERC on the cell surface.111 In-labeled IgG accumulated in ERC-expressing tumors and resulted in a moderate tumor-to-blood ratio at 4 days after injection. Furthermore, PET using 64 Cu-labeled Fab visualized the tumor at 6 h after injection.Conclusion64Cu-labeled Fab can be useful for ERC-specific PET imaging, and can thus facilitate improved diagnosis of patients with early-stage mesothelioma. Nucl Med Commun 00:000–000 c 2010 Wolters Kluwer Health |Lippincott Williams & Wilkins