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PET Imaging of Colorectal Cancer in Xenograft-Bearing Mice by Use of an ¹⁸F-Labeled T84.66 Anti–Carcinoembryonic Antigen Diabody

¹ Molecular Imaging Program at Stanford (MIPS) and Bio-X Program, Department of Radiology, Stanford University School of Medicine, Stanford, California; ² Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, California; ³ Department of Bioengineering, Stanford University School of Medicine, Stanford, California; and ⁴ Division of Radiology, City of Hope National Medical Center, Duarte, California

Correspondence: For correspondence or reprints contact: Xiaoyuan Chen, PhD, Molecular Imaging Program at Stanford (MIPS) and Bio-X Program, Department of Radiology, Stanford University School of Medicine, 1201 Welch Rd., P095, Stanford, CA 94305-5484. E-mail: shawchen{at}stanford.edu

In this study, we investigated the ¹⁸F-labeled anti–carcinoembryonic antigen (CEA) T84.66 diabody, a genetically engineered noncovalent dimer of single-chain variable fragments, for small-animal PET imaging of CEA expression in xenograft-bearing mice. Methods: ¹⁸F labeling of the anti-CEA T84.66 diabody (molecular mass, 55 kDa) was achieved with N-succinimidyl-4-¹⁸F-fluorobenzoate (¹⁸F-SFB). The biodistribution of the ¹⁸F-fluorobenzyl-T84.66 diabody (¹⁸F-FB-T84.66 diabody) was evaluated in athymic nude mice bearing subcutaneous LS 174T human colon carcinoma and C6 rat glioma tumors. Serial small-animal PET imaging studies were performed to further evaluate in vivo targeting efficacy and pharmacokinetics. Results: Radiolabeling required 35 ± 5 (mean ± SD) min starting from ¹⁸F-SFB, and the tracer ¹⁸F-FB-T84.66 diabody was synthesized with a specific activity of 1.83 ± 1.71 TBq/mmol. The decay-corrected radiochemical yield was 1.40% ± 0.16% (n = 4), and the radiochemical purity was greater than 98%. The radioimmunoreactivity was 57.1% ± 2.0%. The ¹⁸F-FB-T84.66 diabody showed rapid and high tumor uptake and fast clearance from the circulation in the LS 174T xenograft model, as evidenced by both small-animal PET imaging and biodistribution studies. High-contrast small-animal PET images were obtained as early as 1 h after injection of the ¹⁸F-FB-T84.66 diabody, and only a background level of activity accumulation was found in CEA-negative C6 tumors. The tracer exhibited predominantly renal clearance, with some activity in the liver and spleen at early time points. Conclusion: The ¹⁸F-labeled diabody represents a new class of tumor-specific probes for PET that are based on targeting cell surface antigen expression. The ¹⁸F-FB-T84.66 diabody can be used for high-contrast small-animal PET imaging of CEA-positive tumor xenografts. It may be translated to the clinic for PET of CEA-positive malignancies.

Key Words: carcinoembryonic antigen (CEA) • T84.66 diabody • ¹⁸F • small-animal PET • colorectal cancer

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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