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

Journal of Nuclear Medicine

Lawrence E. Williams¹  Anna M. Wu¹  Tove Olafsen¹  Xianzhong Zhang¹  Xiaoyuan Chen¹  Qizhen Cao¹  Sanjiv S. Gambhir¹  Weibo Cai¹ 

关键词: carcinoembryonic antigen (CEA);    T84.66 diabody;    ¹⁸F;    small-animal PET;    colorectal cancer;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown