利用18F标记的T84.66抗癌胚抗原双抗体对荷瘤小鼠的结直肠癌进行PET成像。

PET imaging of colorectal cancer in xenograft-bearing mice by use of an 18F-labeled T84.66 anti-carcinoembryonic antigen diabody.

作者信息

Cai Weibo, Olafsen Tove, Zhang Xianzhong, Cao Qizhen, Gambhir Sanjiv S, Williams Lawrence E, Wu Anna M, Chen Xiaoyuan

机构信息

Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, Stanford, California 94305-5484, USA.

出版信息

J Nucl Med. 2007 Feb;48(2):304-10.

PMID:17268029

Abstract

UNLABELLED

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.

摘要

未标记

在本研究中，我们研究了18F标记的抗癌胚抗原（CEA）T84.66双抗体，一种单链可变片段的基因工程非共价二聚体，用于对荷瘤小鼠中CEA表达进行小动物PET成像。

方法

用N-琥珀酰亚胺基-4-18F-氟苯甲酸酯（18F-SFB）实现抗CEA T84.66双抗体（分子量55 kDa）的18F标记。在荷皮下LS 174T人结肠癌和C6大鼠胶质瘤肿瘤的无胸腺裸鼠中评估18F-氟苄基-T84.66双抗体（18F-FB-T84.66双抗体）的生物分布。进行系列小动物PET成像研究以进一步评估体内靶向效能和药代动力学。

结果

从18F-SFB开始进行放射性标记需要35±5（平均±标准差）分钟，合成的示踪剂18F-FB-T84.66双抗体的比活为1.83±1.71 TBq/mmol。衰变校正后的放射化学产率为1.40%±0.16%（n = 4），放射化学纯度大于98%。放射免疫活性为57.1%±2.0%。在LS 174T异种移植模型中，小动物PET成像和生物分布研究均表明，18F-FB-T84.66双抗体显示出快速且高的肿瘤摄取以及从循环中快速清除。在注射18F-FB-T84.66双抗体后1小时即可获得高对比度的小动物PET图像，在CEA阴性的C6肿瘤中仅发现背景水平的活性积聚。该示踪剂主要通过肾脏清除，在早期时间点肝脏和脾脏中有一些活性。