PET Imaging of Colorectal and Breast Cancer by Targeting EphB4 Receptor with 64Cu-Labeled hAb47 and hAb131 Antibodies

Journal of Nuclear Medicine

Ryan Park¹  Zanxian Xia¹  Zibo Li¹  Ren Liu¹  Parkash S. Gill¹  Jiacong Guo¹  Shuanglong Liu¹  Peter S. Conti¹  Dan Li¹  Hong Shan¹  Valery Krasnoperov¹ 

关键词: EphB4;    breast cancer;    colorectal cancer;    ⁶⁴Cu;    PET;   

DOI  :  10.2967/jnumed.112.116822

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Accumulating evidence suggests that ephrin type B receptor 4 (EphB4) plays a key role in the progression of numerous cancer types. In this study, we developed a series of 64Cu-labeled antibodies for PET imaging of tumor EphB4 expression. Methods: Anti-EphB4 antibodies (hAb47 and hAb131) were conjugated with the 64Cu-chelator DOTA through lysine, cysteine, or oligosaccharide on the antibody. DOTA-human IgG (hIgG) was also prepared as a control, which did not bind to EphB4. The EphB4 binding activity of these probes was evaluated through the bead-based binding assay with EphB4-alkaline phosphatase. The resulting PET probes were further evaluated in both HT29 (colorectal cancer) and MDA-MB-231 (breast cancer) xenografts. Results: All 3 conjugation methods retained most of the EphB4 binding activity of the antibodies (83.85% ± 3.82%, 76.25% ± 5.90%, 98.93% ± 3.75%, and 82.09% ± 4.14% for DOTA-Lys-hAb47, DOTA-Cys-hAb47, DOTA-Sug-hAb47, and DOTA-Lys-hAb131, respectively). Although DOTA-Sug-hAb47 demonstrated the highest receptor binding activity based on a EphB4 binding assay, the corresponding PET probe was trapped in the liver quickly in vivo. In HT29 xenografts, both 64Cu-DOTA-Lys-hAb47 and 64Cu-DOTA-Cys-hAb47 demonstrated prominent tumor accumulation, which reached a maximum at 48 h after injection (18.13 ± 1.73 percentage injected dose [%ID]/g and 11.81 ± 2.05 %ID/g, respectively). In contrast, 64Cu-DOTA-Lys-hIgG had a low tumor accumulation, thus demonstrating the target specificity of EphB4-antibody–based probes. Moreover, 64Cu-DOTA-Lys-hAb131 (29.48 ± 2.60 %ID/g) demonstrated significantly higher HT29 tumor accumulation than 64Cu-DOTA-Lys-hAb47. 64Cu-DOTA-Lys-hAb131 was also found to specifically accumulate in the MDA-MB-231 tumor model (12.96 ± 2.31 %ID/g). Conclusion: We have demonstrated that EphB4 can serve as a valid target for colorectal and breast cancer imaging. This approach would be valuable for evaluating disease course and therapeutic efficacy at the earliest stages of anti-EphB4 treatment. Moreover, these newly developed probes may have important applications in other cancer types overexpressing EphB4.

【 授权许可】

Unknown