使用 124I-抗 CD20 scFv 二聚体(双抗体)进行 B 细胞淋巴瘤免疫 PET 成像。
ImmunoPET imaging of B-cell lymphoma using 124I-anti-CD20 scFv dimers (diabodies).
机构信息
Department of Molecular and Medical Pharmacology, UCLA Crump Institute for Molecular Imaging, Los Angeles, CA 90095, USA.
出版信息
Protein Eng Des Sel. 2010 Apr;23(4):243-9. doi: 10.1093/protein/gzp081. Epub 2010 Jan 6.
Rapid clearing engineered antibody fragments for immunoPET promise high sensitivity at early time points. Here, tumor targeting of anti-CD20 diabodies (scFv dimers) for detection of low-grade B-cell lymphomas were evaluated. In addition, the effect of linker length on oligomerization of the diabody was investigated. Four rituximab scFv variants in the V(L)-V(H) orientation with different linker lengths between the V domains (scFv-1, scFv-3, scFv-5, scFv-8), plus the scFv-5 with a C-terminal cysteine (Cys-Db) for site-specific modification were generated. The scFv-8 and Cys-Db were radioiodinated with (124)I for PET imaging, and biodistribution of (131)I-Cys-Db was carried out at 2, 4 10 and 20 h. The five anti-CD20 scFv variants were expressed as fully functional dimers. Shortening the linker to three or one residue did not produce higher order of multimers. Both (124)I-labeled scFv-8 and Cys-Db exhibited similar tumor targeting at 8 h post injection, with significantly higher uptakes than in control tumors (P < 0.05). At 20 h, less than 1% ID/g of (131)I-labeled Cys-Db was present in tumors and tissues. Specific tumor targeting and high contrast images were achieved with the anti-CD20 diabodies. These agents extend the repertoire of reagents that can potentially be used to improve detection of low-grade lymphomas.
快速清除工程抗体片段用于 immunoPET 有望在早期获得高灵敏度。在这里,评估了用于检测低级别 B 细胞淋巴瘤的抗 CD20 二价体(scFv 二聚体)的肿瘤靶向性。此外,还研究了接头长度对二价体寡聚化的影响。在 V(L)-V(H)方向上生成了四种具有不同 V 结构域之间接头长度的利妥昔单抗 scFv 变体(scFv-1、scFv-3、scFv-5、scFv-8),以及带有 C 末端半胱氨酸(Cys-Db)用于特异性修饰的 scFv-5。scFv-8 和 Cys-Db 用 (124)I 放射性碘标记用于 PET 成像,并在 2、4、10 和 20 h 进行 (131)I-Cys-Db 的生物分布。五种抗 CD20 scFv 变体均表达为完全功能的二聚体。将接头缩短至三个或一个残基不会产生更高阶的多聚体。(124)I 标记的 scFv-8 和 Cys-Db 在注射后 8 小时显示出相似的肿瘤靶向性,与对照肿瘤相比摄取率显著更高(P < 0.05)。在 20 小时时,(131)I 标记的 Cys-Db 在肿瘤和组织中的含量不到 1% ID/g。抗 CD20 二价体实现了特异性肿瘤靶向和高对比度图像。这些试剂扩展了潜在可用于提高低级别淋巴瘤检测的试剂库。