In Vivo Biodistribution and Lifetime Analysis of Cy5.5-Conjugated Rituximab in Mice Bearing Lymphoid Tumor Xenograft Using Time-Domain Near-Infrared Optical Imaging
In Vivo Biodistribution and Lifetime Analysis of Cy5.5-Conjugated Rituximab in Mice Bearing Lymphoid Tumor Xenograft Using Time-Domain Near-Infrared Optical Imaging
复制标题
DOI：
10.2310/7290.2008.00028
复制
发表时间：
2008-11-01
影响因子：
2.8
通讯作者：
Lorusso, Vito
中科院分区：
文献类型：
--
作者：
Biffi, Steania;Garrovo, Chiara;Lorusso, Vito
利妥昔单抗是一种针对人 CD20 抗原的嵌合单克隆抗体，该抗原在 B 细胞淋巴细胞和大多数 B 细胞淋巴恶性肿瘤上表达。在此，我们报告了利妥昔单抗与近红外 (NIR) 荧光团 Cy5.5 (RI-Cy5.5) 的缀合物作为体外、体内和离体 NIR 时域 (TD) 光学成像的工具。在体外，RI-Cy5.5 保留了生物活性，并导致肿瘤细胞上的细胞相关荧光升高。在体内，注射到患有淋巴瘤的小鼠体内的 RI-Cy5.5 的 TD 光学成像分析显示，肿瘤摄取缓慢，并且探针在肿瘤内具有特定的持久性。进行腹膜内和静脉内给药后的生物分布研究以评估肿瘤摄取的差异。腹腔注射后器官中的RI-Cy5.5浓度没有静脉内注射后那么高。通过TD光学成像和免疫组织化学对生物组织和器官进行的离体分析证实了探针的分布，如体内成像实验所证明的那样，表明RI-Cy5.5选择性地积聚在肿瘤组织和主要排泄器官中。总之，该研究表明 NIR TD 光学成像是利妥昔单抗靶向研究的强大工具，可进一步了解其在淋巴瘤治疗中的给药结果。
Rituximab is a chimeric monoclonal antibody directed against human CD20 antigen, which is expressed on B-cell lymphocytes and on the majority of B-cell lymphoid malignancies. Herein we report the conjugate of rituximab with the near-infrared (NIR) fluorophore Cy5.5 (RI-Cy5.5) as a tool for in vitro, in vivo, and ex vivo NIR time-domain (TD) optical imaging. In vitro, RI-Cy5.5 retained biologic activity and led to elevated cell-as sociated fluorescence on tumor cells. In vivo, TD optical imaging analysis of RI-Cy5.5 injected into lymphoma-bearing mice revealed a slow tumor uptake and a specific long-lasting persistence of the probe within the tumor. Biodistribution studies after intraperitoneal and endovenous administration were undertaken to evaluate differences in the tumor uptake. RI-Cy5.5 concentration in the organs after intraperitoneal injection was not as high as after endovenous injection. Ex vivo analysis of biologic tissues and organs by both TD optical imaging and immunohistochemistry confirmed the probe distribution, as demonstrated by imaging experiment in vivo, showing that RI-Cy5.5 selectively accumulated in the tumor tissue and major excretion organs. In summary, the study indicates that NIR TD optical imaging is a powerful tool for rituximab-targeting investigation, furthering understanding of its administration outcome in lymphoma treatment.