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DOTA螯合剂对异种移植小鼠体内镥标记和钇标记利妥昔单抗的放射化学纯度及生物分布的影响

Influence of DOTA Chelators on Radiochemical Purity and Biodistribution of Lu- and Y-Rituximab in Xenografted Mice.

作者信息

Karczmarczyk Urszula, Wojdowska Wioletta, Mikołajczak Renata, Maurin Michał, Laszuk Ewa, Garnuszek Piotr

机构信息

National Centre for Nuclear Research, Radioisotope Centre POLATOM, Otwock, Poland.

出版信息

Iran J Pharm Res. 2018 Fall;17(4):1201-1208.

PMID:30568680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6269569/
Abstract

This work presents a comparative biological evaluation of Y- and Lu- labelled DOTA-SCN and DOTA-NHS conjugated to Rituximab in tumour-bearing mice. Two DOTA derivatives, p-SCN-Bn-DOTA and DOTA-NHS-ester were conjugated to Rituximab and then freeze-dried kit formulations were prepared, as previously described (1). Tissue distribution was investigated in tumour-bearing (Raji s.c.) male Rj: NMRI-Foxn1/Foxn1 mice at different time points after administration of Lu-DOTA-Rituximab or Y-DOTA-Rituximab (6 MBq/10 μg per mouse). In addition, tumour images were acquired with a PhotonIMAGER after injection of Y-DOTA (SCN)-Rituximab. All radioimmunoconjugates were obtained with high radiolabelling yield (RCP > 98%) and specific activity of ca. 0.6 GBq/mg. The conjugates were stable in human serum and in 0.9% NaCl; however, progressive aggregation was observed with time, in particular for DOTA -(SCN) conjugates. Both Lu- and Y-DOTA -(SCN)-Rituximab revealed slow blood clearance. The maximum tumour uptake was found 72 h after injection of Lu-DOTA -(SCN)-Rituximab (9.3 ID/g). A high radioactivity uptake was observed in liver and spleen, confirming the hepatobiliary excretion route. The results obtained by the radioactive optical imaging harmonize with those from the biodistribution study.

摘要

本研究对荷瘤小鼠体内与利妥昔单抗偶联的钇（Y）和镥（Lu）标记的DOTA-SCN及DOTA-NHS进行了比较生物学评价。将两种DOTA衍生物，对氨基硫脲苄基-DOTA（p-SCN-Bn-DOTA）和DOTA-NHS-酯与利妥昔单抗偶联，然后按照之前描述的方法（1）制备冻干试剂盒制剂。在给荷瘤（皮下接种Raji细胞）的雄性Rj:NMRI-Foxn1/Foxn1小鼠注射Lu-DOTA-利妥昔单抗或Y-DOTA-利妥昔单抗（每只小鼠6 MBq/10 μg）后的不同时间点，研究其组织分布。此外，注射Y-DOTA-(SCN)-利妥昔单抗后，用PhotonIMAGER采集肿瘤图像。所有放射免疫偶联物的放射性标记产率均很高（放射化学纯度>98%），比活度约为0.6 GBq/mg。这些偶联物在人血清和0.9%氯化钠溶液中稳定；然而，随着时间的推移观察到有逐渐聚集的现象，特别是对于DOTA-(SCN)偶联物。Lu-DOTA-(SCN)-利妥昔单抗和Y-DOTA-(SCN)-利妥昔单抗的血液清除均较慢。注射Lu-DOTA-(SCN)-利妥昔单抗后72小时发现肿瘤摄取量最大（9.3 ID/g）。在肝脏和脾脏中观察到高放射性摄取，证实了肝胆排泄途径。放射性光学成像获得的结果与生物分布研究的结果一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4be6/6269569/45b262dff10d/ijpr-17-1201-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4be6/6269569/0e24bf0d1629/ijpr-17-1201-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4be6/6269569/45b262dff10d/ijpr-17-1201-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4be6/6269569/0e24bf0d1629/ijpr-17-1201-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4be6/6269569/45b262dff10d/ijpr-17-1201-g002.jpg

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Curr Radiopharm. 2015;8(1):62-8. doi: 10.2174/1874471008666141215151253.
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Absorption reconstruction improves biodistribution assessment of fluorescent nanoprobes using hybrid fluorescence-mediated tomography.吸收重建利用混合荧光介导断层扫描改善了荧光纳米探针的生物分布评估。
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