PO.ET08.02 · 实验与分子治疗
RT01：一种用于诊疗一体化精准肿瘤学的新型抗TF放射性核素药物偶联物（RDC）
RT01: A novel anti-TF, radionuclide drug conjugate (RDC) for theranostic precision oncology
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
组织因子（TF）是各种肿瘤的有吸引力治疗靶点。我们开发了RT01，一种同类首创的靶向放射诊疗一体化制剂，由一种人源化抗TF抗体偶联诊断用89Zr或治疗用177Lu放射性核素组成。在异种移植肿瘤模型中，SPECT/CT成像证明RT01-177Lu（单次200 μCi静脉剂量）快速且特异性地在肿瘤中蓄积，滞留超过6天并快速非靶清除（注射后4小时背景下降）。辐射强度摄取（%ID/cc）的肿瘤与肾比值超过9.2。这一单次200 μCi剂量注射的RT01-177Lu展现出强效抗肿瘤疗效和优异的耐受性。对十个主要器官（肾、肠、脑、肺、肝、股骨、脾、胃、心和胰腺）的组织病理学分析未显示可观察到的异常或严重毒性。总之，RT01诊疗一体化配对提供了卓越的肿瘤靶向、快速非靶清除和良好的毒性特征，支持其针对TF阳性癌症的持续临床开发。
查看英文原文 English abstract
Tissue Factor (TF) is an attractive therapeutic target for various tumors. We developed RT01, a first-in-class, targeted radio-theranostic agent consisting of a humanized anti-TF antibody conjugated to the diagnostic 89 Zr or therapeutic 177 Lu radionuclide. In a xenograft tumor model, SPECT/CT imaging demonstrated rapid and specific tumor accumulation of RT01-177 Lu (single 200μCi i.v. dose), with retention over 6 days and rapid non-target clearance (background decreased by 4 hours post-injection). The tumor-to-kidney ratio of radiation intensity uptake (%ID/cc) exceeded 9.2. This single 200μCi dose injection of RT01-177 Lu demonstrated potent anti-tumor efficacy and excellent tolerability. Histopathology analysis of ten major organs (kidney, intestine, brain, lung, liver, femur, spleen, stomach, heart, and pancreas) revealed no observable abnormalities or serious toxicity. In conclusion, the RT01 theranostic pair provides superior tumor targeting, rapid non-target clearance, and a favorable toxicity profile, supporting its continued clinical development for TF-positive cancers.
利益披露 Disclosure
E. Wu,
Nanolattix Employment.
Z. Qu,
Nanolattix Other, Founder and CEO.