P-cadherin is associated with a wide range of tumor types, making it an attractive therapeutic target. FF-21101 is a human–mouse chimeric monoclonal antibody (mAb) directed against human P-cadherin, which has been radioconjugated with indium-111 (111In) utilizing a DOTA chelator. We investigated the biodistribution of FF-21101(111In) in cynomolgus macaques and extrapolated the results to estimate internal radiation doses of111In- and yttrium-90 (90Y)-FF-21101 for targeted radioimmunotherapy in humans. Whole-body planar and SPECT imaging were performed at 0, 2, 24, 48, 72, 96, and 120 h post-injection, using a dual-head gamma camera. Volumes of interest of identifiable source organs of radioactivity were defined on aligned reference CT and serial SPECT images. Organs with the highest estimated dose values (mSv/MBq) for FF-21101(111In) were the lungs (0.840), spleen (0.816), liver (0.751), kidneys (0.629), and heart wall (0.451); and for FF-21101(90Y) dose values were: lungs (10.49), spleen (8.21), kidneys (5.92), liver (5.46), and heart wall (2.61). FF-21101(111In) exhibits favorable biodistribution in cynomolgus macaques and estimated human dosimetric characteristics. Data obtained in this study were used to support the filing of an investigational new drug application with the FDA for a Phase I clinical trial.
P-钙黏蛋白与多种肿瘤类型相关，使其成为具有吸引力的治疗靶点。FF-21101是一种针对人P-钙黏蛋白的人-鼠嵌合单克隆抗体，通过DOTA螯合剂与铟-111（¹¹¹In）进行放射性标记。本研究在食蟹猴中考察了FF-21101（¹¹¹In）的生物分布特征，并基于此结果推算了¹¹¹In-FF-21101与钇-90（⁹⁰Y）-FF-21101用于人类靶向放射免疫治疗时的内照射辐射剂量。使用双探头伽马相机在注射后0、2、24、48、72、96及120小时进行全身平面及SPECT显像。通过配准的参考CT图像与系列SPECT图像，对可识别的放射性源器官划定感兴趣区域。FF-21101（¹¹¹In）估算剂量值（mSv/MBq）最高的器官依次为：肺（0.840）、脾（0.816）、肝（0.751）、肾（0.629）及心壁（0.451）；而FF-21101（⁹⁰Y）的剂量值分别为：肺（10.49）、脾（8.21）、肾（5.92）、肝（5.46）和心壁（2.61）。FF-21101（¹¹¹In）在食蟹猴中表现出良好的生物分布特性及预估的人体剂量学特征。本研究获得的数据已用于支持向美国FDA提交新药临床试验申请，以开展I期临床试验。
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