TAS::75 0849::TAS SBIR TOPIC 266 - PHASE II

迫切需要分子靶向显像剂来检测、分期和监测前列腺癌。前列腺膜特异性抗原（PSMA）是所有前列腺癌表达的一种膜糖蛋白。在该合同的第一阶段，我们重新设计了一种人源化psma特异性抗体，以提供纳米级生物靶向试剂。微体（~8-10 nm）比抗体小得多，但在体内传递和成像方面表现出显著改善的特性：完全结合结合快速的体内动力学。在I-124或Cu-64放射标记后，psma特异性小体在前列腺癌临床前模型中表现出良好的生物分布和微pet成像特性。在第二阶段，我们提出(1)优化huJ591小体的标记条件，使用残留和非残留放射性标记，并正式比较生物分布和成像性能，以确定huJ591小体临床使用的放射性标记策略。(2)进行小规模生产运行，并进行监管备案所需的测试和毒性研究。公共卫生相关性：一种新型纳米级显像剂已经开发出来，用于前列腺癌患者的特异性检测，目标是商业化。这些psma特异性小体的成功将为将这类工程生物分子用于其他体内纳米靶向策略奠定重要的基础。

Molecularly targeted imaging agents for the detection, staging, and monitoring of prostate cancer are urgently needed. Prostate Membrane Specific Antigen (PSMA) is a membrane glycoprotein expressed by all prostate cancer. In Phase I of this contract, we reengineered a humanized PSMA-specific antibody to provide a nanoscale biological targeting reagent. Minibodies (~8-10 nm) are significantly smaller than antibodies, yet exhibit dramatically improved properties for in vivo delivery and imaging: full binding combined with rapid in vivo kinetics. Following radiolabeling with I-124 or Cu-64, PSMA-specific minibodies demonstrated excellent biodistribution and microPET imaging properties in a preclinical model of prostate cancer. In Phase II we propose to (1) Optimize labeling conditions for the huJ591 minibody using both residualizing and non-residualizing radiolabels and formally compare biodistribution and imaging performance, in order to finalize the radiolabeling strategy for huJ591 minibody use clinically. (2) Perform a scale-down production run and conduct testing and toxicity studies required for regulatory filing. Public health relevance: A novel, nanoscale imaging agent has been developed for the specific detection of prostate cancer in patients with the goal of commercialization. Success of these PSMA-specific minibodies will establish important groundwork for using this class of engineered biomolecules for additional in vivo nanotargeting strategies.