Receptor Mediated SPECT Imaging Of Kaposi Sarcoma With 99mTc-Tilmanocept

 描述(由申请人提供)：Navidea BiopPharmticals已经开发出99mTC-tilmanocept，作为一种针对巨噬细胞甘露糖受体(CD206)的放射性药物诊断显像剂，用于辅助癌症手术中的淋巴测绘。2013年5月，美国食品和药物管理局批准了Navidea的新药申请(NDA)，将99mTc-Tilmanocept用于切除黑色素瘤和乳腺肿瘤的手术。这一SBIR Fast Track应用为99mTC-替马诺普提供了一种高度创新的新适应症。基于对HIV+(AIDS)患者卡波西肉瘤(KS)病变的99mTC-Tilmanocept的体外研究，Navidea与加州大学旧金山分校的McGrath&Maurer博士合作发现，所有KS病变细胞都表达CD206。KS病变可发生在艾滋病患者的肺部和胃肠道(GI)，构成严重的生命危险。及时和准确地识别这些KS内部病变对于提供可能显著延长KS艾滋病患者生命的治疗至关重要。目前的诊断方案是侵入性的，在准确识别KS内部病变方面面临挑战。我们的初步研究结果表明，99mTC-Tilmanocept可以更容易、更少侵入性和更准确地识别KS内部病变，从而改善KS患者的长期预后和护理质量。99mTC-Tilmanocept具有非凡的安全记录，没有观察到可归因于99mTc-Tilmanocept的重大不良事件。拟议工作的主要目标是证明，静脉注射99mTC-替马诺普可用作单光子发射计算机断层扫描(SPECT)显像剂，用于可视化和识别艾滋病患者的内部KS病变。此外，尽管过去20年在艾滋病治疗方面取得了非常重大的进展，但KS仍然是世界各地艾滋病患者的一种常见、严重和危及生命的疾病。迫切需要更好的治疗KS的方法。如果该项目成功，并且99mTc-tilmanocept被证明可以与KS皮损中的细胞特异性结合，将进行后续研究(不是本申请的一部分)，以确定tilmanocept是否可以用于靶向向KS皮损输送治疗药物。靶向给药可能会极大地提高疗效，为KS患者提供非常显着的额外好处。这一快速跟踪SBIR应用包括进行临床前动物研究，以检验静脉注射99mTC-替马诺普的安全性(第一部分)，然后进行临床研究，初步评估使用99mTC-替马诺普进行SPECT成像研究以识别人类患者内部KS病变的安全性和有效性(第二部分)。

 DESCRIPTION (provided by applicant): Navidea Biopharmaceuticals has developed 99mTc-tilmanocept as a radiopharmaceutical diagnostic imaging agent targeted to the macrophage mannose receptor (CD206) to be used as an aid for lymphatic mapping in cancer surgeries. The United States Food and Drug Administration approved Navidea's new drug application (NDA) for 99mTc-Tilmanocept for use in surgeries to remove melanomas and breast tumors in May of 2013. This SBIR Fast Track application proposes a highly innovative new indication for 99mTc-tilmanocept. Based on ex vivo work with 99mTc-Tilmanocept in Kaposi's sarcoma (KS) lesions from HIV+ (AIDS) patients, Navidea, in collaboration with Drs. McGrath & Maurer of the Univ of California-San Francisco have found th a t a ll KS lesion cells express CD206. KS lesions can occur in the lungs and along the gastrointestinal tract (GI) of AIDS patients where they pose a serious and life threatening risk. Timely and accurate identification of these internal KS lesions is essential for delivery of therapies that may significantly extend the lives of AIDS patients wit KS. Current diagnostic protocols are invasive and challenged to accurately identify internal KS lesions. Our preliminary findings indicated that 99mTc-Tilmanocept could be used to more easily, less invasively and more accurately identify internal KS lesions, thereby improving both the long term outcomes and quality of care for KS patients. 99mTc- Tilmanocept has an extraordinary safety record, with no significant adverse events attributable to 99mTc- tilmanocept having been observed. The primary goal for the proposed efforts is to demonstrate that 99mTc- tilmanocept when injected intravenously can be used as a single-photon emission computed tomography (SPECT) imaging agent for visualization and identification of internal KS lesions in AIDS patients. In addition, despite the very significant progress that has been made over the last two decades in AIDS therapies, KS remains a common, serious and life threatening condition in AIDS patients worldwide. Better therapies for KS are greatly needed. If this project is successful and 99mTc-tilmanocept is demonstrated to bind specifically to cells in KS lesions, follow on studies will be performed (not part of this application) to determine if tilmanocept can be used to target delivery of therapeutics to KS lesions. Targeted delivery of therapeutics may greatly improve their efficacies providing a very significant additional benefit t KS patients. This Fast Track SBIR application proposes preclinical animal studies examining the safety of intravenous injection of 99mTc-tilmanocept (part 1) followed by a clinical study providing the initial evaluation of the safety and efficacy of SPECT imaging studies with 99mTc-tilmanocept to identify internal KS lesions in human patients (part 2).