Correlative Imaging of Tumor Angiogenesis

肿瘤血管生成的相关成像

• 批准号: 6806988
• 负责人: SANJIV S GAMBHIR
• 金额: $ 14.48万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6806988
• 关键词: angiogenesis; angiostatins; apoptosis; autoradiography; bioimaging /biomedical imaging; doxorubicin; immunocytochemistry; laboratory rabbit; monoclonal antibody; neoplasm /cancer blood supply; noninvasive diagnosis; perfusion; radionuclide imaging /scanning; radionuclides; single photon emission computed tomography; thallium; toxicology; vascular endothelium; vesicle /vacuole

DESCRIPTION (provided by applicant): In the R21 phase of this proposal we plan to develop new molecularly based imaging technologies for use as noninvasive markers of angiogenic endothelial cells and their death in response to treatment. Polymerized vesicles (PVs) chelated with radionuclide and coated with the monoclonal antibody directed against the alphavbeta3 integrin (antialphavbeta3-AbPVs) will be used as a molecular imaging agent for the detection of newly proliferating angiogenic endothelial cells in both untreated tumors and tumors treated with anti-angiogenic agents. In combination we will also evaluate regional tumor blood flow using the previously validated technique of thallium-201 perfusion imaging. We will determine the time course of tumoral and intratumoral localization of contrast in tumors using 99mTc-anti-alphavbeta3AbPVs and thallium-201 (tumor perfusion) uptake as seen with dual energy micro-SPECT (single photon emission computed tomography) radionuclide imaging. We will also perform immunohistochemistry for specific markers of angiogenesis and apoptosis and correlate these markers with changes in the localization of 99mTc-anti-alphaV beta3 AbPVs and thallium 201. The R33 phase of the program will be to non-invasively detect and quantify neovascularity (angiogenesis) and choose the best imaging regimen for angiogenesis based on these more advanced preclinical studies and develop synthesis and labeling protocols. We plan to perform pharmacokinetics and toxicology studies with preclinical materials and prepare an agent for gamma and SPECT imaging in clinical studies and file an IRB for cancer angiogenesis evaluation.

描述（由申请人提供）：在此提案的R21阶段，我们计划开发新的基于分子的成像技术，以用作血管生成内皮细胞的非侵入性标记，并将其死亡以应对治疗。用放射性核素螯合并用针对alphavbeta3整合蛋白（atialphavbeta3-abpvs）的单克隆抗体覆盖的聚合囊泡（PV）将用作分子成像剂，用于检测新近繁殖的血管生成性内膜细胞，并在两种繁殖的静脉内静脉内静脉内静脉内静脉内细胞。 - 血管生成剂。结合使用，我们还将使用先前经过验证的Thallium-201灌注成像技术评估区域肿瘤血流。我们将使用99mtc-anti-Alphavbeta3ABPVS和Thallium-201（肿瘤灌注）摄取（单光能微光谱（单光子光子计算机断层扫描）摄影），确定肿瘤和肿瘤内肿瘤内肿瘤内定位的时间过程。我们还将对血管生成和凋亡的特定标记进行免疫组织化学，并将这些标记与99MTC-ANTI-ALPHAV BETA3 ABPV和THALLIUM 201的定位变化相关。血管生成）并根据这些更先进的临床前研究选择最佳的血管生成成像方案，并制定合成和标记方案。我们计划使用临床前材料进行药代动力学和毒理学研究，并在临床研究中为伽马和SPECT成像做好准备，并为癌症血管生成评估提交IRB。