New PET /near IR-fluorescence tools for multimodal imaging in oncology

用于肿瘤学多模态成像的新型 PET/近红外荧光工具

• 批准号: 8906853
• 负责人: Richard Ting
• 金额: $ 23.8万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-12 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8906853
• 关键词: Address; Affect; Anti-CEA Antibody; Antibodies; Antineoplastic Agents; Behavior; Biodistribution; Blood - brain barrier anatomy; Breast cancer metastasis; Cancer Biology; Cancer Model; Cancer cell line; Characteristics; Charge; Clinical; Colorectal Cancer; Data; Databases; Development; Discipline of Nuclear Medicine; Drug Transport; Dyes; Extinction (Psychology); Fluorescence; Future; Generations; Genetic Engineering; Goals; Histology; Image; Integrins; Intracellular Transport; Label; Libraries; Ligands; Lymphatic; Malignant Neoplasms; Malignant neoplasm of brain; Mentors; Mind; Modality; Modification; Molecular; Molecular Weight; Monitor; Multimodal Imaging; Mus; Organ; PUVA Photochemotherapy; Patients; Peptide antibodies; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase III Clinical Trials; Positron-Emission Tomography; Preclinical Drug Evaluation; Process; Progress Reports; Property; Proteins; Publishing; Radiopharmaceuticals; Research; Resolution; Shapes; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Tracer; Training; Tumor Angiogenesis; Tumor Biology; Update; aqueous; blood vessel development; cancer imaging; design; direct application; experience; fluorophore; high throughput screening; imaging agent; imaging probe; in vivo; in vivo imaging; inhibitor/antagonist; molecular imaging; multimodality; novel; oncology; prevent; quantum; radiotracer; research study; small molecule; success; tool; tumor

SUMMARY/ABSTRACT - limit 30 lines – Richard Ting's K99/R00 application We have recently published the application of new 18F-PET/NIRF (Positron emission tomography/Near Infrared Fluorescence) multimodality imaging probes on the polydextran ligand Lymphoseek (tilmanocept, Neoprobe), a ligand currently in phase III clinical trials as a 99mTc labeled species for detecting lymphatic breast cancer metastasis. The K99 phase of this research applies this recent success to very different new molecules including peptides and proteins. We will apply the PET/NIRF probe to Angiopep 2, a 3 kD peptide for imaging drug transport across the blood brain barrier, and to 55 kD anti-CEA T84.66 diabody, a genetically engineered class of antibodies for imaging CEA positive tumors. These applications will allow us develop superior tracers for imaging colorectal cancer and drug transport. Another goal of the proposed K99 research is the generation of a library of different Integrin αvβ3 antagonists conjugated to PET/NIRF probes of differing molecular weights and charge. The imaging of this library will allow us to simultaneously select for the best probes for imaging tumor angiogenesis by PET and allow us to generate both PET and NIRF databases on the behavior of different moieties in vivo. This database would allow us to rationally design new drugs that accumulate in specific tissues (PET) while retaining the sub-cellular localization and inhibitory properties (observed by NIRF) for which they were selected. Data from the imaging of this library can be used to deliberately alter the in vivo biodistribution of new pharmaceuticals or select for probes that are specific for different forms of cancers. The first R00 phase aim attempts to advance PET/NIRF technology by exploiting the fact that fluorescence is the modality of choice for high-throughput drug screening, We will modify the cancer probes developed in the K99 with immobilizing technology to generate arrays that can indicate small changes in tumor biology, such as increased tumor aggressiveness, and help determine a patient's treatment regime. Desired compounds can be released from the array using aqueous 18F, to generate a PET probe, or combination of probes for corroborative in vivo imaging. The fluorophore on the array will then be substituted with photodynamic therapy (PDT) agents allowing for the selection of probes for PET guided endoscopic PDT applications. Finally, a new application that allows for kit-like radiotracer labeling will be applied to a new library of PET/NIRF small molecules that are capable of demonstrating intracellular transport. These molecules will possess exterior functionality that is similar to clinical 99mTc tracers in order to address the problem of recurring 99mTc shortages, a current problem in nuclear medicine today.

摘要/摘要 - 限制30行 - Richard Ting的K99/R00应用程序 我们最近发布了新的18F-PET/NIRF的应用（正电子发射） 层析成像/近红外荧光）多型配体上的多模式成像问题 淋巴糖（Tilmanocept，Neoprobe），这是一种目前正在III期临床试验中的配体，作为99mtc标记的物种 用于检测淋巴乳腺癌转移。 这项研究的K99阶段将最近的成功应用于非常不同的新分子 肽和蛋白质。我们将将PET/NIRF探针应用于Angiopep 2，一个3 kd的胡椒粉成像药物 穿过血脑屏障的运输，到55 kD抗CEA T84.66射击，这是一种基因工程的 成像CEA阳性肿瘤的抗体类别。这些应用程序将使我们发展出色 用于成像结直肠癌和药物运输的示踪剂。拟议的K99研究的另一个目标是 与PET/NIRF探针分化的不同整合素αVβ3拮抗剂的库的生成 分子量和电荷。该库的成像将使我们可以简单地选择最好的 通过PET对肿瘤血管生成进行成像的问题，并使我们能够在PET上产生PET和NIRF数据库 体内不同部分的行为。这个数据库将使我们能够合理设计新药 在保留亚细胞定位和抑制特性的同时，积聚在特定组织（PET）中 （由NIRF观察）选择它们。来自此库的成像的数据可用于 故意改变新药物的体内生物分布或选择特定的问题 不同形式的癌症。 第一个R00阶段AIM试图通过利用这样一个事实来推动PET/NIRF技术 荧光是高通量药物筛查的首选方式，我们将修改癌症问题 在K99中使用固定技术开发，以生成阵列，以表明很小的变化 肿瘤生物学，例如增加肿瘤侵袭性，并有助于确定患者的治疗方案。 可以使用18F水释放所需的化合物，以生成PET探针，或 佐证在体内成像中的问题的组合。阵列上的荧光团将是 用光动力疗法（PDT）代替，允许选择宠物的问题 内窥镜PDT应用。最后，将允许使用套件样的radiotracer标签的新应用程序 应用于能够证明细胞内的PET/NIRF小分子的新库 运输。这些分子将具有与临床99mtc示踪剂相似的外部功能 为了解决反复出现的99mTC短缺问题，这是当前核医学的一个问题。