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: 8459516
• 负责人: Richard Ting
• 金额: $ 9万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459516
• 关键词: Address; Affect; Anti-CEA Antibody; Antibodies; Antineoplastic Agents; Behavior; Biodistribution; Blood - brain barrier anatomy; 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; Neoplasm Metastasis; Neoplasms in Vascular Tissue; Organ; Patients; Peptide antibodies; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase III Clinical Trials; Photochemotherapy; 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; cancer imaging; design; direct application; experience; fluorophore; high throughput screening; imaging probe; in vivo; inhibitor/antagonist; malignant breast neoplasm; molecular imaging; multimodality; novel; oncology; prevent; quantum; radiotracer; research study; small molecule; success; tool; tumor

DESCRIPTION (provided by applicant): 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 ?v?3 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 recurrin 99mTc shortages, a current problem in nuclear medicine today.

DESCRIPTION (provided by applicant): 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 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包括肽和蛋白质在内的非常不同的新分子。我们将将PET/NIRF探针应用于Angiopep 2，这是一种3 kD肽，用于在血脑屏障上成像传输药物，并将55 kD抗CEA T84.66 Dimody（用于成像CEA阳性肿瘤的基因工程抗体类别）。这些应用将使我们开发出用于成像结直肠癌和药物运输的优越的示踪剂。拟议的K99研究的另一个目标是产生不同整合素的文库？v？3拮抗剂与PET/NIRF探针不同的分子量和电荷的探针。该库的成像将使我们能够同时选择通过PET对肿瘤血管生成进行成像的最佳探针，并使我们能够就体内不同部分的行为产生PET和NIRF数据库。该数据库将使我们能够合理地设计积累在特定组织（PET）的新药，同时保留了亚细胞定位和抑制性能（由NIRF观察到）。该库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探针 针对不同形式的癌症。 第一个R00阶段AIM试图通过利用荧光是高通量药物筛查的选择的事实来推动PET/NIRF技术，我们将修改K99在K99中使用固定技术的癌症探针来产生阵列，这些阵列可以表明肿瘤生物学的较小变化，例如增加肿瘤侵袭性，并帮助确定患者的治疗状态。所需的化合物可以使用18F水性从阵列释放，以生成PET探针，也可以将探针组合用于体内成像中。然后，阵列上的荧光团将用光动力疗法（PDT）剂取代，允许选择宠物引导的内窥镜PDT应用探针。最后，一种允许套件样的放射性示意剂标记的新应用将应用于能够证明细胞内转运的PET/NIRF小分子的新库。这些分子将具有与临床99mTC示踪剂相似的外部功能，以解决recurrin 99mtc短缺的问题，这是当今核医学的当前问题。