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

摘要/摘要-限制30行-丁志强的K99/R00应用程序 我们最近发表了新的18F-PET/NIRF(正电子发射)的应用 聚葡聚糖配体的层析成像/近红外荧光多模式成像探针 Lymphoseek(tilmanocept，NeoProbe)，一种目前处于第三阶段临床试验的配体，作为99mTc标记物种 用于检测乳腺癌淋巴转移。 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，包括 多肽和蛋白质。我们将把PET/NIRF探针应用于Angiopep 2，一种用于药物成像的3kD多肽 转运通过血脑屏障，并向55kD的抗CEA T84.66糖尿病，一种基因工程 用于CEA阳性肿瘤成像的抗体类别。这些应用程序将使我们能够开发出更好的 用于结直肠癌成像和药物转运的示踪剂。拟议的K99研究的另一个目标是 不同整合素αvβ_3拮抗剂与不同类型的pET/nIRF探针结合文库的构建 分子量和电荷。这个图书馆的图像将允许我们同时选择最好的 用正电子发射计算机断层扫描成像肿瘤血管生成的探针，并允许我们在 在活体内不同部分的行为。这个数据库将允许我们合理地设计新药 在特定组织中蓄积(PET)，同时保留亚细胞定位和抑制特性 (由NIRF观察)，他们被选中。来自该库成像的数据可用于 故意改变新药物在体内的生物分布或选择特异性的探针 不同形式的癌症。 第一个R00阶段的AIM试图通过利用以下事实来推进PET/NIRF技术 荧光是高通量药物筛选的首选手段，我们将对癌症探针进行修改 在K99中开发，使用固定技术生成数组，可以指示 肿瘤生物学，如肿瘤侵袭性增加，并帮助确定患者的治疗方案。 可以使用水18F从阵列中释放所需的化合物，以产生PET探针，或者 用于体内确证成像的探针组合。然后阵列上的荧光团将是 取而代之的是光动力疗法(PDT)试剂，允许选择用于PET引导的探针 内窥镜下光动力疗法的应用。最后，一种允许像试剂盒一样标记放射性示踪剂的新应用程序将是 应用于一个新的能够展示细胞内的PET/NIRF小分子文库 运输。这些分子将按顺序具有类似于临床99mTc示踪剂的外部功能 以解决反复出现的99mTc短缺问题，这是当今核医学中的一个当前问题。

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.