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Molecular imaging and strategies for cancer treatment: A Study to achieve noninvasive in vivo pathological evaluation by molecular imaging

分子影像与癌症治疗策略：通过分子影像实现无创体内病理评估的研究

基本信息

批准号：
17390332
负责人：
KUGE Yuji
金额：
$ 10.36万
依托单位：
Hokkaido University (2007)Kyoto University (2005-2006)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390332/
关键词：
Radioisotope Cancer Molecular imaging Therapy

项目摘要

Using positron emission tomography, we attempted to developed molecular imaging strategies that enable in vivo imaging of molecular mechanisms and/or characteristics of tumors, in order to contribute to personalized therapy of cancer patients. The results in the present study can be summarized as follows:1. Studies on molecular-targeted therapyIn our animal model, ^<18>F-FLT (a marker of DNA synthesis) can early detect the antiproliferative effects of the molecular-targeting therapy with gefitinib before significant changes in the tumor size, indicating the potential of FLT-PET in early monitoring of tumor response to the molecular-targeting therapy.2. Studies on radiation therapyThe results in an animal model indicated that post-radiation therapy response may be predicted by the accumulation of ^<18>F-FDG before complicated change, such as inflammation following irradiation, occurs.3. Development of molecular imaging probes that target molecular mechanisms of tumors.(1) For developing a thymidine phosphorylase (TP)-expression-based molecular imaging probe, we synthesized novel C-11 and I-123 labeled uracil derivatives, which were designed on the basis of one of the potent TP-inhibitors. The compounds synthesized possessed similar inhibitory potentials to the mother compounds.(2) A radioiodinated celecoxib derivative, ^<125I>-IMTP was synthesized. Our results showed a high inhibitory potency and selectivity of IMTP for COX-2, indicating its potential as a SPECT tracer for imaging cyclooxygenase-2 expression. In addition, we succeed to synthesizing a radioiodinated lumiracoxib derivative with reduced nonspecific bindings.(3) [^<99m>Tc-labeled anti-MT1-MMP (membrane-type-1 MMP) antibody accumulated in the tumor in time-dependent manner, indicating the potential of the labeled antibody for the imaging agent of tumor malignancy. In addition, the pre-targeting strategy improved S/N ratios.

使用正电子发射断层扫描，我们试图开发分子成像策略，使在体内成像的分子机制和/或肿瘤的特征，以有助于癌症患者的个性化治疗。本研究的主要结果如下：1.分子靶向治疗的研究在我们的动物模型中，<18>FLT-PET（DNA合成的标志物）可以在肿瘤大小发生显著变化之前早期检测到吉非替尼分子靶向治疗的抗增殖作用，表明FLT-PET在早期监测肿瘤对分子靶向治疗的反应方面具有潜力.放射治疗的研究动物模型的结果表明，在复杂的变化（如放射后的炎症）发生之前，可以通过~ 1F-FDG的积累来预测放射治疗后的反应<18>.开发针对肿瘤分子机制的分子成像探针。(1)为了开发一种基于胸苷磷酸化酶（TP）表达的分子成像探针，我们合成了新型的C-11和I-123标记的尿嘧啶衍生物，它们是基于一种有效的TP抑制剂而设计的。所合成的化合物具有与母体化合物相似的抑制潜力。(2)合成了一种放射性碘标记的塞来昔布衍生物，^<125I>-IMTP。我们的研究结果表明IMTP对考克斯-2具有高的抑制效力和选择性，表明其作为SPECT示踪剂用于成像环氧合酶-2表达的潜力。此外，我们成功地合成了一种放射性碘标记的罗美昔布衍生物，减少了非特异性结合。(3)抗<99m>MT 1-MMP（membrane-type-1 MMP）抗体在肿瘤内呈时间依赖性蓄积，提示该标记抗体有可能成为肿瘤恶性显像剂。此外，预瞄准策略改善了S/N比。