Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||Hokkaido University (2007)|
Kyoto University (2005-2006)
KUGE Yuji Hokkaido University, Graduate school of Medicine, Professor (70321958)
SAJI Hideo Kyoto University, Graduate School of Pharmaceutical Sciences, Professor (40115853)
KIYONO Yasushi University of Fukui, Biomedical Imaging Research Center, Professor (50305603)
TAMAKI Nagara Hokkaido University, Graduate school of Medicine, Professor (30171888)
SEKI Koh-ichi Hokkaido University, Central Institute of Isotope Science, Professor (60094835)
UEDA Masashi Kyoto University, Graduate School of Medicine, Assistant Professor (40381967)
|Project Period (FY)
2005 – 2007
Completed (Fiscal Year 2007)
|Budget Amount *help
¥16,180,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥780,000)
Fiscal Year 2007: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2005: ¥10,600,000 (Direct Cost: ¥10,600,000)
|Keywords||Radioisotope / Cancer / Molecular imaging / Therapy|
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 therapy
In 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 therapy
The 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.