1. Development of 18F labeled tracers to visualize malignant melanoma
Malignant melanoma is one of the most lethal cancers because of its high systemic metastatic potential. Benzamide derivatives are known to have selective affinities with melanin and, over the past 2 decades, have been extensively investigated for the development of SPECT agents for melanoma detection. Thus we modified the structure of benzamide and labeled radionuclide 18F to develop a novel PET tracer to visualize malignant melanoma.
18F-labeled phosphonium cations accumulate to a higher degree in cardiomyocytes than in normal cells because of the higher mitochondrial membrane potential (MMP) in cardiomyocytes. This type of mitochondrial voltage sensor would be useful to detect myocardial abnormalities because loss of MMP is an early event in cell death caused by myocardial ischemia. Thus we developed several kinds of 18F-labeled phosphonium cations and reported in vivo characteristics.
3. Development of optimized synthetic module for routine [11C]acetate production
[11C]Acetate is quickly metabolized into acetyl-CoA in human cells and can enter the tricarboxylic acid cycle to participate in cell membrane lipid synthesis in tumor cells. Thus, [11C]acetate, a radiotracer for PET imaging, is under investigation for use in a number of cancers. we developed the optimized synthetic module and proved its high reproducibility and simplicity, with high radio chemical yield for routine clinical use.
A longer half-life (12.7 h) of 64Cu among positron emitters allows for imaging at later time points than 18F (half-life, 109.7 min) and is more appropriate for imaging of protein binders. Thus we optimized 64Cu labeling methods using 3 kinds of chelators (NOTA, DOTA, DTPA) and reported in vivo characteristics of artificial protein binder (repebody) which have high affinity for the epidermal growth factor receptor (EGFR).