@misc{oai:repo.qst.go.jp:00065682,
 author = {Xie, Lin and Fujinaga, Masayuki and Yamasaki, Tomoteru and Yui, Joji and Shimoda, Yoko and Hatori, Akiko and Kumata, Katsushi and Zhang, Yiding and Nengaki, Nobuki and Kawamura, Kazunori and Zhang, Ming-Rong and 謝 琳 and 藤永 雅之 and 山崎 友照 and 由井 譲二 and 下田 陽子 and 羽鳥 晶子 and 熊田 勝志 and 張 一鼎 and 念垣 信樹 and 河村 和紀 and 張 明栄},
 month = {Jun},
 note = {Objectives: Overexpression of metabotropic glutamate1 receptor (mGlu1) is found in brain and various cancers (1). Recently, we constructed the first mGlu1 oncoprotein-based PET platform with mGlu1-specific radioprobe 18F-FITM (2). However, 18F-FITM displayed high uptake of radioactivity both in brain and melanoma, which increased the risk of radiation-induced brain injury, then hampered its clinical application. In this study, using FITM as a lead compound, we developed a novel PET probe 4-iodo-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-11C-methyl- benzamide (11C-IITM) and explored its potential for melanoma imaging.
Methods: 11C-IITM was synthesized by N-11C-methylation of the desmethyl precursor with 11C-CH3OTf. In vitro binding affinity for mGlu1 was assayed. PET imaging and biodistribution were performed in the mice bearing B16F10 melanoma with rich mGlu1 expression.
Results: 11C-IITM was obtained with radiochemical yields of 20  5% (n > 10 based on 11C-CO2, EOS), radiochemical purity of >97%, and specific activity of 65–160 GBq/mol. PET showed high accumulation of radioactivity in target tumor (4.0 % ID/g) and very low uptake in non-target brain (0.9 % ID/g) in B16F10-bearing mice at 75 min after 11C-IITM injection. Ex vivo biodistribution confirmed the PET images and indicated better uptake ratio of tumor to brain in 11C-IITM (8.03 ± 0.46), compared with 18F-FITM (0.58 ± 0.05) at 90 min. In addition, the ratios of radioactivity for 11C-IITM in the tumor compared to blood, skin, and muscle at 90 min were 5-10. Treatment with  an mGlu1 selective ligand significantly reduced radioactive uptake in the tumor. 
Conclusions: 11C-IITM is a useful PET tracer for mGlu1 imaging in melanoma. This radioprobe can be further developed by 124I and 131I labeling for long-duration PET scan and radiotherapeutic usage., SNMMI 2015 Annual Meeting},
 title = {Developing 4-iodo-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N- 11C-methylbenzamide for imaging of metabotropic glutamate 1 receptor in melanoma},
 year = {2015}
}