Presentation 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

Xie, Lin  ,  Fujinaga, Masayuki  ,  Yamasaki, Tomoteru  ,  Yui, Joji  ,  Shimoda, Yoko  ,  Hatori, Akiko  ,  Kumata, Katsushi  ,  Zhang, Yiding  ,  Nengaki, Nobuki  ,  Kawamura, Kazunori  ,  Ming-Rong, Zhang

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

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