@misc{oai:repo.qst.go.jp:00086417,
 author = {Lin, Xie and Masayuki, Hanyu and Masayuki, Fujinaga and Zhang, Lulu and Zhang, Yiding and Wakana, Mori and Kuan, Hu and Katsuyuki, Minegishi and Kotaro, Nagatsu and Kazunori, Kawamura and Zhang, Ming-Rong and Lin, Xie and Masayuki, Hanyu and Masayuki, Fujinaga and Zhang, Yiding and Wakana, Mori and Kuan, Hu and Katsuyuki, Minegishi and Kotaro, Nagatsu and Kazunori, Kawamura and Zhang, Ming-Rong},
 month = {Jun},
 note = {Objectives: Metabotropic glutamate receptor 1 (GRM1) is aberrantly overexpressed in a wide variety of human solid tumors, such as melanoma，but not in normal peripheral organs (1). Therefore, GRM1 can be a widely–applicable target for the theranostics in oncology. Here, a novel small-molecular radiopharmaceutical pair, 3-iodo- N-[4-[6-(methylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-[11C]methylbenzamide ([11C]1) and 3-211At-astato-N-[4-[6-(methylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([211At]1), was designed and developed to target the GRM1 for the theranostics in melanomas (Fig.1).  

Method: [ 11C]1 was synthesized by reacting a N-desmethyl precursor with [11C]CH3OTf in the presence of NaOH at room temperature for 5 min. Radiolabeling of [211At]1 was performed by reaction of aryl tin precursor with NCS-containing 211At/MeOH solution. The theranostic potentials of the radiopharmaceutical pair were explored for PET imaging and radiotherapy in GRM1-positive B16F10 melanoma-bearing mice.  

Results: [ 11C]1 and [211At]1 were obtained with a radiochemical purity of greater than 99% and radiochemical yields of 19 ± 8 % and 46 ± 3%, respectively, based on the total radioactivity of used radionuclides. In vivo PET imaging of [ 11C]1 clearly visualized the targeted melanomas with a good tumor-to-background contrast (Fig. 1A). Ex vivo biodistribution study verified the persistent increase of [ 11C]1, which reached 12.29 ± 2.44 %ID/g tissue at 90 min in the targeted melanomas, and rapidly cleared from nontarget organs after intravenous injection. In the therapeutic studies, [211At]1 exhibited unequivocal and durable antitumor efficacy with only a single treatment (2.96 MBq) in the melanoma model, compared to the controls (0.38 ± 0.02 cm3 vs. 7.88 ± 1.28 cm3 at 13 days post-therapy) (Fig. 1B). No decrease in body weight, and no liver and kidney damage were observed through the examination period in melanoma mice injected with 2.96 MBq of [211At]1. 

Conclusion: The novel small-molecular radiopharmaceutical pair successfully visualized the GRM1-positive melanomas by [ 11C]1 with high contrast PET images, and further treated by [211At]1 without significant toxicity. The results highlight the good potential of using [ 11C]1 and [211At]1 as theranostic agents for the management of GRM1-positive tumors and should be further investigated in the theranostic field of oncology in the clinic., SNMMI2022},
 title = {Theranostics of melanoma targeting metabotropic glutamate receptor 1 with a novel small-molecular radiopharmaceutical pair},
 year = {2022}
}