title: Molecular imaging of ectopic metabotropic glutamate 1 receptor in melanoma with a positron emission tomography radioprobe (18) F-FITM.
abstract: Oncoimaging using positron emission tomography (PET) with a specific radioprobe would facilitate individualized cancer management. Evidence indicates that ectopically expressed metabotropic glutamate 1 (mGlu1) receptor independently induces melanocyte carcinogenesis, and it is therefore becoming an important target for personalized diagnosis and treatment strategies for melanomas. Here, we report the development of an oncoprotein-based PET imaging platform in melanomas for noninvasive visualization and quantification of mGlu1 with a novel mGlu1-specific radioprobe, 4-(18)F-fluoro-N-[4-[6-(isopropyl amino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ((18)F-FITM). (18)F-FITM shows excellent pharmacokinetics, namely the dense and specific accumulation in mGlu1-positive melanomas versus mGlu1-negative hepatoma and normal tissues. Furthermore, the accumulation levels of radioactivity corresponded to the extent of tumor and to levels of mGlu1 protein expression in melanomas and melanoma metastasis. The (18)F-FITM PET imaging platform, as a noninvasive personalized diagnostic tool, is expected to open a new avenue for defining individualized therapeutic strategies, clinical trials, patient management and understanding mGlu1-triggered oncologic events in melanomas.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujinaga
authors.forename: Akiko
authors.initials: A
authors.lastname: Hatori
authors.forename: Tomoteru
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kumata
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Wakizaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Furutsuka
authors.forename: Makoto
authors.initials: M
authors.lastname: Takei
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Jin
authors.forename: Takako
authors.initials: T
authors.lastname: Furukawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013844:Thiazoles / Q000493:pharmacokinetics
chemical_list: C560416:4-fluoro-N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-N-methylbenzamide; D001549:Benzamides; D019275:Radiopharmaceuticals; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1
keywords: melanoma; metabotropic glutamate 1 receptor; oncoprotein; positron emission tomography; radioprobe