title: Preparation and characterization of a novel Al(18)F-NOTA-BZA conjugate for melanin-targeted imaging of malignant melanoma.
abstract: Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. Previous studies have demonstrated the specific binding ability of benzamide moiety to melanin. In this study, we developed a novel (18)F-labeled NOTA-benzamide conjugate, Al(18)F-NOTA-BZA, which can be synthesized in 30min with a radiochemical yield of 20-35% and a radiochemical purity of >95%. Al(18)F-NOTA-BZA is highly hydrophilic (logP=-1.96) and shows good in vitro stability. Intravenous administration of Al(18)F-NOTA-BZA in two melanoma-bearing mouse models revealed highly specific uptake in B16F0 melanotic melanoma (6.67±0.91 and 1.50±0.26%ID/g at 15 and 120min p.i., respectively), but not in A375 amelanotic melanoma (0.87±0.21 and 0.24±0.09%ID/g at 15 and 120min p.i., respectively). The clearance from most normal tissues was fast. A microPET scan of Al(18)F-NOTA-BZA-injected mice also displayed high-contrast tumor images as compared with normal organs. Owing to the favorable in vivo distribution of Al(18)F-NOTA-BZA after intravenous administration, the estimated absorption dose was low in all normal organs and tissues. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and thelow projected human dosimetry supported that Al(18)F-NOTA-BZA is a very promising melanin-specific PET probe for melanin-positive melanoma.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou, Taipei 11221, Taiwan.
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou, Taipei 11221, Taiwan; Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou, Taipei 11221, Taiwan.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Lo
authors.affiliation: Department of Nuclear Medicine, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Department of Nuclear Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Chih-Chieh
authors.initials: CC
authors.lastname: Shen
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou, Taipei 11221, Taiwan; Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, National Comprehensive Mouse Phenotyping and Drug Testing Center, Taipei, Taiwan; National PET/Cyclotron Center and Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou, Taipei 11221, Taiwan. Electronic address: hewang@ym.edu.tw.
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou, Taipei 11221, Taiwan. Electronic address: clchen2@ym.edu.tw.
authors.forename: Chuan-Lin
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D005462:Fluorine Radioisotopes / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution; D014184:Transplantation, Homologous
chemical_list: D001549:Benzamides; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D008543:Melanins; D019275:Radiopharmaceuticals; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; C037689:benzamide
keywords: Al–F complex; Benzamide; Melanoma; NOTA; Positron emission tomography