title: Synthesis and evaluation of ¹²³/¹³¹I-Iochlonicotinamide as a novel SPECT probe for malignant melanoma.
abstract: Malignant melanoma expresses a highly aggressive metastasis. Early diagnosis of malignant melanoma is important for patient survival. Radiolabeled benzamides and nicotinamides have been reported to be attractive candidates for malignant melanoma diagnosis as they bind to melanin, a characteristic substance that displays in malignant melanoma, and show high tumor accumulation and retention. Herein, we designed and synthesized a novel (123/131)I-labeled nicotinamide derivative that specifically binds to melanin. (123/131)I-Iochlonicotinamide was prepared with good radiochemical yield (50-70%, decay corrected) and high specific radioactivity (50-80 GBq/μmol). (131)I-Iochlonicotinamide exhibited good in vitro stability (radiochemical purity >95% after a 24-h incubation) in human serum. High uptake of (123/131)I-Iochlonicotinamide in B16F0 melanoma cells compared to that in A375 amelanotic cells demonstrated its selective binding to melanin. Intravenous administration of (123/131)I-Iochlonicotinamide in a melanoma-bearing mouse model revealed high uptake in melanotic melanoma and high tumor-to-muscle ratio. MicroSPECT scan of (123/131)I-Iochlonicotinamide injected mice also displayed high contrast tumor imaging as compared with normal organs. The radiation-absorbed dose projection for the administration of (131)I-Iochlonicotinamide to human was based on the results of biodistribution study. The effective dose appears to be approximately 0.44 mSv/MBq(-1). The specific binding of (123/131)I-Iochlonicotinamide to melanin along with a prolonged tumor retention and acceptable projected human dosimetry suggest that it may be a promising theranostic agent for treating malignant melanoma.
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou District, Taipei 11221, Taiwan.
authors: Chih-Chao
authors: CC
authors: Chang
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou District, Taipei 11221, Taiwan; Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
authors: Chih-Hsien
authors: CH
authors: Chang
authors: Department of Nuclear Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
authors: Chih-Chieh
authors: CC
authors: Shen
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou District, Taipei 11221, Taiwan.
authors: Chuan-Lin
authors: CL
authors: Chen
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou District, Taipei 11221, Taiwan; Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors: Ren-Shyan
authors: RS
authors: Liu
authors: Department of Nuclear Medicine, Taipei City Hospital, Zhongxiao Branch, No. 87, Tong-De Rd., Nan-Gang District, Taipei 11556, Taiwan. Electronic address: md317317@gmail.com.
authors: Ming-Hsien
authors: MH
authors: Lin
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Li-Nong St., Sec. 2, Pei-tou District, Taipei 11221, Taiwan. Electronic address: hewang@ym.edu.tw.
authors: Hsin-Ell
authors: HE
authors: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D015335:Molecular Probes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007457:Iodine Radioisotopes; D015335:Molecular Probes; D019275:Radiopharmaceuticals; D009536:Niacinamide
keywords: A375; B16F0; Benzamide; Melanoma; Nicotinamide