title: A novel radiopharmaceutical for detection of malignant melanoma, based on melanin formation: 3-iodo-4-hydroxyphenyl-L-cysteine.
abstract: The aim of this study was to develop a new artificial amino acid radiopharmaceutical labelled with radioiodine for detection of malignant melanoma, based on melanin formation. By considering the affinity for tyrosinase, a starting enzyme on the branching point to melanin biosynthesis, 3-[125I]iodo-4-hydroxyphenyl-L-cysteine (125I-L-PC) was synthesized and evaluated biologically. Labelling of 125I-L-PC using the chloramine-T method was carried out conveniently and efficiently in a short period of time, with high specific activity. In a biodistribution study, 125I-L-PC showed a low accumulation in normal tissue and relative retention in B16 melanoma. A high contrast image of peripheral tumour was obtained during autoradiography. During an in vitro accumulation study, inhibition of 125I-L-PC with a tyrosinase inhibitor suggested interaction of this tracer with tyrosinase. It indicates that the uptake mechanism of 125I-L-PC to melanoma tissue was dependent on high tyrosinase activity in melanoma cells. Thus, 125I-L-PC appears to be a promising radioiodinated amino acid radiopharmaceutical for imaging malignant melanoma in relation to melanin formation, namely specific metabolism with high tyrosinase activity.
authors.affiliation: Department of Radiology, Miyazaki Medical College, 5200 Kihara, Kiyotake-cho, Miyazaki-gun, Miyazaki 889-1692, Japan. rnisii@post1.miyazaki-med.ac.jp
authors.forename: R
authors.initials: R
authors.lastname: Nishii
authors.forename: K
authors.initials: K
authors.lastname: Kawai
authors.forename: L
authors.initials: L
authors.lastname: Garcia Flores
authors.forename: H
authors.initials: H
authors.lastname: Kataoka
authors.forename: S
authors.initials: S
authors.lastname: Jinnouchi
authors.forename: S
authors.initials: S
authors.lastname: Nagamachi
authors.forename: Y
authors.initials: Y
authors.lastname: Arano
authors.forename: S
authors.initials: S
authors.lastname: Tamura
mesh_terms: D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007553:Isotope Labeling / Q000379:methods; D008543:Melanins / Q000096:biosynthesis*; D008545:Melanoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D012878:Skin Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014915:Whole-Body Counting
chemical_list: C481866:3-iodo-4-hydroxyphenylcysteine; D008543:Melanins; D019275:Radiopharmaceuticals; D003545:Cysteine