title: Synthesis and in Vivo Evaluation of [123I]Melanin-Targeted Agents.
abstract: This study reports the synthesis, [(123)I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [(131)I]radiolabeled compounds for radionuclide therapy of melanoma. Radiolabeling was achieved via standard electrophilic iododestannylation in 60-90% radiochemical yield. Preliminary SPECT imaging demonstrated high and distinct tumor uptake of all compounds, as well as high tumor-to-background ratios compared to the literature compound [(123)I]4 (ICF01012). The most favorable compounds ([(123)I]20, [(123)I]23, [(123)I]41, and [(123)I]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [(123)I]20 and [(123)I]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [(123)I]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [(123)I]41 and [(123)I]53 to be the most favorable, displaying high and prolonged amounts of intact tracer in melanin containing tissues, suggesting melanin specific binding. Results herein suggest that compound [(123)I]53 displays favorable in vivo pharmacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [(131)I] therapeutic evaluation.
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Maxine P
authors.initials: MP
authors.lastname: Roberts
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Vu
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Ashford
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Berghofer
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Naomi A
authors.initials: NA
authors.lastname: Wyatt
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Anwen M
authors.initials: AM
authors.lastname: Krause-Heuer
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Tien Q
authors.initials: TQ
authors.lastname: Pham
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Taylor
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Leena
authors.initials: L
authors.lastname: Hogan
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Cathy D
authors.initials: CD
authors.lastname: Jiang
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Fraser
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Lengkeek
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Lidia
authors.initials: L
authors.lastname: Matesic
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gregoire
authors.affiliation: ‡Centre for Molecular Imaging, Peter MacCallum Cancer Centre, 12 St. Andrew's Place, East Melbourne, Victoria 3002, Australia.
authors.forename: Delphine
authors.initials: D
authors.lastname: Denoyer
authors.affiliation: ‡Centre for Molecular Imaging, Peter MacCallum Cancer Centre, 12 St. Andrew's Place, East Melbourne, Victoria 3002, Australia.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.affiliation: †LifeSciences Division, Australian Nuclear Science and Technology Organisation (ANSTO), Locked Bag 2001, Kirrawee DC, New South Wales 2232, Australia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
mesh_terms: D000818:Animals; D007457:Iodine Radioisotopes / Q000737:chemistry* / Q000627:therapeutic use*; D008543:Melanins / Q000737:chemistry*; D008545:Melanoma / Q000532:radiotherapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007457:Iodine Radioisotopes; D008543:Melanins