Synthesis and in vivo evaluation of [123I]melanin-targeted agents

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dc.contributor.authorRoberts, MPen_AU
dc.contributor.authorNguyen, VHen_AU
dc.contributor.authorAshford, MEen_AU
dc.contributor.authorBerghofer, PJen_AU
dc.contributor.authorWyatt, NAen_AU
dc.contributor.authorKrause-Heuer, AMen_AU
dc.contributor.authorPham, TQen_AU
dc.contributor.authorTaylor, SRen_AU
dc.contributor.authorHogan, Len_AU
dc.contributor.authorJiang, CDen_AU
dc.contributor.authorFraser, BHen_AU
dc.contributor.authorLengkeek, NAen_AU
dc.contributor.authorMatesic, Len_AU
dc.contributor.authorGrégoire, MCen_AU
dc.contributor.authorDenoyer, Den_AU
dc.contributor.authorHicks, RJen_AU
dc.contributor.authorKatsifis, Aen_AU
dc.contributor.authorGreguric, Ien_AU
dc.date.accessioned2020-03-29T20:29:30Zen_AU
dc.date.available2020-03-29T20:29:30Zen_AU
dc.date.issued2015-08-15en_AU
dc.date.statistics2020-03-20en_AU
dc.description.abstractThis study reports the synthesis, [123I]radiolabeling, and biological profile of a new series of iodinated compounds for potential translation to the corresponding [131I]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 [123I]4 (ICF01012). The most favorable compounds ([123I]20, [123I]23, [123I]41, and [123I]53) were selected for further biological investigation. Biodistribution studies indicated that all four compounds bound to melanin containing tissue with low in vivo deiodination; [123I]20 and [123I]53 in particular displayed high and prolonged tumor uptake (13% ID/g at 48 h). [123I]53 had the most favorable overall profile of the cumulative uptake over time of radiosensitive organs. Metabolite analysis of the four radiotracers found [123I]41 and [123I]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 [123I]53 displays favorable in vivo pharmacokinetics and stability and hence is an ideal candidate to proceed with further preclinical [131I] therapeutic evaluation. ©2015, American Chemical Societyen_AU
dc.identifier.citationRoberts, M. P., Nguyen, V., Ashford, M. E., Berghofer, P., Wyatt, N. A., Krause-Heuer, A. M., Pham, T. Q., Taylor, S. R., Hogan, L., Jiang, C. D., Fraser, B. H., Lengkeek, N. A., Matesic, L., Grégoire, M. C., Denoyer, D., Hocks, R. J., Katsifis, A., & Greguric. I. (2015). Synthesis and in vivo evaluation of [123I] melanin-targeted agents. Journal of Medicinal Chemistry, 58(15), 6214-6224. doi:10.1021/acs.jmedchem.5b00777en_AU
dc.identifier.govdoc8872en_AU
dc.identifier.issn0095-9065en_AU
dc.identifier.issue15en_AU
dc.identifier.journaltitleJournal of Medicinal Chemistryen_AU
dc.identifier.pagination6214-6224en_AU
dc.identifier.urihttps://doi.org/10.1021/acs.jmedchem.5b00777en_AU
dc.identifier.urihttp://apo.ansto.gov.au/dspace/handle/10238/9285en_AU
dc.identifier.volume58en_AU
dc.language.isoenen_AU
dc.publisherAmerican Chemical Societyen_AU
dc.subjectSynthesisen_AU
dc.subjectTracer techniquesen_AU
dc.subjectRadiopharmaceuticalsen_AU
dc.subjectTherapyen_AU
dc.subjectMelanomasen_AU
dc.subjectSingle photon emission computed tomographyen_AU
dc.subjectNeoplasmsen_AU
dc.subjectMelaninen_AU
dc.subjectAustraliaen_AU
dc.subjectIodine 123en_AU
dc.titleSynthesis and in vivo evaluation of [123I]melanin-targeted agentsen_AU
dc.typeJournal Articleen_AU
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