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

Roberts, Maxine P., Nguyen, Vu, Ashford, Mark E., Berghofer, Paula, Wyatt, Naomi A., Krause-Heuer, Anwen M., Pham, Tien Q., Taylor, Stephen R., Hogan, Leena, Jiang, Cathy D., Fraser, Benjamin H., Lengkeek, Nigel A., Matesic, Lidia, Gregoire, Marie-Claude, Denoyer, Delphine, Hicks, Rodney J., Katsifis, Andrew and Greguric, Ivan 2015, Synthesis and in vivo evaluation of [123I]melanin-targeted agents, Journal of medicinal chemistry, vol. 58, no. 15, pp. 6214-6224, doi: 10.1021/acs.jmedchem.5b00777.

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Title Synthesis and in vivo evaluation of [123I]melanin-targeted agents
Author(s) Roberts, Maxine P.
Nguyen, Vu
Ashford, Mark E.
Berghofer, Paula
Wyatt, Naomi A.
Krause-Heuer, Anwen M.
Pham, Tien Q.
Taylor, Stephen R.
Hogan, Leena
Jiang, Cathy D.
Fraser, Benjamin H.
Lengkeek, Nigel A.
Matesic, Lidia
Gregoire, Marie-Claude
Denoyer, DelphineORCID iD for Denoyer, Delphine
Hicks, Rodney J.
Katsifis, Andrew
Greguric, Ivan
Journal name Journal of medicinal chemistry
Volume number 58
Issue number 15
Start page 6214
End page 6224
Total pages 11
Publisher American Chemical Society
Place of publication Washington, DC.
Publication date 2015-08-15
ISSN 0095-9065
Summary 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.
Language eng
DOI 10.1021/acs.jmedchem.5b00777
Field of Research 111207 Molecular Targets
111201 Cancer Cell Biology
0304 Medicinal And Biomolecular Chemistry
1115 Pharmacology And Pharmaceutical Sciences
0305 Organic Chemistry
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, American Chemical Society
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Document type: Journal Article
Collection: School of Life and Environmental Sciences
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