Synthesis and in vivo evaluation of [123I]melanin-targeted agents
Data(s) |
15/08/2015
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Resumo |
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. |
Identificador | |
Idioma(s) |
eng |
Publicador |
American Chemical Society |
Relação |
http://dro.deakin.edu.au/eserv/DU:30078002/denoyer-synthesisand-2015.pdf http://www.dx.doi.org/10.1021/acs.jmedchem.5b00777 http://www.ncbi.nlm.nih.gov/pubmed/26177000 |
Direitos |
2015, American Chemical Society |
Tipo |
Journal Article |