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|Title: ||Synthesis and in vivo evaluation of [123I]melanin-targeted agents|
|Authors: ||Roberts, MP|
Single photon emission computed tomography
|Issue Date: ||15-Aug-2015|
|Publisher: ||American Chemical Society|
|Citation: ||Roberts, 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., Gregoire, 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.5b00777|
|Abstract: ||This 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 Society|
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