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Title: Synthesis and in vivo evaluation of [123I]melanin-targeted agents
Authors: Roberts, MP
Nguyen, VN
Ashford, ME
Berghofer, PJ
Wyatt, NA
Krause-Heuer, AM
Pham, TQ
Taylor, SR
Hogan, L
Jiang, CD
Fraser, BH
Lengkeek, NA
Matesic, L
Gregoire, MC
Denoyer, D
Hicks, RJ
Katsifis, A
Greguric, I
Keywords: Synthesis
Tracer techniques
Single photon emission computed tomography
Iodine 123
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
Gov't Doc #: 8872
ISSN: 0095-9065
Appears in Collections:Journal Articles

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