Synthesis and in Vivo Evaluation of [¹²³I]Melanin-Targeted Agents Academic Article uri icon


  • 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.


  • 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
  • Greguric, Ivan

publication date

  • 2015