Development and biological evaluation of Tc-99m-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers

Vamsidhar Akurathi, Ludwig Dubois, Sofie Celen, Natasja G. Lieuwes, Satish K. Chitneni, Bernard J. Cleynhens, Alessio Innocenti, Claudiu T. Supuran, Alfons M. Verbruggen, Philippe Lambin, Guy M. Bormans*

*Corresponding author for this work

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In vivo visualization of tumor hypoxia related markers, such as the endogenous transmembrane protein CA IX may lead to novel therapeutic and diagnostic applications in the management of solid tumors. In this study 4-(2-aminoethyl)benzene sulfonamide (AEBS, K-i = 33 nM for CA IX) has been conjugated with bis(aminoethanethiol) (BAT) and mercaptoacetyldiglycine (MAG(2)) tetradendate ligands and the conjugates radiolabelled with Tc-99m, to obtain anionic and neutral Tc-99m-labeled sulfonamide derivatives, respectively. The corresponding rhenium analogues were also prepared and showed good inhibitory activities against hCA IX (K-i = 59-66 nM). In addition, a second generation bis AEBS was conjugated with MAG(2) and labeled with Tc-99m, and the obtained diastereomers were also evaluated in targeting CA IX. Biodistribution studies in mice bearing HT-29 colorectal xenografts revealed a maximum tumor uptake of 50% intact) compared to the neutral complex (28% intact). This preliminary data suggest that negatively charged Tc-99m-labeled sulfonamide derivatives with modest lipophilicity and longer circulation time could be promising markers to target CA IX.
Original languageEnglish
Pages (from-to)374-384
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Jan 2014


  • Carbonic anhydrases
  • Sulfonamides
  • Technetium-99m
  • Rhenium
  • Biodistribution

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