Title: Development and biological evaluation of ⁹⁹mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers
Authors: Akurathi, Vamsidhar ×
Dubois, Ludwig
Celen, Sofie
Lieuwes, Natasja G
Chitneni, Satish K
Cleynhens, Bernard J
Innocenti, Alessio
Supuran, Claudiu T
Verbruggen, Alfons M
Lambin, Philippe
Bormans, Guy M #
Issue Date: Jan-2014
Series Title: European Journal of Medicinal Chemistry vol:71 pages:374-84
Article number: 10.1016/j.ejmech.2013.10.027
Abstract: 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 (MAG2) tetradendate ligands and the conjugates radiolabelled with (99m)Tc, to obtain anionic and neutral (99m)Tc-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 MAG2 and labeled with (99m)Tc, 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 <0.5% ID/g at 0.5 h p.i for all the tracers. In vivo radiometabolite analysis indicated that at 1 h p.i. MAG₂ tetradendate ligands were more stable in plasma (>50% intact) compared to the neutral complex (28% intact). This preliminary data suggest that negatively charged (99m)Tc-labeled sulfonamide derivatives with modest lipophilicity and longer circulation time could be promising markers to target CA IX.
ISSN: 0223-5234
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Radiopharmacy
Laboratory of Molecular Bacteriology (Rega Institute)
× corresponding author
# (joint) last author

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