3 research outputs found
Effect of S4, doxorubicin, or the combination of both, on HT29 –CAIX high and HT29 –CAIX low tumor xenograft growth.
<p>Relative tumor volume (mean ± SEM) of HT29 –CAIX high (<b>A</b>) or HT29 –CAIX low xenografts (<b>B</b>) treated with vehicle (black), S4 (green), vehicle with doxorubicin (red), or S4 with doxorubicin (blue). Linear fits from relative tumor growth were used to estimate the mean time to reach 2 times start volume (T2XSV) of HT29 –CAIX high (<b>C</b>) or HT29 –CAIX low (<b>D</b>) xenografts.</p
Effect of S4 on doxorubicin sensitivity in MDA-MB-231 and FaDu cells.
<p>CAIX protein expression is higher during hypoxia in MDA-MB-231 and FaDu cells (<b>A</b>). Quantification of three independent biological repeats shows an almost twofold increase in CAIX expression (normalized to actin expression levels) in both cell lines (<b>B</b>). Cell viability assays of MDA-MB-231 (<b>C</b>) and FaDu cells (<b>D</b>) with increasing concentrations of doxorubicin. Cells were exposed to vehicle (black) or S4 (green) during normoxia (N), or to vehicle (red) or S4 (blue) during hypoxia (H). Results of three independent biological repeats are shown (mean ± SEM).</p
Synthesis and in Vivo Biological Evaluation of <sup>68</sup>Ga-Labeled Carbonic Anhydrase IX Targeting Small Molecules for Positron Emission Tomography
Tumor hypoxia contributes
resistance to chemo- and radiotherapy,
while oxygenated tumors are sensitive to these treatments. The indirect
detection of hypoxic tumors is possible by targeting carbonic anhydrase
IX (CA IX), an enzyme overexpressed in hypoxic tumors, with sulfonamide-based
imaging agents. In this study, we present the design and synthesis
of novel gallium-radiolabeled small-molecule sulfonamides targeting
CA IX. The compounds display favorable in vivo pharmacokinetics and
stability. We demonstrate that our lead compound, [<sup>68</sup>Ga]-<b>2</b>, discriminates CA IX-expressing tumors in vivo in a mouse
xenograft model using positron emission tomography (PET). This compound
shows specific tumor accumulation and low uptake in blood and clears
intact to the urine. These findings were reproduced in a second study
using PET/computed tomography. Small molecules investigated to date
utilizing <sup>68</sup>Ga for preclinical CA IX imaging are scarce,
and this is one of the first effective <sup>68</sup>Ga compounds reported
for PET imaging of CA IX