Synthesis and evaluation of indium-111-labeled imidazothiadiazole sulfonamide derivative for single photon emission computed tomography imaging targeting carbonic anhydrase-IX

[Display omitted] •An 111In-labeled imidazothiadiazole sulfonamide ([111In]DO3A-IS1) was synthesized.•[111In]DO3A-IS1 exhibited selective binding to CA-IX high-expressing cells.•[111In]DO3A-IS1 showed marked accumulation in CA-IX high-expressing tumors.•[111In]DO3A-IS1 indicated rapid clearance from the blood and muscle in vivo.•[111In]DO3A-IS1 facilitated clear tumor imaging with SPECT. Carbonic anhydrase-IX (CA-IX) is a zinc enzyme overexpressed in the hypoxic regions of many types of solid tumors; therefore, in vivo imaging of CA-IX may contribute to cancer diagnosis. In this study, we newly designed and synthesized an 111In-labeled CA-IX imaging agent based on an imidazothiadiazole sulfonamide (IS) scaffold conjugated with a chelating moiety, DO3A ([111In]DO3A-IS1), and evaluated its utility for imaging of CA-IX high-expressing tumors. [111In]DO3A-IS1 was successfully synthesized at a 76% radiochemical yield by reacting its precursor with 111InCl3 in acetate buffer. In in vitro assays, [111In]DO3A-IS1 showed marked stability in murine plasma and greater binding to CA-IX high-expressing (HT-29) cells (118 ± 21% initial dose/mg protein) than CA-IX low-expressing (MDA-MB-231) cells (1.4 ± 0.3% initial dose/mg protein). Moreover, in an in vivo biodistribution assay, [111In]DO3A-IS1 showed marked accumulation in the HT-29 tumor (8.71 ± 1.41% injected dose/g at 24 h postinjection). In addition, in a single photon emission computed tomography (SPECT) study, [111In]DO3A-IS1 clearly and selectively visualized the HT-29 tumor as compared with the MDA-MB-231 tumor. These results indicate that [111In]DO3A-IS1 may serve as a useful SPECT imaging agent with the novel scaffold targeting CA-IX.