In vivo near-infrared fluorescence and SPECT-CT imaging of colorectal Cancer using the bradykinin B2R-specific ligand icatibant.

Cancer molecular imaging using specific probes designed to identify target proteins in cancer is a powerful tool to guide therapeutic selection, patient management, and follow-up. We demonstrated that icatibant may be used as a targeting probe for the significantly upregulated bradykinin B2R in colorectal cancer (CRC). Icatibant-based probes with high affinity towards bradykinin B2R were identified. The near-infrared (NIR) fluorescent dye conjugate MPA-PEG 3 -k-Icatibant and radioconjugate [99mTc]Tc-HYNIC-PEG 4 -Icatibant exhibited favourable selective and specific uptake in tumours when the subcutaneous and orthotopic colorectal tumour-bearing mouse models were imaged using NIR fluorescence imaging and Single-Photon Emission Computed Tomography–Computed Tomography (SPECT-CT), respectively. The tracer of [99mTc]Tc-HYNIC-PEG 4 -Icatibant accumulated in tumours according to biodistribution studies and peaked at 4 h with an uptake value of 3.41 ± 0.27%ID/g in HT29 tumour-bearing nude mice following intravenous injection (i.v.). The tumour-to-colorectal signal ratios were 5.03 ± 0.37, 15.45 ± 0.32, 13.58 ± 1.19 and 11.33 ± 1.73 1, 2, 4 and 6 h after tail-veil injection, respectively. Overall, in the wake of rapid and precise tumour delineation and penetration characteristics, icatibant-based probes represent promising high-contrast molecular imaging probes for the detection of bradykinin B2R. Icatibant, which is FDA-approved for hereditary angioedema (HAE) treatment, was labelled with a NIR dye MPA and radionuclide technetium-99 m. And we found that Icatibant-based probes exhibited high contrast over background signals and substantial tumour retention in subcutaneous and orthotopic colorectal cancer xenograft mouse models. [Display omitted] • Icatibant was found to target colorectal cancer. • Icatibant-based probes can detect in situ colorectal cancer with high tumour-to-background signal contrast. • Icatibant combined with radionuclides or potent cytotoxins should provide impetus in targeted therapies. [ABSTRACT FROM AUTHOR]