Preclinical Evaluation of CD36-Targeting Antiangiogenic Peptide ABT-510 for Near-Infrared Fluorescence Molecular Imaging of Colorectal Cancer.

Surgical resection constitutes the first choice of treatment for colorectal cancer (CRC). Despite advancements in intraoperative navigation, there remains a considerable lack of effective targeting probes for the imaging-guided surgical navigation of CRC owing to their high heterogeneity. Hence, developing a suitable fluorescent probe to detect the specific types of CRC populations is crucial. Herein, we labeled ABT-510, a small, CD36-targeting thrombospondin-1-mimetic peptide overexpressed in various cancer types, with fluorescein isothiocyanate or near-infrared dye MPA. We found that fluorescence-conjugated ABT-510 exhibited excellent selectivity and specificity toward cells or tissues with high CD36 expression. The tumor-to-colorectal signal ratios were 11.28 ± 0.61 (95% confidence interval) and 10.74 ± 0.07 (95% confidence interval) in subcutaneous HCT-116 and HT-29 tumor-bearing nude mice, respectively. Moreover, high signal contrast was observed in the orthotopic and liver metastatic CRC xenograft mouse models. Furthermore, MPA-PEG4-r-ABT-510 exhibited an antiangiogenic effect via tube information assay with human umbilical vein endothelial cells. Overall, MPA-PEG4-r-ABT-510 presents rapid and precise tumor delineation characteristics, thereby making it a desirable tool for CRC imaging and surgical navigation.

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-PEG3-k-Icatibant and radioconjugate [99mTc]Tc-HYNIC-PEG4-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-PEG4-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.