Preoperative Examination and Intraoperative Identification of Hepatocellular Carcinoma Using a Targeted Bimodal Imaging Probe

In dinical imaging modalities, MRI is suitable for preoperative examination. Fluorescence imaging has been proposed to improve the detectability of cancer lesions during the operation. However, the specificity and accuracy of the two imaging modalities is limited. To improve the prognosis and survival rate of the patient suffering from hepatocellular carcinoma (HCC), it is very important to develop a specific probe to achieve early detection and precise resection of HCC. We selected HCC targeting peptide SP94 to conjugate with a NIR dye and Gd chelated DOTA to enhance the specificity of different imaging modalities. MRI and fluorescence imaging were used for preoperative examination of the cancer and detecting the tumor in the operation, respectively. MRI and fluorescence signals significantly increased when HCC occurs and the obtained probe shows high uptake in HCC but negligible uptake in the normal liver tissues. The signal-to-background ratio is higher than 2.23 (MRI) and 2.0 (fluorescence imaging) with noninvasive imaging modalities. After the intraperitoneal cavity was surgically exposed, the signal-to-background ratio is higher than 4.6. By combining the high specificity of our probe with the high sensitivity of fluorescence imaging, the microprimary malignancy and micrometastasis foci (diameter <1 mm) can be easily detected after the intraperitoneal cavity is exposed. These results indicated that our probe is conductive to the early detection and precise resection of the HCC and has the potential to improve the diagnosis and treatment of patients with HCC.