ACS Appl Mater & Interfaces----Magnetic resonance/optical multimodal probes for microscopic primary liver tumors
ACS Applied Materials & Interfaces recently reported the joint research results of the Fudan University School of Pharmacy and the Second Affiliated Hospital of Zhejiang University School of Medicine: Multimodality Exploration for Navigation of Minimal Primary Liver Tumor Surgery needle. The probe can not only locate micro-primary liver tumors (diameter 1-4 mm) by magnetic resonance imaging (MRI) before surgery, but also guide the resection of small micro-tumors by near-infrared fluorescence imaging during surgery. This achievement is expected to achieve early detection and prognosis of primary liver tumors.
Figure 1. Target probes achieve high signal-to-noise ratio tracing of tumors by targeting tumor marginal neovascular endothelial cells and tumor cells with high expression of the Endoglin receptor.。
Primary liver cancer is currently the second leading cause of cancer-related death, and surgical resection is the primary means of treatment for primary liver cancer. Patients with early surgery can achieve a 5-year survival rate of up to 70% after timely resection or transplantation, but only for palliative treatment of advanced liver cancer patients with a median survival of less than 1 year. However, early detection of primary liver cancer is a huge challenge. For small primary liver cancers less than 1.0 cm in diameter, the diagnostic sensitivity of computed tomography (CT) is usually as low as 10-33%, and the diagnostic sensitivity of MRI is as low as 29-43%. Even with enhanced contrast agents, the diagnostic rate of micro-primary liver cancer is still low due to the lack of tumor targeting specificity. Considering the significant improvement in the prognosis of patients with early-stage liver tumors, accurate diagnosis of primary liver cancer less than 1.0 cm in diameter is essential for improving efficacy.
Figure 2. H&E staining and immunofluorescence staining of the patient's primary liver cancer tissue sections showed that the expression level of the Endoglin receptor at the tumor border was significantly higher than that of the tumor center and surrounding normal liver tissue.
Figure 3. Immunofluorescence sections confirm that the probe (red) is clustered in the marginal region of the primary liver tumor model. Colocalization with the endoglin receptor (green of B) confirms the targeting of the probe
Dr. Yan Yan, MD, attending physician of the Second Affiliated Hospital of Zhejiang University School of Medicine, Gao Xihui, Ph.D., and Ph.D. student of Fudan University School of Medicine, Zhang Yunfei, the first author of the paper, Dr. Yan Yan, Professor Li Cong and the Second Affiliated Hospital of Zhejiang University Medical College Du Qin, the chief physician of internal medicine, is the co-author of the paper. Professor Li Cong believes that this is the first multimodal imaging probe to detect micro-primary liver cancer using aptamers as targeting groups. It is expected to achieve high signal-to-noise ratio tracing of preoperative and intraoperative micro primary liver tumors after one injection. The real-time comparison between the pre-operative positioning image and the in-operative navigation image can also avoid the distortion of the navigation signal caused by the liver displacement during the operation, and further improve the surgical prognosis.
Title：Imaging Tiny Hepatic Tumor Xenografts via Endoglin-Targeted Paramagnetic/Optical Nanoprobe. DOI:10.1021/acsami.8b02648
https://pubs.acs.org/doi/full/10.1021/acsami.8b02648
Abstract: Surgery is the mainstay for treating hepatocellular carcinoma (HCC). However, it is a great challenge for surgeons to identify HCC in its early developmental stage. The diagnostic sensitivity for a tiny HCC with a diameter less than 1.0 cm is usually as low as 10-33% for computed tomography (CT) and 29-43% for magnetic resonance imaging (MRI). Although MRI is the preferred imaging modality for detecting HCC, with its unparalleled spatial resolution for soft tissue, the commercially available contrast agent, such as Gd3+-DTPA, cannot accurately define HCC because of its short circulation lifetime and lack of tumor-targeting specificity. Endoglin (CD105), a type I membrane glycoprotein, is highly expressed both in HCC cells and in the endothelial cells of neovasculature, which are abundant at the tumor periphery. In this work, a novel single-stranded DNA oligonucleotide-based aptamer was screened by systematic evolution of ligands in an exponential enrichment assay and showed a high binding affinity (KD = 98 pmol/L) to endoglin. Conjugating the aptamers and imaging reporters on a G5 dendrimer created an HCC-targeting nanoprobe that allowed the successful visualization of orthotopic HCC xenografts with diameters as small as 1?4 mm. Significantly, the invasive tumor margin was clearly delineated, with a tumor to normal ratio of 2.7 by near-infrared (NIR) fluorescence imaging and 2.1 by T1-weighted MRI. This multimodal nanoprobe holds promise not only for noninvasively defining tiny HCC by preoperative MRI but also for guiding tumor excision via intraoperative NIR fluorescence imaging, which will probably gain benefit for the patient’s therapeutic response and improve the survival rate.
