AT1R-Specific Ligand Angiotensin II as a Novel SPECT Agent for Hepatocellular Carcinoma Diagnosis
| Autor: | Zhaolun Li, Yi Ma, Ji Tao, Yueqing Gu, Fang Wang, Zicun Liu, Zhihao Han, Yuanbiao Tu, Changsheng Li, Peifei Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Carcinoma
Hepatocellular Bioengineering 02 engineering and technology Ligands 01 natural sciences Mice In vivo Cell Line Tumor Spect imaging medicine Animals Receptor Instrumentation Tomography Emission-Computed Single-Photon Fluid Flow and Transfer Processes Chemistry Angiotensin II Process Chemistry and Technology Liver Neoplasms 010401 analytical chemistry Cancer 021001 nanoscience & nanotechnology medicine.disease In vitro Rats 0104 chemical sciences Hepatocellular carcinoma Cancer research 0210 nano-technology Preclinical imaging |
| Zdroj: | ACS Sensors. 5:4072-4080 |
| ISSN: | 2379-3694 |
| Popis: | Hepatocellular carcinoma (HCC) is characterized by a high mortality and early diagnosis and treatment are critically needed. Ang II type 1 receptor (AT1R) has recently emerged as a potential molecular target for cancer diagnosis and intervention. Here, we labeled angiotensin II (Ang II), an AT1R ligand that is overexpressed in various solid cancers, with the near-infrared fluorescent dye, MPA, and radionuclide technetium-99m, and evaluated its capacity for HCC detection. These analyses were done in vitro using HepG2 (AT1R-positive) and BxPC3 (AT1R-negative) cell lines, and in vivo using a subcutaneous and orthotopic xenograft mouse model by fluorescence and SPECT imaging. Both Ang II-PEG4-MPA- and [99mTc]Tc-HYNIC-PEG4-Ang II-bound AT1R exhibited a high affinity in vitro and [99mTc]Tc-HYNIC-PEG4-Ang II displayed an acceptable level of in vitro stability in rat plasma and whole blood. In vivo imaging revealed excellent specific tumor-targeting in HepG2 mouse xenografts models. In vitro and in vivo competition experiments revealed specific Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II uptake by HepG2 cells and tumors. Altogether, AT1R-positive tumors were successfully detected via fluorescence and SPECT imaging using Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II, respectively. Given their superior targeting capacity, Ang II-PEG4-MPA and [99mTc]Tc-HYNIC-PEG4-Ang II are promising tools for HCC detection and warrant clinical translation. |
| Databáze: | OpenAIRE |
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