PET Imaging of Hepatocellular Carcinoma Using ZD2-(⁶⁸Ga-NOTA)

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Hepatocellular carcinoma (HCC) remains a significant global health challenge.
• Accurate diagnostic tools are crucial for effective HCC management.
• Targeting tumor-specific biomarkers in the microenvironment offers a promising avenue for imaging.

Purpose of the Study:

• To evaluate a novel short peptide radioligand for Positron Emission Tomography (PET) imaging of HCC.
• To assess the targeting capability of the radioligand against extra-domain B fibronectin (EDB-FN), an oncoprotein in the tumor microenvironment.
• To validate the utility of this radioligand in a relevant preclinical model of naturally occurring HCC.

Main Methods:

• A short linear peptide ZD2, conjugated with a ⁶⁸Ga-NOTA chelator, was developed as a radioligand.
• Dynamic PET imaging was performed in a woodchuck model of HCC after intravenous injection of the radioligand.
• Tissue samples were collected post-imaging for histological, PCR, and Western blot validation of EDB-FN expression and radioligand binding.

Main Results:

• The ZD2 radioligand demonstrated specific accumulation in HCC liver tumors.
• Radioligand uptake in tumors reached a plateau within minutes post-injection.
• Liver background uptake stabilized by 20 minutes, indicating favorable imaging kinetics.
• EDB-FN expression in woodchuck HCC was confirmed, validating the target.

Conclusions:

• The ZD2 short peptide radioligand is viable for PET imaging of HCC by targeting EDB-FN.
• This approach shows potential for improving the clinical diagnosis and management of HCC patients.
• Further development could lead to enhanced diagnostic capabilities for liver cancer.