CD24 as a Novel Radiopharmaceutical Target for Hepatocellular Carcinoma.

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Hepatocellular carcinoma (HCC) poses a significant global mortality challenge.
• Differentiating viable HCC from nonviable tissue post-treatment is difficult with current imaging.
• CD24, a protein overexpressed in HCC, presents a potential imaging target.

Purpose of the Study:

• To develop and evaluate a CD24-targeted antibody-based positron emission tomography (immuno-PET) tracer for noninvasive HCC detection.
• To assess the specificity and efficacy of the novel tracer in preclinical models.

Main Methods:

• Assessed CD24 expression in HCC cell lines using qPCR, Western blot, and flow cytometry.
• Generated CD24-negative cell lines via CRISPR/Cas9 gene editing for control studies.
• Synthesized and characterized the [89Zr]Zr-DFO-α-hCD24 immuno-PET tracer.
• Evaluated tracer uptake in vivo using PET/CT imaging and ex vivo biodistribution in xenograft models.

Main Results:

• High CD24 expression confirmed in multiple HCC cell lines.
• The anti-CD24 antibody demonstrated strong binding affinity for CD24.
• The [89Zr]Zr-DFO-α-hCD24 tracer was produced with high radiochemical yield and purity.
• Specific and significant uptake of the tracer was observed in CD24-positive HCC tumors compared to CD24-negative tumors.

Conclusions:

• CD24 is a promising target for hepatocellular carcinoma radiotheranostics.
• The developed [89Zr]Zr-DFO-α-hCD24 immuno-PET tracer shows potential for noninvasive HCC detection.
• Further optimization is needed to enhance tumor-to-liver signal for improved clinical application and radiopharmaceutical therapy.