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Synthesis and Preclinical Evaluation of Dual-Specific Probe Targeting Glypican-3 and Prostate-Specific Membrane Antigen for Hepatocellular Carcinoma PET Imaging

  • 0Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
Molecular Pharmaceutics +

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December 10, 2024

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December 10, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

A novel dual-specific probe, T2P, targeting Glypican-3 (GPC3) and prostate-specific membrane antigen (PSMA), shows enhanced positron emission tomography (PET) imaging for hepatocellular carcinoma (HCC). Radiolabeled T2P demonstrated superior tumor uptake and retention compared to its individual targeting components.

Area Of Science

  • Nuclear Medicine
  • Oncology
  • Radiopharmaceutical Chemistry

Background

  • Hepatocellular carcinoma (HCC) diagnosis and staging benefit from advanced imaging techniques like positron emission tomography (PET).
  • Targeting specific biomarkers such as Glypican-3 (GPC3) and prostate-specific membrane antigen (PSMA) can improve PET imaging accuracy for HCC.

Purpose Of The Study

  • To evaluate a novel dual-specific probe (T2P) for PET imaging of HCC by simultaneously targeting GPC3 and PSMA.
  • To assess the performance of T2P labeled with gallium-68 ([sup:68Ga]Ga-T2P) and fluorine-18 ([sup:18F]AlF-T2P) in preclinical HCC models.

Main Methods

  • A dual-specific probe T2P was synthesized by conjugating a GPC3-targeting peptide (TJ12P2) to a PSMA inhibitor via a polyethylene glycol linker and a NOTA chelator.
  • T2P was radiolabeled with [sup:68Ga] and [sup:18F]AlF and evaluated in murine HCC models with varying GPC3 and PSMA expression levels.
  • PET imaging, blocking studies, and in vitro cell assays were performed to confirm targeting specificity, affinity, and in vivo performance.

Main Results

  • Both [sup:68Ga]Ga-T2P and [sup:18F]AlF-T2P demonstrated high stability and specific binding to GPC3 and PSMA targets.
  • [sup:68Ga]Ga-T2P showed significantly higher uptake in HCC tumors with high GPC3/PSMA expression compared to monomeric probes ([sup:68Ga]Ga-TJ12P2 or [sup:68Ga]Ga-PSMA-617).
  • [sup:18F]AlF-T2P exhibited superior tumor-to-muscle ratios compared to [sup:68Ga]Ga-T2P, and blocking studies confirmed the dual-targeting specificity of T2P.

Conclusions

  • The dual-specific radiolabeled probe T2P demonstrates enhanced tumor uptake and retention in HCC models compared to its individual targeting components.
  • PET imaging with [sup:68Ga]Ga-T2P and [sup:18F]AlF-T2P offers comparable imaging quality, suggesting T2P is a promising tool for HCC diagnosis.

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