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Related Experiment Video

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Murine Lymphocyte Labeling by 64Cu-Antibody Receptor Targeting for In Vivo Cell Trafficking by PET/CT
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A Targeted Radiotheranostic Agent for Glioblastoma: [64Cu]Cu-NOTA-TP-c(RGDfK).

Alireza Mirzaei1, Samia Ait-Mohand1, Prenitha Mercy Ignatius Arokia Doss1

  • 1Department of Medical Imaging and Radiation Sciences, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.

Brain Sciences
|August 28, 2025
PubMed
Summary
This summary is machine-generated.

A novel radiotheranostic agent, [64Cu]Cu-NOTA-TP-c(RGDfK), shows promise for glioblastoma (GBM) treatment. This agent effectively targets GBM cells, exhibiting high cytotoxicity while sparing normal cells, indicating potential for improved GBM therapy.

Keywords:
copper-64glioblastoma multiforme (GBM)integrin αvβ3 targetingradiotheranosticsterpyridine-platinum complex

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Area of Science:

  • Oncology
  • Radiochemistry
  • Molecular Imaging

Background:

  • Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options.
  • Integrin αvβ3, overexpressed in GBM, is a key target for diagnostic and therapeutic strategies.
  • Radiotheranostic agents offer combined imaging and therapeutic benefits for targeted cancer treatment.

Purpose of the Study:

  • To develop and evaluate a novel radiotheranostic agent, [64Cu]Cu-NOTA-TP-c(RGDfK), for targeting glioblastoma (GBM).
  • To assess the binding affinity, cellular uptake, and cytotoxicity of the novel agent in GBM cells.

Main Methods:

  • Synthesis and radiolabeling of [64Cu]Cu-NOTA-TP-c(RGDfK) using copper-64 (64Cu).
  • Comparative cellular studies using U87 MG glioblastoma cells and SVG p12 astrocytes.
  • Evaluation of binding affinity, cellular uptake, internalization, retention, and cytotoxicity compared to control agents.

Main Results:

  • High radiochemical purity (>99%) and strong binding affinity (IC50 = 16 ± 8 nM) to integrin αvβ3 were achieved.
  • Significantly higher cellular uptake (38.8 ± 1.8%) and internalization (28.0 ± 1.0%) in U87 MG cells compared to controls.
  • Demonstrated potent cytotoxicity (IC50 = 10 ± 2 nM) in U87 MG cells with minimal toxicity in normal astrocytes.

Conclusions:

  • [64Cu]Cu-NOTA-TP-c(RGDfK) is a promising targeted radiotheranostic agent for glioblastoma.
  • The agent exhibits specific targeting, effective cellular uptake, and potent cytotoxicity against GBM cells.
  • Further preclinical development is warranted for this novel GBM therapeutic and diagnostic agent.