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Related Concept Videos

Positron Emission Tomography01:29

Positron Emission Tomography

Positron emission tomography (PET) is a medical imaging technique involving radiopharmaceuticals — substances that emit short-lived radiation. Although the first PET scanner was introduced in 1961, it took 15 more years before radiopharmaceuticals were combined with the technique and revolutionized its potential.
One of the main requirements of a PET scan is a positron-emitting radioisotope, which is produced in a cyclotron and then attached to a substance used by the part of the body being...
Imaging Studies II: Positron Emission Tomography and Scintigraphy01:25

Imaging Studies II: Positron Emission Tomography and Scintigraphy

Positron Emission Tomography (PET) is a medical imaging technique that provides crucial insights into the body's physiological functions at a molecular level. It is an indispensable resource for diagnosing, staging, and monitoring various illnesses, notably cancer, neurological disorders, and cardiovascular conditions.
Fundamental Principles of PET

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Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging
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Development and In Vitro Evaluation of [64Cu]Cu-NOTA-TP-PSMA, a Novel Radiotheranostic Agent Against Prostate Cancer.

Hoda Talebian1, 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.

International Journal of Molecular Sciences
|December 11, 2025
PubMed
Summary

A new radiotheranostic agent, [64Cu]Cu-NOTA-TP-PSMA, shows promise for prostate cancer (PCa). It effectively targets PSMA-positive cancer cells with high uptake and potent cytotoxicity, offering a potential new tool for PCa diagnosis and treatment.

Keywords:
PSMAcopper-64in vitro validationprostate cancerradiotheranostic agentterpyridine-platinum

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Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
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Area of Science:

  • Nuclear medicine
  • Oncology
  • Radiopharmaceutical chemistry

Background:

  • Metastatic prostate cancer (PCa) presents significant clinical challenges due to limited diagnostic and therapeutic strategies.
  • Prostate-specific membrane antigen (PSMA) is a validated target for PCa theranostics.
  • Developing novel agents that combine diagnostic imaging and therapeutic capabilities is crucial.

Purpose of the Study:

  • To develop and evaluate a novel radiotheranostic agent, [64Cu]Cu-NOTA-TP-PSMA, for prostate cancer.
  • To compare the biological performance of [64Cu]Cu-NOTA-TP-PSMA with its monomeric analogs.
  • To assess the in vitro efficacy and selectivity of the novel agent.

Main Methods:

  • Synthesis of [64Cu]Cu-NOTA-TP-PSMA by conjugating a PSMA ligand to a 64Cu-radiolabeled terpyridine-platinum (TP) compound.
  • In vitro studies using PSMA-positive LNCaP prostate cancer cells and non-malignant HEK-293 cells.
  • Evaluation of agent stability, PSMA binding affinity, cellular uptake, internalization, retention, nuclear localization, cytotoxicity, and toxicity.

Main Results:

  • [64Cu]Cu-NOTA-TP-PSMA demonstrated high stability and strong PSMA binding affinity.
  • The agent exhibited significantly enhanced uptake, internalization, retention, and nuclear localization in LNCaP cells compared to monomeric analogs.
  • Potent and selective cytotoxicity was observed in LNCaP cells (EC50 in low nanomolar range) with negligible toxicity in HEK-293 cells.

Conclusions:

  • [64Cu]Cu-NOTA-TP-PSMA is a highly promising radiotheranostic agent for prostate cancer.
  • The agent displays superior in vitro performance, including enhanced tumor cell targeting and potent selective cytotoxicity.
  • Further in vivo evaluation is warranted for potential clinical applications in prostate cancer imaging and targeted radiotherapy.