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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.
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Related Experiment Video

Updated: Jul 18, 2025

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[99mTc]Tc-PentixaTec: development, extensive pre-clinical evaluation, and first human experience.

Matthias Konrad1, Andreas Rinscheid2, Georgine Wienand3

  • 1Chair for Pharmaceutical Radiochemistry, Faculties of Chemistry and Medicine, Technische Universität München, 85748, Garching, Germany.

European Journal of Nuclear Medicine and Molecular Imaging
|August 19, 2023
PubMed
Summary

Researchers developed [99mTc]Tc-PentixaTec, a novel SPECT imaging agent targeting CXCR4. This agent shows high affinity, efficient internalization, and favorable dosimetry, making it promising for clinical use in hematologic malignancies.

Keywords:
CXCR4 imagingCancerPentapeptide tracerPlanar imagingSPECT/CT[99mTc]Tc-PentixaTec

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Area of Science:

  • Nuclear Medicine
  • Radiochemistry
  • Oncology

Background:

  • CXCR4 expression is crucial in hematologic malignancies.
  • Non-invasive imaging of CXCR4 is clinically valuable.
  • Existing PET agents like [68Ga]Ga-PentixaFor are effective but costly.

Purpose of the Study:

  • To develop and evaluate novel 99mTc-labeled cyclic pentapeptides for SPECT imaging of CXCR4.
  • To optimize labeling strategies and linker structures for improved affinity and targeting.
  • To assess the preclinical and early clinical performance of a lead candidate, [99mTc]Tc-PentixaTec.

Main Methods:

  • Synthesis of six mas3-conjugated CPCR4 analogs with varying linkers.
  • Radiolabeling with 99mTc using mas3, HYNIC, and N4 strategies.
  • In vitro binding and internalization studies using cancer cell lines.
  • In vivo biodistribution and SPECT/CT imaging in mice.
  • Early human SPECT/planar imaging and dosimetry in patients with hematologic malignancies.

Main Results:

  • N4-L6-CPCR4 demonstrated the highest affinity (0.6 ± 0.1 nM) and efficient internalization (97% at 2h).
  • [99mTc]Tc-N4-L6-CPCR4 ([99mTc]Tc-PentixaTec) showed high tumor uptake (8.6 ± 1.3% iD/g at 1h p.i.).
  • Human studies confirmed good tolerability, favorable biodistribution, dosimetry (2.1-3.4 mSv), and excellent tumor-to-background ratios.

Conclusions:

  • [99mTc]Tc-PentixaTec is a highly promising CXCR4-targeted SPECT agent.
  • Optimization of linker and labeling strategies yielded a superior radiotracer.
  • The agent exhibits excellent preclinical and clinical characteristics for diagnosing and monitoring CXCR4-expressing malignancies.