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Iodinated Choline Transport-Targeted Tracers.

Pavel Švec1,2, Zbyněk Nový3, Jan Kučka1

  • 1Institute of Macromolecular Chemistry, CAS, Heyrovského sq. 2, Prague 6 162 06, Czech Republic.

Journal of Medicinal Chemistry
|December 3, 2020
PubMed
Summary

We developed new radioiodinated tracers for imaging and therapy of choline transport diseases. These tracers offer advantages over current methods, including easier synthesis and superior performance in preclinical models.

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Area of Science:

  • Radiochemistry
  • Nuclear Medicine
  • Molecular Imaging

Background:

  • Pathological function of choline transport proteins is implicated in various diseases.
  • Current clinical imaging relies on short-lived positron emission tomography (PET) tracers like 11C or 18F labeled choline analogues.
  • There is a need for versatile tracers applicable in multiple imaging modalities and potentially therapy.

Purpose of the Study:

  • To develop novel radioiodinated tracers and theranostics targeting choline transport proteins.
  • To evaluate the potential of these compounds for diagnostic imaging and therapeutic applications.
  • To compare their performance against established choline tracers in preclinical models.

Main Methods:

  • Synthesis of a novel series of radioiodinated compounds.
  • In vitro characterization of ligand affinity and selectivity.
  • In vivo biodistribution studies using 125I-labeled compounds in prostate carcinoma (PC-3) xenograft mouse models.
  • Comparison with 18F-labeled fluorocholine.

Main Results:

  • Six compounds demonstrated nanomolar affinity for choline transport proteins.
  • The lead compound exhibited an affinity 100-fold greater than choline.
  • Two 125I-labeled compounds showed superior biodistribution profiles compared to [18F]fluorocholine in PC-3 mice.
  • Radioiodinated tracers are suitable for PET, SPECT, and potentially therapy.

Conclusions:

  • Novel radioiodinated tracers offer a promising alternative to existing choline analogues.
  • These compounds exhibit high affinity and favorable biodistribution for imaging choline transport.
  • The versatility of iodine isotopes allows for application in diagnostics and therapeutics, with simplified synthesis.