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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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Visualizing Galectin-3 Binding Protein Expression with ImmunoPET.

Outi Keinänen1,2,3, Samantha M Sarrett1,3,4, Samantha Delaney1,3,4

  • 1Department of Chemistry, Hunter College, City University of New York, New York 10021, New York, United States.

Molecular Pharmaceutics
|May 16, 2023
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Summary

New radioimmunoconjugates targeting Galectin-3 binding protein (Gal-3BP) show promise for imaging and theranostics in various cancers. These novel immunoPET probes effectively visualize Gal-3BP-secreting tumors in preclinical models.

Keywords:
Zr-89antibody-drug conjugategalectin-3 binding proteinimmunoPETpositron emission tomographytheranostic imaging

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Area of Science:

  • Nuclear Medicine
  • Oncology
  • Radiopharmaceutical Chemistry

Background:

  • Galectin-3 binding protein (Gal-3BP) is overexpressed in multiple cancers, serving as a marker for tumor progression and poor prognosis.
  • Gal-3BP's expression across various neoplasms makes it a viable target for diagnostic and therapeutic strategies, including immuno-positron emission tomography (immunoPET) and antibody-drug conjugates (ADCs).

Purpose of the Study:

  • To develop and evaluate Galectin-3 binding protein-targeting radioimmunoconjugates for 89Zr-immunoPET imaging.
  • To assess the diagnostic potential of these novel probes in preclinical cancer models.

Main Methods:

  • Development of DFO-conjugated anti-Gal-3BP antibody (1959) and ADC (1959-sss/DM4).
  • Radiolabeling with Zirconium-89 (89Zr) to create [89Zr]Zr-DFO-1959 and [89Zr]Zr-DFO-1959-sss/DM4.
  • In vitro characterization, including binding affinity and serum stability.
  • In vivo evaluation using mice xenografts models (A375-MA1 and melanoma patient-derived xenografts).

Main Results:

  • Both radioimmunoconjugates demonstrated high affinity for Gal-3BP and excellent stability in human serum (>80% intact after 168 hours).
  • [89Zr]Zr-DFO-1959 effectively delineated Gal-3BP-secreting tumors in vivo, showing high tumoral uptake (54.8 ± 15.8%ID/g) and tumor-to-background ratios (8.0 ± 4.6) at 120 hours.
  • Both probes visualized Gal-3BP-expressing tumors in murine models, with comparable pharmacokinetic profiles, although the ADC conjugate showed higher spleen and kidney uptake.

Conclusions:

  • The developed 89Zr-labeled radioimmunoconjugates, [89Zr]Zr-DFO-1959 and [89Zr]Zr-DFO-1959-sss/DM4, are effective in visualizing Gal-3BP-secreting tumors in preclinical settings.
  • These probes hold significant potential for clinical immunoPET imaging of Gal-3BP-expressing malignancies.
  • They may serve as companion theranostics to identify patients suitable for Gal-3BP-targeted therapies, such as the 1959-sss/DM4 ADC.