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Imaging EGFR and HER3 through 89Zr-labeled MEHD7945A (Duligotuzumab)

Brooke N McKnight1, Akhila N W Kuda-Wedagedara1, Kuntal K Sevak2

  • 1Department of Oncology, Karmanos Cancer Institute, 4100 John R. Street, Detroit, MI, 48201, USA.

Scientific Reports
|June 15, 2018
PubMed

Insights

A novel positron emission tomography (PET) imaging agent, 89Zr-MEHD7945A, was developed to visualize targets of the dual immunotherapy agent duligotuzumab (MEHD7945A) in pancreatic cancer. This tool aids in understanding drug distribution and target engagement.

Area of Science:

  • Oncology
  • Molecular Imaging
  • Pharmacology

Background:

  • Tumor resistance necessitates therapies targeting multiple molecular pathways.
  • Crosstalk between epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3) drives resistance.
  • EGFR and HER3 are key targets for novel cancer therapies.

Purpose of the Study:

  • To develop and evaluate a positron emission tomography (PET) companion diagnostic for MEHD7945A (duligotuzumab).
  • To assess the tumor uptake and whole-body pharmacokinetics of 89Zr-MEHD7945A in pancreatic cancer.
  • To examine the specificity of the PET probe for EGFR and HER3.

Main Methods:

  • Radiolabeling of MEHD7945A with Zirconium-89 (89Zr).
  • Preclinical evaluation in a pancreatic cancer model.
  • Positron emission tomography (PET) imaging to determine tumor accretion and biodistribution.
  • Pharmacokinetic analysis of 89Zr-MEHD7945A.

Main Results:

  • Successful development and characterization of the 89Zr-MEHD7945A PET imaging agent.
  • Demonstrated tumor uptake of 89Zr-MEHD7945A in pancreatic cancer.
  • Established whole-body pharmacokinetic profile of the imaging agent.
  • Preliminary assessment of probe specificity for EGFR and HER3.

Conclusions:

  • 89Zr-MEHD7945A serves as a promising PET companion diagnostic for MEHD7945A (duligotuzumab).
  • This imaging agent can visualize target engagement and drug distribution in pancreatic cancer.
  • Further studies are warranted to confirm specificity and clinical utility.

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