A Novel ^99mTc-Labeled Quinazoline-Based Isocyanide Probe for EGFR Imaging: Synthesis and Biological Evaluation

Area of Science:

• Nuclear medicine
• Radiopharmaceutical chemistry
• Oncology

Background:

• Epidermal growth factor receptor (EGFR) is a key target in many solid tumors.
• Current EGFR tyrosine kinase inhibitors (EGFR-TKIs) face limitations in efficacy and resistance development.
• Noninvasive methods for visualizing EGFR expression are needed for patient stratification.

Purpose of the Study:

• To develop and evaluate a novel ^99mTc-labeled quinazoline derivative as a SPECT imaging agent for EGFR.
• To assess the probe's potential for noninvasive visualization of EGFR expression in tumors.

Main Methods:

• Synthesis and characterization of a novel ^99mTc-labeled quinazoline derivative ([^99mTc][Tc-(CN-PEG₂-QZL)₆]⁺).
• In vitro cellular uptake studies in EGFR-overexpressing A431 cells.
• In vivo biodistribution and SPECT/CT imaging studies in A431 tumor-bearing mice.
• Blocking studies with EGFR inhibitors to confirm target specificity.

Main Results:

• The ^99mTc-labeled probe was prepared with high radiochemical purity and stability.
• Efficient cellular uptake and internalization were observed in EGFR-overexpressing cells.
• Tumor accumulation was confirmed in vivo, with reduced uptake upon co-administration of an EGFR inhibitor.
• SPECT/CT imaging successfully visualized EGFR-overexpressing tumors, demonstrating target specificity.

Conclusions:

• [^99mTc][Tc-(CN-PEG₂-QZL)₆]⁺ is a promising SPECT imaging agent for targeting EGFR.
• The tracer enables noninvasive visualization of EGFR expression, supporting patient stratification.
• Further optimization is needed to improve the pharmacokinetic profile, particularly reducing liver uptake.