Synthesis of a novel 99mTc labeled GE11 peptide for EGFR SPECT imaging

Int J Radiat Biol. 2020 Nov;96(11):1443-1451. doi: 10.1080/09553002.2020.1811419. Epub 2020 Sep 1.

Abstract

Purpose: This study investigated a novel SPECT agent for the noninvasive imaging of EGFR-overexpressing tumors.

Methods: The EGFR-targeting peptide GE11 was synthesized with the introduction of four amino acids (GGGC) to its C-terminal to act as a strong chelator and radiolabeled using 99mTc. The radiochemical yield of the 99mTc-peptide-GE11 were evaluated using RP-HPLC. Cellular assays of the probe were performed on two NSCLC cell lines: A549 (high expression) and H23 (low expression). Biodistribution and SPECT imaging were performed in BALB/c nude mice bearing A549 and H23 NSCLC xenografts.

Results: The 99mTc-peptide-GE11 was prepared at high efficiency with radiochemical yield of 98.40 ± 1.00 % and it showed favorable stability. The cellular uptake was significantly higher in A549 than in H23 at all time points (especially at 1 h, which was 10.34 ± 0.72 and 2.04 ± 0.18, respectively). A nearly 56% reduction in probe uptake was observed after pretreatment with excess unlabeled peptides. The performance of SPECT imaging and biodistribution demonstrated higher uptake of the 99mTc-peptide-GE11 in A549 xenograft than in H23 xenografts.

Conclusion: The new SPECT tracer 99mTc-peptide-GE11 showed EGFR specificity, favorable pharmacokinetics and great potential for EGFR-targeted imaging.

Keywords: 99mTc-labeled peptide conjugates; EGFR; NSCLC; SPECT; radionuclide imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Biological Transport
  • Chemistry Techniques, Synthetic
  • Drug Stability
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Isotope Labeling
  • Mice
  • Mice, Inbred BALB C
  • Peptides / chemical synthesis*
  • Peptides / chemistry*
  • Peptides / metabolism
  • Technetium / chemistry*
  • Tomography, Emission-Computed, Single-Photon*

Substances

  • GE11 peptide
  • Peptides
  • Technetium
  • ErbB Receptors