Improved tumor-to-organ ratios of a novel 67Ga-human epidermal growth factor radionuclide conjugate with preadministered antiepidermal growth factor receptor affibody molecules

Karl Sandström, Anna Karin Haylock, Irina Velikyan, Diana Spiegelberg, Heewa Kareem, Vladimir Tolmachev, Hans Lundqvist, Marika Nestor

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The overexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis. Targeted nuclear imaging of the EGFR expression could improve the diagnostics in patients with HNSCC. However, the high expression of EGFR in normal organs may conceal the tumor uptake and therefore limit the use. This study assesses the biodistribution of a novel human epidermal growth factor (hEGF) radionuclide conjugate after preinjection with anti-EGFR affibody molecules. hEGF was conjugated with p-SCN-Bn-NOTA and labeled with 67Ga. The biodistribution of [ 67Ga]Ga-NOTA-Bn-NCS-hEGF in nude mice with EGFR-expressing xenografts was evaluated either alone or 45 minutes after preinjection with one of the anti-EGFR affibody molecules Z EGFR:1907, (Z EGFR:1907) 2, or (Z EGFR:955) 2. The novel radioimmunoconjugate, [ 67Ga]Ga-NOTA-Bn-NCS-hEGF, demonstrated high stability in vitro and specific binding to hEGF in vitro and in vivo. Preinjection with anti-EGFR affibody molecules improved the tumor-to-organ ratio in the liver, salivary glands, and colon. Overall, the dimeric high-affinity affibody molecule (Z EGFR:1907) 2 exhibited the best results. These findings show that preblocking with an anti-EGFR affibody molecule is a promising tool that could improve the outcome of radionuclide-based imaging of EGFR-expressing tumors.

Original languageEnglish
Pages (from-to)593-601
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Volume26
Issue number5
DOIs
Publication statusPublished - 1 Oct 2011
Externally publishedYes

Keywords

  • affibody molecule
  • EGFR
  • gallium
  • head and neck cancer
  • molecular imaging
  • tumor-to-organ ratio

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'Improved tumor-to-organ ratios of a novel <sup>67</sup>Ga-human epidermal growth factor radionuclide conjugate with preadministered antiepidermal growth factor receptor affibody molecules'. Together they form a unique fingerprint.

Cite this