The use of a non-conventional long-lived gallium radioisotope66Ga improves imaging contrast of EGFR expression in malignant tumours using dfo-zegfr:2377 affibody molecule

Maryam Oroujeni, Tianqi Xu, Katherine Gagnon, Sara S. Rinne, Jan Weis, Javad Garousi, Ken G. Andersson, John Löfblom, Anna Orlova, Vladimir Tolmachev

Research output: Contribution to journalArticlepeer-review

Abstract

Epidermal growth factor receptor (EGFR) is overexpressed in many malignancies. EGFR-targeted therapy extends survival of patients with disseminated cancers. Radionuclide molecular imaging of EGFR expression would make EGFR-directed treatment more personalized and therefore more efficient. A previous study demonstrated that affibody molecule [68Ga]Ga-DFO-ZEGFR:2377 permits specific positron-emission tomography (PET) imaging of EGFR expression in xenografts at 3 h after injection. We anticipated that imaging at 24 h after injection would provide higher contrast, but this is prevented by the short half-life of68Ga (67.6 min). Here, we therefore tested the hypothesis that the use of the non-conventional long-lived positron emitter66Ga (T1/2 = 9.49 h, β+ = 56.5%) would permit imaging with higher contrast.66Ga was produced by the66Zn(p,n)66Ga nuclear reaction and DFO-ZEGFR:2377 was efficiently labelled with66Ga with preserved binding specificity In Vitro and in vivo. At 24 h after injection, [66Ga]Ga-DFO-ZEGFR:2377 provided 3.9-fold higher tumor-to-blood ratio and 2.3-fold higher tumor-to-liver ratio than [68Ga]Ga-DFO-ZEGFR:2377 at 3 h after injection. At the same time point, [66Ga]Ga-DFO-ZEGFR:2377 provided 1.8-fold higher tumor-to-blood ratio, 3-fold higher tumor-to-liver ratio, 1.9-fold higher tumor-to-muscle ratio and 2.3-fold higher tumor-to-bone ratio than [89Zr]Zr-DFO-ZEGFR:2377. Biodistribution data were confirmed by whole body PET combined with magnetic resonance imaging (PET/MRI). The use of the positron emitter66Ga for labelling of DFO-ZEGFR:2377 permits PET imaging of EGFR expression at 24 h after injection and improves imaging contrast.

Original languageEnglish
Article number292
Pages (from-to)1-18
Number of pages18
JournalPharmaceutics
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 2021

Keywords

  • A431 xenograft
  • Affibody molecule
  • Epidermal growth factor receptor
  • Gallium-66
  • PET imaging
  • ZEGFR:2377

ASJC Scopus subject areas

  • Pharmaceutical Science

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