The Use of a Non-Conventional Long-Lived Gallium Radioisotope ⁶⁶Ga Improves Imaging Contrast of EGFR Expression in Malignant Tumours Using DFO-ZEGFR:2377 Affibody Molecule

• Main Authors: Maryam Oroujeni (Author), Tianqi Xu (Author), Katherine Gagnon (Author), Sara S. Rinne (Author), Jan Weis (Author), Javad Garousi (Author), Ken G. Andersson (Author), John Löfblom (Author), Anna Orlova (Author), Vladimir Tolmachev (Author)
• Format: Book
• Published: MDPI AG, 2021-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 of ⁶⁸Ga (67.6 min). Here, we therefore tested the hypothesis that the use of the non-conventional long-lived positron emitter ⁶⁶Ga (T_1/2 = 9.49 h, β⁺ = 56.5%) would permit imaging with higher contrast. ⁶⁶Ga was produced by the ⁶⁶Zn(p,n)⁶⁶Ga nuclear reaction and DFO-ZEGFR:2377 was efficiently labelled with ⁶⁶Ga 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 emitter ⁶⁶Ga for labelling of DFO-ZEGFR:2377 permits PET imaging of EGFR expression at 24 h after injection and improves imaging contrast.

Item Description

10.3390/pharmaceutics13020292
1999-4923