Preclinical Evaluation of [68 Ga]Ga-DFO-ZEGFR:2377: A Promising Affibody-Based Probe for Noninvasive PET Imaging of EGFR Expression in Tumors

Cells
Maryam OroujeniVladimir Tolmachev

Abstract

Radionuclide imaging of epidermal growth factor receptor (EGFR) expression in tumors may stratify patients for EGFR-targeting therapies and predict response or resistance to certain treatments. Affibody molecules, which are nonimmunoglobulin scaffold proteins, have a high potential as probes for molecular imaging. In this study, maleimido derivative of desferrioxamine B (DFO) chelator was site-specifically coupled to the C-terminal cysteine of the anti-EGFR affibody molecule ZEGFR:2377, and the DFO-ZEGFR:2377 conjugate was labeled with the generator-produced positron-emitting radionuclide 68Ga. Stability, specificity of binding to EGFR-expressing cells, and processing of [68Ga]Ga-DFO-ZEGFR:2377 by cancer cells after binding were evaluated in vitro. In vivo studies were performed in nude mice bearing human EGFR-expressing A431 epidermoid cancer xenografts. The biodistribution of [68Ga]Ga-DFO-ZEGFR:2377 was directly compared with the biodistribution of [89Zr]Zr-DFO-ZEGFR:2377. 2377 was efficiently (isolated yield of 73 ± 3%) and stably labeled with 68Ga. Binding of [68Ga]Ga-DFO-ZEGFR:2377 to EGFR-expressing cells in vitro was receptor-specific and proportional to the EGFR expression level. In vivo saturation experiment demonstrat...Continue Reading

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Citations

Jul 15, 2020·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Marie BrandtThomas L Mindt
Mar 15, 2020·Cancers·Vladimir Tolmachev, Anna Orlova
Jun 25, 2020·EJNMMI Radiopharmacy and Chemistry·Javad GarousiVladimir Tolmachev
Oct 14, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Shahab Ranjbar BahadoriXiankai Sun
Feb 2, 2021·Applied Microbiology and Biotechnology·Mingyang LiShanli Zhu
May 1, 2021·International Journal of Molecular Sciences·Sara S RinneVladimir Tolmachev
Jul 25, 2021·International Journal of Molecular Sciences·Sona KrajcovicovaMilos Petrik

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Methods Mentioned

BETA
biopsy
imaging techniques
xenografts
xenograft

Software Mentioned

MultiGauge
Tera
GraphPad Prism
GraphPad
[UNK]
Nucline
OptiQuant

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