Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jul 20;7(1):5961.
doi: 10.1038/s41598-017-05700-7.

The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

Javad Garousi  1 , Ken G Andersson  2 , Johan H Dam  3 , Birgitte B Olsen  3 , Bogdan Mitran  4 , Anna Orlova  4 , Jos Buijs  1 , Stefan Ståhl  2 , John Löfblom  2 , Helge Thisgaard  3 , Vladimir Tolmachev  5
Affiliations

The use of radiocobalt as a label improves imaging of EGFR using DOTA-conjugated Affibody molecule

Javad Garousi et al. Sci Rep. .

Abstract

Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The 111In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377. DOTA-ZEGFR:2377 was labelled with 57Co (T1/2 = 271.8 d), 55Co (T1/2 = 17.5 h), and, for comparison, with the positron-emitting radionuclide 68Ga (T1/2 = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope 57Co was used in animal studies. Both 57Co-DOTA-ZEGFR:2377 and 68Ga-DOTA-ZEGFR:2377 demonstrated EGFR-specific accumulation in A431 xenografts and EGFR-expressing tissues in mice. Tumour-to-organ ratios for the radiocobalt-labelled DOTA-ZEGFR:2377 were significantly higher than for the gallium-labelled counterpart already at 3 h after injection. Importantly, 57Co-DOTA-ZEGFR:2377 demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for 68Ga-DOTA-ZEGFR:2377. The results of this study suggest that the positron-emitting cobalt isotope 55Co would be an optimal label for DOTA-ZEGFR:2377 and further development should concentrate on this radionuclide as a label.

PubMed Disclaimer

Conflict of interest statement

V.T., J.L., A.O., and S.S. are the members of the scientific advisory board of Affibody A.B. S.S. is a minority share owner of Affibody A.B. V.T., A.O. own stock in Affibody A.B. Affibody A.B. holds intellectual property rights and trademarks for Affibody molecules. J.G., K.G.A., J.H.D., B.B.O., H.T., J.B. and B.M. declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Inhibition of 111In-DOTA- ZEGFR:2377 binding to A431 cells with natGa-, natCo- or natIn- ZEGFR:2377. Data presented as mean ± SD of 3 culture dishes.
Figure 2
Figure 2
Cell-associated radioactivity as a function of time during continuous incubation of EGFR-expressing A431 cells with the 57Co-DOTA-ZEGFR:2377 (a) and 68Ga- DOTA-ZEGFR:2377 (b). Data are presented as mean from 3 dishes ± SD, and normalized to the maximum uptake. Due to small variability some error bars are hidden behind the symbols.
Figure 3
Figure 3
Specificity of 57Co-DOTA-ZEGFR:2377 (a) and 68Ga-DOTA-ZEGFR:2377 (b) uptake in tumours at 3 h after injection. An injected protein dose was adjusted to 40 µg for all animals. For pre-blocking, a group of animals bearing EGFR-positive A431 xenografts was pre-injected with 400 µg non-labelled ZEGFR:2377 40 min before injection of the radiolabelled conjugate. A group with SKOV-3 xenografts was used as a negative control. Data are presented as average %ID/g ± SD (n = 4).
Figure 4
Figure 4
Imaging of mice bearing A431 xenografts. PET/CT using 68Ga-DOTA-ZEGFR:2377 at 3 h after injection (a) and SPECT/CT using 57Co-DOTA-ZEGFR:2377 at 3 h (b) and 24 h (c) after injection. The images show three-dimensional volume rendering of PET or SPECT data overlaid CT data. The images were rotated to provide view of liver. The relative colour scales were normalized to the highest activity and then adjusted to provide first red pixel in tumours (8, 13 and 17% of the full scale, for Fig. 4a,b and c, respectively). Arrows point at tumours (Tu), kidneys (Ki) and livers (Li).
See this image and copyright information in PMC

References

    1. Avraham R, Yarden Y. Feedback regulation of EGFR signalling: decision making by early and delayed loops. Nat. Rev. Mol. Cell Biol. 2011;12:104–117. doi: 10.1038/nrm3048. - DOI - PubMed
    1. Carlsson, J. EGFR-Family Expression and Implications for Targeted Radionuclide Therapy in Targeted Radionuclide Tumor Therapy-Biological Aspects (ed. Stigbrand, T. et al.) 25–58 (Springer, 2008).
    1. Cappuzzo F, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J. Natl. Cancer Inst. 2005;97:643–655. doi: 10.1093/jnci/dji112. - DOI - PubMed
    1. Hirsch FR, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J. Clin. Oncol. 2006;24:5034–5042. doi: 10.1200/JCO.2006.06.3958. - DOI - PubMed
    1. Pirker R, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet. Oncol. 2012;13:33–42. doi: 10.1016/S1470-2045(11)70318-7. - DOI - PubMed

Publication types

Substances