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

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

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Abstrakt

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 (111)In-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 (57)Co (T1/2 = 271.8 d), (55)Co (T1/2 = 17.5 h), and, for comparison, with the positron-emitting radionuclide (68)Ga (T1/2 = 67.6 min) with preserved specificity of binding to EGFR-expressing A431 cells. The long-lived cobalt radioisotope (57)Co was used in animal studies. Both (57)Co-DOTA-ZEGFR:2377 and (68)Ga-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, (57)Co-DOTA-ZEGFR:2377 demonstrated a tumour-to-liver ratio of 3, which is 7-fold higher than the tumour-to-liver ratio for (68)Ga-DOTA-ZEGFR:2377. The results of this study suggest that the positron-emitting cobalt isotope (55)Co would be an optimal label for DOTA-ZEGFR:2377 and further development should concentrate on this radionuclide as a label.

OriginalsprogEngelsk
Artikelnummer5961
TidsskriftScientific Reports
Vol/bind7
Antal sider10
ISSN2045-2322
DOI
StatusUdgivet - 1. dec. 2017

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