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Overexpression of the epidermal growth factor receptor (EGFR) occurs with high incidence in various carcinomas. The oncogenic expression of the receptor has been exploited for immunoglobulin-based diagnositcs and therapeutics. We describe the use of a llama single-domain antibody fragment, termed Nanobody, for the in vivo radioimmunodetection of EGFR overexpressing tumors using single photon emission computed tomography (SPECT) in mice.
Fluorescence-activated cell sorting (FAC) analysis was performed to evaluate the specificity and selectivity of 8B6 Nanobody to bind EGFR on EGFR overexpressing cells. The nanobody was then labeled with 99mTc via its C-terminal histidine tail. Uptake in normal organs and tissues was assessed by ex vivo analysis. In vivo tumor targeting of 99mTc-8B6 Nanobody was evaluated via pinhole SPECT in mice bearing xenografts of tumor cells with either high (A431) or moderate (DU 145) overexpression of EGFR.
FACS analysis indicated that the 8B6 Nanobody only recognizes cells overexpressing EGFR. In vivo blood clearance of 99mTc-8B6 Nanobody is relatively fast (half-life, 1.5h) and mainly via the kidneys. At 3h postinjection, total kidney accumulation is high(46.6+0.9%IA) compared to total liver uptake (18.9+0.6IA). Pinhole SPECT imaging of mice bearing A431 xenografts showed higher average tumor uptake (5.2+0.5%IA/cm3) of 99mTc-8B6 Nanobody compared to DU145 xenografts (1.8+0.3%IA/cm3, pConclusion :
The EGFR-binding Nanobody investigated in this study shows high specificity and selectivity towards EGFR overexpressing cells. Pinhole SPECT analysis with 99mTc-8B6 Nanobody enabled in vivo discrimination between tumors with high and moderate EGFR overexpression. The favorable biodistribution further corroborates the suitability of Nanobodies for in vivo tumor imaging.
|Number of pages||9|
|Journal||Molecular Imaging and Biology|
|Publication status||Published - 1 May 2008|
- tumor targeting
- molecular imaging
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- 4 Finished
DWTC238: NIMI Non-invasive quantitative molecular imaging with applications for studying cellular process
Bossuyt, A., Mortelmans, L., Philips, W., Van Der Linden, A. & Gallez, B.
1/01/07 → 31/03/12