Localization, mechanism and reduction of renal retention of technetium-99m labeled epidermal growth factor receptor-specific nanobody in mice
Article first published online: 8 OCT 2010
Copyright © 2010 John Wiley & Sons, Ltd.
Contrast Media & Molecular Imaging
Volume 6, Issue 2, pages 85–92, March/April 2011
How to Cite
Tchouate Gainkam, L. O., Caveliers, V., Devoogdt, N., Vanhove, C., Xavier, C., Boerman, O., Muyldermans, S., Bossuyt, A. and Lahoutte, T. (2011), Localization, mechanism and reduction of renal retention of technetium-99m labeled epidermal growth factor receptor-specific nanobody in mice. Contrast Media Mol Imaging, 6: 85–92. doi: 10.1002/cmmi.408
- Issue published online: 13 APR 2011
- Article first published online: 8 OCT 2010
- Manuscript Accepted: 17 JUN 2010
- Manuscript Revised: 5 JUN 2010
- Manuscript Received: 4 FEB 2010
- Interuniversity Attraction Poles Programme, Belgian State, Belgian Science Policy
- Horizontal Research Axis (HOA) grant of the Vrije Universiteit Brussel
Nanobodies are single-domain antigen binding fragments derived from functional heavy-chain antibodies elicited in Camelidae. They are powerful probes for radioimmunoimaging, but their renal uptake is relatively high. In this study we have evaluated the role of megalin on the renal uptake of anti-EGFR 99mTc-7C12 nanobody and the potency of gelofusine and/or lysine to reduce renal uptake of 99mTc-7C12.
First we compared the renal uptake of 99mTc-7C12 in megalin-deficient and megalin-wild-type mice using pinhole SPECT/microCT and ex vivo analysis. The effect of gelofusine and lysine administration on renal accumulation of 99mTc-7C12 was analyzed in CD-1 mice divided into lysine preload at 30 min before tracer injection (LysPreload), LysPreload + gelofusine coadministration (LysPreload + GeloCoad), lysine coadministration (LysCoad), gelofusine coadministration (GeloCoad) and LysCoad + GeloCoad. The combined effect of gelofusine and lysine on tumor uptake was tested in mice xenografts.
Renal uptake of 99mTc-7C12 was 44.22 ± 3.46% lower in megalin-deficient compared with megalin-wild-type mice. In CD-1 mice, lysine preload had no effect on the renal retention whereas coinjection of lysine or gelofusine with the tracer resulted in 25.12 ± 2.99 and 36.22 ± 3.07% reduction, respectively. The combined effect of gelofusine and lysine was the most effective, namely a reduction of renal retention of 45.24 ± 2.09%. Gelofusine and lysine coadministration improved tumor uptake.
Megalin contributes to the renal accumulation of 99mTc-7C12. Gelofusine and lysine coinjection with the tracer reduces the renal uptake while tumor uptake is improved. Although this methodology allows for optimization of imaging protocol using nanobodies, further improvements are needed before using these molecules for radionuclide therapy. Copyright © 2010 John Wiley & Sons, Ltd.