Localization,mechanism and reduction of renal retention of technetium‐99m labeled epidermal growth factor receptor‐specific nanobody in mice |
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| Authors: | Lea Olive Tchouate Gainkam Vicky Caveliers Nick Devoogdt Christian Vanhove Catarina Xavier Otto Boerman Serge Muyldermans Axel Bossuyt Tony Lahoutte |
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| Institution: | 1. ICMI, In vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel, Brussels, Belgium;2. Nuclear Medicine Department, UZ Brussel, Brussels, Belgium;3. Department of Nuclear Medicine, Radboud University Hospital, Nijmegen, The Netherlands;4. Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium |
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| Abstract: | Background 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. Methods 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. Results 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. Conclusion 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. |
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| Keywords: | nanobody lysine gelofusine kidneys megalin |
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