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Correlation Between Epidermal Growth Factor Receptor-Specific Nanobody Uptake and Tumor Burden: A Tool for Noninvasive Monitoring of Tumor Response to Therapy

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Abstract

Purpose

Nanobodies represent an interesting class of probes for the generic development of molecular imaging agents. We studied the relationship between tumor uptake of the epidermal growth factor receptor (EGFR)-specific nanobody 99mTc-7C12 and tumor burden and evaluated the possibility of using this probe to monitor tumor response to erlotinib.

Procedures

The specificity and affinity of 99mTc-7C12 was determined on A431 cells. Cells expressing firefly luciferase were used to evaluate tumor burden using bioluminescence imaging. We evaluated the effect of erlotinib on tumor burden and 99mTc-7C12 uptake in vitro as well as in vivo. In vivo bioluminescence imaging was performed followed by pinhole single-photon emission computed tomography/micro-computed tomography.

Results

99mTc-7C12 binds specifically to the receptor with high affinity (3.67 ± 0.59 nM). Erlotinib reduced tumor uptake and cell viability in a concentration-dependent manner. Tumor uptake of 99mTc-7C12 showed good correlation with tumor burden. Erlotinib treatment resulted in a progressive reduction of tumor burden and tumor uptake of 99mTc-7C12.

Conclusion

99mTc-7C12 binds to EGFR with high affinity and specificity. Tumor uptake is correlated with tumor burden. Quantification of 99mTc-7C12 uptake is promising for monitoring therapy response of EGFR-expressing tumors.

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Acknowledgments

The research at ICMI is funded by the Interuniversity Attraction Poles Programme—Belgian State—Belgian Science Policy. Lea Olive Tchouate Gainkam is a Ph.D. fellow of the Horizontal Research Axis (HOA) grant of the Vrije Universiteit Brussel. Tony Lahoutte is a Senior Clinical Investigator of the Research Foundation—Flanders (FWO). Marleen Keyaerts is a Ph.D. fellow of the Research Foundation—Flanders (FWO). The authors acknowledge Ms. Cindy Peleman for her technical assistance with the small animal pinhole SPECT/micro-CT imaging. The authors are grateful to Lieven Huang for producing the nanobody.

Conflict of Interest Disclosure

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. ICMI, In vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium

    Lea Olive Tchouate Gainkam, Marleen Keyaerts, Vicky Caveliers, Nick Devoogdt, Christian Vanhove & Tony Lahoutte

  2. Department of Nuclear Medicine, UZ Brussel, Brussels, Belgium

    Marleen Keyaerts, Vicky Caveliers, Christian Vanhove & Tony Lahoutte

  3. Department of Cell Biology, Vrije Universiteit Brussel, Brussels, Belgium

    Leo Van Grunsven

  4. Department of Molecular and Cellular Interactions, Flanders Institute for Biotechnology (VIB), Ghent, Belgium

    Serge Muyldermans

  5. Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium

    Serge Muyldermans

Authors
  1. Lea Olive Tchouate Gainkam
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  2. Marleen Keyaerts
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Corresponding author

Correspondence to Lea Olive Tchouate Gainkam.

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Manuscript Category and Significance:

Original article that investigates the relationship between tumor burden and uptake of radiolabeled 7C12 nanobody in response to an EGFR tyrosine kinase inhibitor. The preclinical data presented here strongly suggest that it will be feasible to monitor tumor response to therapy in clinical trial using this molecular imaging probe.

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Tchouate Gainkam, L.O., Keyaerts, M., Caveliers, V. et al. Correlation Between Epidermal Growth Factor Receptor-Specific Nanobody Uptake and Tumor Burden: A Tool for Noninvasive Monitoring of Tumor Response to Therapy. Mol Imaging Biol 13, 940–948 (2011). https://doi.org/10.1007/s11307-010-0428-4

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  • DOI: https://doi.org/10.1007/s11307-010-0428-4

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