Correlation between epidermal growth factor receptor-specific nanobody uptake and tumor burden: a tool for noninvasive monitoring of tumor response to therapy.

TitleCorrelation between epidermal growth factor receptor-specific nanobody uptake and tumor burden: a tool for noninvasive monitoring of tumor response to therapy.
Publication TypeJournal Article
Year of Publication2011
AuthorsGainkam, L. Olive Tcho, M. Keyaerts, V. Caveliers, N. Devoogdt, C. Vanhove, L. Van Grunsven, S. Muyldermans, and T. Lahoutte
JournalMol Imaging Biol
Volume13
Issue5
Pagination940-8
Date Published2011 Oct
ISSN1860-2002
KeywordsAnimals, Blotting, Western, Cell Line, Tumor, Humans, Male, Mice, Mice, Nude, Nanostructures, Neoplasms, Receptor, Epidermal Growth Factor, Tomography, X-Ray Computed
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 (99m)Tc-7C12 and tumor burden and evaluated the possibility of using this probe to monitor tumor response to erlotinib.PROCEDURES: The specificity and affinity of (99m)Tc-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 (99m)Tc-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: (99m)Tc-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 (99m)Tc-7C12 showed good correlation with tumor burden. Erlotinib treatment resulted in a progressive reduction of tumor burden and tumor uptake of (99m)Tc-7C12.CONCLUSION: (99m)Tc-7C12 binds to EGFR with high affinity and specificity. Tumor uptake is correlated with tumor burden. Quantification of (99m)Tc-7C12 uptake is promising for monitoring therapy response of EGFR-expressing tumors.

DOI10.1007/s11307-010-0428-4
Alternate JournalMol Imaging Biol
PubMed ID20865332