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

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 Tc-99m-7C12 and tumor burden and evaluated the possibility of using this probe to monitor tumor response to erlotinib. The specificity and affinity of Tc-99m-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 Tc-99m-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. Tc-99m-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 Tc-99m-7C12 showed good correlation with tumor burden. Erlotinib treatment resulted in a progressive reduction of tumor burden and tumor uptake of Tc-99m-7C12. Tc-99m-7C12 binds to EGFR with high affinity and specificity. Tumor uptake is correlated with tumor burden. Quantification of Tc-99m-7C12 uptake is promising for monitoring therapy response of EGFR-expressing tumors.