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


METHODS
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.


CONCLUSIONS
(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.
Gainkam
Lea Olive Tchouate
LO
ICMI, In vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel (VUB), Brussels, Belgium. ltchouat@vub.ac.be
Keyaerts
Marleen
M
Caveliers
Vicky
V
Devoogdt
Nick
N
Vanhove
Christian
C
Van Grunsven
Leo
L
Muyldermans
Serge
S
Lahoutte
Tony
T
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures; D009369:Neoplasms / Q000628:therapy*; D014057:Tomography, X-Ray Computed
D066246:ErbB Receptors