title: Correlation between epidermal growth factor receptor-specific nanobody uptake and tumor burden: a tool for noninvasive monitoring of tumor response to therapy.
abstract: 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.
authors.affiliation: ICMI, In vivo Cellular and Molecular Imaging Laboratory, Vrije Universiteit Brussel (VUB), Brussels, Belgium. ltchouat@vub.ac.be
authors.forename: Lea Olive Tchouate
authors.initials: LO
authors.lastname: Gainkam
authors.forename: Marleen
authors.initials: M
authors.lastname: Keyaerts
authors.forename: Vicky
authors.initials: V
authors.lastname: Caveliers
authors.forename: Nick
authors.initials: N
authors.lastname: Devoogdt
authors.forename: Christian
authors.initials: C
authors.lastname: Vanhove
authors.forename: Leo
authors.initials: L
authors.lastname: Van Grunsven
authors.forename: Serge
authors.initials: S
authors.lastname: Muyldermans
authors.forename: Tony
authors.initials: T
authors.lastname: Lahoutte
mesh_terms: 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
chemical_list: D066246:ErbB Receptors