EGFR and its mutated variant EGFRvIII are over-expressed in 50% of glioblastoma multiforme: engineered versions of anti-EGFR and anti-EGFRvIII Nbs, modified to increase their valency and circulation half-life, have been successfully applied for the in vivo optical imaging of brain tumor in an orthotopic mouse model [145]. Here, EGFR is linked to brain neoplasm.