Evaluation of [ 18 F]gefitinib as a molecular imaging probe for the assessment of the epidermal growth factor receptor status in malignant tumors

摘要: Gefitinib, an inhibitor of the epidermal growth factor receptor–tyrosine kinase (EGFR-TK), has shown potent effects in a subset patients carrying specific EGFR-TK mutations advanced non-small-cell lung cancer. In this study, we asked whether PET with [18F]gefitinib may be used to study noninvasively pharmacokinetics gefitinib vivo and image EGFR status cancer cells. Synthesis been previously described. The biodistribution metabolic stability was assessed mice vervet monkeys for up 2 h post injection by both micropositron emission tomography (PET)/computed (CT) scans postmortem ex tissue harvesting. Uptake levels radiolabeled EGFR-expressing human cell lines various expression or mutation were evaluated vitro. MicroPET/CT two species demonstrated rapid predominantly hepatobiliary clearance vivo. However, uptake gefitinib, vitro, did not correlate functional status. This unexpected observation due high nonspecific, nonsaturable cellular gefitinib. drug analogue suggests that it assess imaging. is clinical relevance, as insufficient intratumoral concentrations are considered resistance therapy. highly nonspecific binding preclude use imaging probe noninvasive assessment receptor patients.