Fluorine-18 labeling of ML04 – presently the most promising irreversible inhibitor candidate for visualization of EGFR in cancer

Abstract

Overexpression of the EGFR has been linked to cell malignancy, metastasis and poor prognosis thus making it a target for several FDA approved drugs such as Gefitinib and Erlotinib. Unfortunately, these drugs have yielded suboptimal clinical results. In order to evaluate and monitor EGFR-targeted treatment response at the molecular level, several PET biomarkers have been developed. One of the lead irreversible inhibitors (1) has been labeled with carbon-11, however the short half-life of this radioisotope limited the time window for in vivo studies. Compound 1 was successfully labeled with fluorine-18 via a multi-step radiosynthesis with 14% decay-corrected overall radiochemical yield, 98% radiochemical purity, specific activity of 1800 Ci/mmol (n=10) at end of bombardment, and a total radiosynthesis time of 4 h including purification and formulation. [18F]-1 will allow for prolonged in vivo studies including Micro-PET analysis of EGFR tumor-bearing animal models. Copyright © 2006 John Wiley & Sons, Ltd.