Synthesis of [¹¹C]gefitinib for imaging epidermal growth factor receptor tyrosine kinase with positron emission tomography

We have synthesized N-(3-chloro-4-fluorophenyl)-7-[¹¹C]methoxy- 6-[3-(morpholin-4-yl)propoxy]quinazolin-4-amine, [¹¹C]gefitinib ([¹¹C]Iressa), a high affinity (IC₅₀ = 2 nM) inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK), in solution and in a semi-automated stainless loop methylation system using [ ¹¹C]methyl triflate. The trapping efficiency for [ ¹¹C]methyl triflate in solution was higher than in the solvent film generated in the loop system, thus the overall radiochemical yield was considerably higher for the synthesis in solution. The average radiochemical yield for the solution chemistry was 15% with an average specific radioactivity of approximately 9000 mCi/μmole at EOS in one step from its corresponding desmethyl phenol precursor.