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A first synthesis of [18F]Lapatinib: a potential tracer for positron emission tomographic imaging of ErbB1/ErbB2 tyrosine kinase activity

Wednesday, October 26, 2011 — Poster Session III

10:00 a.m. – Noon

Natcher Conference Center




  • F Basuli
  • H Wu
  • C Li
  • Z Shi
  • A Sulima
  • GL Griffiths


Lapatinib ditosylate (Tykerb®) is a dual ErbB1/ErbB2 tyrosine kinase inhibitor from GlaxoSmithKline approved for treatment of advanced metastatic breast cancer. Lapatinib contains a fluorine atom in a meta- position on one benzyl ring, and ideally, if an 18F atom could be exchanged here it would result in a chemically identical radiofluorinated analog of the approved drug. We based our approach to [18F]Lapatinib on ether bond formation between meta-[18F]fluorobenzylbromide and a Boc-protected Lapatinib fragment, tert-butyl (5-(4-(3-chloro-4-hydroxyphenylamino)quinazolin-6-yl)furan-2-yl)methyl(2-(methylsulfonyl)ethyl)carbamate, containing a phenolic group, followed by deprotection of the N-Boc secondary amino protecting group with TFA. The N-Boc-protected Lapatinib precursor was synthesized following a literature method with modifications. Fluorine-18 labeled meta-fluorobenzylbromide was prepared according to the literature method published by our group. Treatment of a DMF solution of meta-[18F]fluorobenzylbromide with Boc-protected Lapatinib precursor fragment in the presence of K2CO3 at 110 oC for 10 minutes in a microwave followed by Boc deprotection with TFA afforded [18F]Lapatinib (65%, uncorrected, isolated). The overall radiochemical yield of the reaction starting from the radiofluorination of the iodonium salt was 5-10% (uncorrected) in a 130 minute synthesis time. Full details of the synthetic and analytical procedures along with further background and implications to the work will be presented.

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