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Imaging Mass Spectrometry (IMS) using matrix-assisted laser desorption ionization (MALDI) is being investigated using a linear ion trap with the overall goal of analyzing the distribution of various targeted therapies within patients’ tumors. The drug chosen for evaluation here is erlotinib (Tarceva) which targets the epidermal growth factor receptor (EGFR), a type I receptor tyrosine kinase (TK) involved in cellular differentiation and proliferation, by binding to the ATP pocket and inhibiting the autophosphorylation of the receptor. Tarceva has demonstrated clinical activity in non-small cell lung cancer, head and neck cancer, and ovarian cancer in Phase II studies. The sensitivity and MSn capabilities of the Finnigan LTQ are exploited for the unambiguous determination of the distribution of this drug within human pancreatic tumors. Custom software was used to acquire data while rastering the tissue and data visualization software used to display the 2- and 3-dimensional images.
SCID mice bearing patients’ pancreas tumors grown as xenografts were dosed once with 2.5 mg Tarceva in 6% Captisol, or Captisol alone, delivered by oral gavage. Sixteen hours following the administration of treatment or the vehicle, the pancreas tumors were resected, snap frozen immediately, and then 10-μ-thick tissue sections were prepared with a cryotome and placed on various MALDI surfaces. Nebulized matrix was applied with a commercial airbrush. Peaks corresponding to the m/z of both Tarceva and its O-demethylated metabolite, OSI-420, were found distributed in Tarceva-treated tumor, but not in the control sample. Results from single reaction monitoring (SRM) experiments on the drug precursor at m/z 394 and the metabolite at m/z 380 were mapped to visualize the drug distribution within the tissue. The results confirm that the Finnigan LTQ with vMALDI source mass spectrometer can be used to localize Tarceva and its metabolite in a xeno-graft tumor model.