Abstract 203: Visualization of drug delivery by using high resolution microscopic mass spectrometry

Abstract

Abstract Pharmacokinetic (PK) and pharmacodynamic (PD) studies are important to evaluate the efficacy and toxicity of the drugs. In these analyses, tissue homogenates are generally used for the quantification by high-performance liquid chromatography (HPLC) or liquid chromatography mass spectrometry (LC-MS). However, they lack the information regarding the drug distribution in a specific anatomical area. The information of the drug distribution allows us to optimize the drug design enabling more efficient targeted delivery. We studied the tissue distribution of paclitaxel (PTX) and its micellar formulation (NK105) using a microscopic mass spectroscopy (MMS). A MMS in which a microscope is coupled with an atmospheric pressure matrix-assisted laser desorption/ionization (MALDI) and quadruple ion trap time-of-flight (TOF) analyser was used. The matrix-coated drug sample is ionised and then separated on the basis of its mass-to-charge ratio (m/z). Images were acquired from imaging mass spectrometry (IMS) or tandem mass spectrometry (MS/MS) data. (1) We established the drug imaging system with enhanced resolution and sensitivity. In the analysis, MS and MS/MS were used for quantification and validation, respectively. (2) NK105 showed much stronger antitumor effects on a human pancreatic cancer BxPC3 xenograft than PTX. In the drug imaging, we demonstrated that NK105 delivered more PTX to the whole tumor tissue (including the center lesion). In the mouse model, PTX caused the peripheral neurotoxicity but NK105 did not. Multiple high drug-signal areas surrounding and inside the caudal nerve were observed in the case of PTX, whereas the signals after NK105 injection were significantly low. We succeeded in visualising the EPR (Enhanced Permeability and Retention) effect using MMS. The data obtained by the drug imaging may be useful for facilitating DDS-drug design. The significance of microscopic mass spectrometry with high resolution in the visualisation of drug distribution. Sci Rep. 3:3050. 2013. Citation Format: Masahiro Yasunaga, Masaru Furuta, Koretsugu Ogata, Yoshikatsu Koga, Yasuhiro Matsumura. Visualization of drug delivery by using high resolution microscopic mass spectrometry. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 203. doi:10.1158/1538-7445.AM2015-203