Laser postionization secondary neutral mass spectrometry in tissue: a powerful tool for elemental and molecular imaging in the development of targeted drugs

Abstract

The exact intracellular localization and distribution of molecules and elements becomes increasingly important for the development of targeted therapies and contrast agents. We show that laser postionization secondary neutral mass spectrometry (laser-SNMS) is well suited to localize particular elements and small molecules with subcellular spatial resolution applying the technique exemplary to Boron Neutron Capture Therapy (BNCT). We showed in a murine sarcoma that the drugs used for clinical BNCT, namely l-para-boronophenylalanine (700 mg/kg body weight i.p.) and sodium mercaptoundecahydro-closo-dodecaborate (200 mg/kg body weight i.p.), transport the therapeutic agent (10)B into the cytoplasm and into the nucleus itself, the most sensitive area of the cell. Sodium mercaptoundecahydro-closo-dodecaborate distributes (10)B homogeneously and l-para-boronophenylalanine heterogeneously. When combining laser-SNMS with prompt gamma-ray analysis as a screening technique, strategies for BNCT can be elaborated to develop new drugs or to improve the use of existing drugs on scientifically based evidence. The study shows the power of laser-SNMS in the early stages of drug development, also outside BNCT.