Imaging of atomic and molecular species in tissue with Laser-SNMS for pharmaceutical studies

The success of several anti-cancer therapies as well as other therapeutic and diagnostic strategies relies on the ability to selectively deliver compounds to target cells while sparing normal tissue. For many applications, however, current analytical methods lack the sensitivity and selectivity necessary to determine the distribution of pharmaceutical ultra-trace compounds within tissues with sub-cellular resolution. Laser secondary neutral mass spectrometry (Laser-SNMS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) are capable of detecting atoms and molecules with high sensitivity and a spatial resolution of up to 100 nm. The use of such methods requires special preparation techniques which preserve the morphological and chemical integrity of the living cell. Laser-SNMS was used to verify the effectiveness of the delivery process for various pharmaceutical compounds in animal studies. After injection of the pharmaceuticals, different types of mouse tissue such as brain, kidney and tumors were extracted, then prepared on a special specimen carrier and subsequently plunged with high velocity into LN₂-cooled propane for cryofixation. After trimming, the tissue block was freeze-dried. For postionization of sputtered neutrals, a laser beam with a wavelength of 193 nm was used. Ion-induced electron images showed that the structural and chemical integrity of the cells had been preserved. Cell-specific elemental and molecular signals could be used to identify individual cells and cell nuclei. The obtained data yield information about the distribution of the pharmaceutical products in different kinds of tissue.