AVS 55th International Symposium & Exhibition
    Biological, Organic, and Soft Materials Focus Topic Wednesday Sessions
       Session BO+AS+BI-WeA

Paper BO+AS+BI-WeA11
Spatial Distribution Analysis of a Selenium Based Anti-Cancer Drug in Tumor Tissue Samples by ToF-SIMS

Wednesday, October 22, 2008, 5:00 pm, Room 201

Session: Advances in Surface Analytical Methods for Organic and Biological Interfaces
Presenter: S.A. Burns, University at Buffalo
Authors: S.A. Burns, University at Buffalo
M. Khin, Roswell Park Cancer Institute
L. Kazim, Roswell Park Cancer Institute
Y. Rustum, Roswell Park Cancer Institute
S. Cao, Roswell Park Cancer Institute
F. Durrani, Roswell Park Cancer Institute
J.A. Gardella, University at Buffalo
Correspondent: Click to Email

Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) has recently found new applications in the field of tissue analysis due to the advancement of cluster ion sources.1 Bi cluster primary ion sources have been shown to produce chemical images with high spatial resolution, to ca. 100nm. The use of C60 cluster ion sources for depth profile analysis distributes the ion impact force allowing for a more specialized analysis of organic samples.2 ToF-SIMS is an extremely useful application to detect low molecular weight drugs within a polymeric membrane. This study utilized this application to spatially image drug distribution of an anticancer agent in a two types of tissue samples. Nude mice implanted with human head and neck tumors were treated with methylselenocystein (MSC), a known anticarcinogen.3 MALDI imaging has been used to determine the distribution of another anti-cancer drug, CPT-11 when MSC has also been introduced.4 The distribution of CPT-11 was found to be more even throughout the tumor in the presence of MSC. This indicates that the MSC causes an increase the vasculature of a tumor thereby allowing other anti-cancer drugs to distribute evenly. MALDI imaging was able to show drug distribution but could not associate the fragment peak of the MSC with the vasculature of the cells due to restrictions in image resolution (100μm). ToF-SIMS imaging has been shown to reach resolutions of 100nm allowing for this type of analysis to be performed. MSC treated tumor and liver samples were analyzed using imaging and depth profiling to determine the distribution of drug with respect to the vasculature of the tissue. The first step of this study was to determine characteristic peaks from the MSC that could be identified in the tissue samples. Analysis of the livers and tumors of the mice that had been treated with MSC had fragment peaks with isotopic distributions indicating selenium containing organic compounds not found in the control samples. These fragment peaks were used as the drug peaks whose distribution in the tissue samples were compared to fragment peaks which could be attributed directly to cell vascular structure.

1Brunelle,A,et al. Journal of Mass Spectrometry 2005,40,985-999
2Fletcher,JS,et al. Analytical Chemistry 2006,78,1827-31
3Azrak,RG,et al. Biochemical Pharmacology 2007,73,1280-1287
4Prieto Conaway,MC,et al. Thermo Scientific 2008,Application Note.