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Laser scanning cytometry as a tool for biomarker validation

: Mittag, A.; Füldner, C.; Lehmann, J.; Tarnok, A.


Mahadevan-Jansen, A. ; Society of Photo-Optical Instrumentation Engineers -SPIE-, Bellingham/Wash.:
Advanced biomedical and clinical diagnostic systems XI : 3 - 5 February 2013, San Francisco, California, United States
Bellingham, WA: SPIE, 2013 (Proceedings of SPIE 8572)
ISBN: 978-0-8194-9341-5
Paper 85720O
Conference "Advanced Biomedical and Clinical Diagnostic Systems" <11, 2013, San Francisco/Calif.>
Conference Paper
Fraunhofer IZI ()

Biomarkers are essential for diagnosis, prognosis, and therapy. As diverse is the range of diseases the broad is the range of biomarkers and the material used for analysis. Whereas body fluids can be relatively easily obtained and analyzed, the investigation of tissue is in most cases more complicated. The same applies for the screening and the evaluation of new biomarkers and the estimation of the binding of biomarkers found in animal models which need to be transferred into applications in humans. The latter in particular is difficult if it recognizes proteins or cells in tissue. A better way to find suitable cellular biomarkers for immunoscintigraphy or PET analyses may be therefore the in situ analysis of the cells in the respective tissue. In this study we present a method for biomarker validation using Laser Scanning Cytometry which allows the emulation of future in vivo analysis. The biomarker validation is exemplarily shown for rheumatoid arthritis (RA) on synov ial membrane. Cryosections were scanned and analyzed by phantom contouring. Adequate statistical methods allowed the identification of suitable markers and combinations. The fluorescence analysis of the phantoms allowed the discrimination between synovial membrane of RA patients and non-RA control sections by using median fluorescence intensity and the "affected area". As intensity and area are relevant parameters of in vivo imaging (e.g. PET scan) too, the presented method allows emulation of a probable outcome of in vivo imaging, i.e. the binding of the target protein and hence, the validation of the potential of the respective biomarker.