Cancer Metastasis Rev DOI 10.1007/s10555-013-9489-6

Emerging technology: applications of Raman spectroscopy for prostate cancer Rachel E. Kast & Stephanie C. Tucker & Kevin Killian & Micaela Trexler & Kenneth V. Honn & Gregory W. Auner

# Springer Science+Business Media New York 2014

Abstract There is a need in prostate cancer diagnostics and research for a label-free imaging methodology that is nondestructive, rapid, objective, and uninfluenced by water. Raman spectroscopy provides a molecular signature, which can be scaled from micron-level regions of interest in cells to macroscopic areas of tissue. It can be used for applications ranging from in vivo or in vitro diagnostics to basic science laboratory testing. This work describes the fundamentals of Raman spectroscopy and complementary techniques including surface enhanced Raman scattering, resonance Raman spectroscopy, coherent anti-Stokes Raman spectroscopy, confocal Raman spectroscopy, stimulated Raman scattering, and spatially offset Raman spectroscopy. Clinical applications of Raman spectroscopy to prostate cancer will be discussed, including screening, biopsy, margin assessment, and monitoring of treatment efficacy. Laboratory applications including cell identification, culture monitoring, therapeutics development, and live imaging of cellular processes are discussed. Potential future avenues of research are described, with emphasis on multiplexing Raman spectroscopy with other modalities. R. E. Kast : K. Killian : M. Trexler : G. W. Auner (*) Smart Sensors and Integrated Microsystems Laboratories, Department of Electrical and Computer Engineering, Wayne State University, 5050 Anthony Wayne Drive, Room 3100, Detroit, MI 48202, USA e-mail: [email protected] S. C. Tucker : K. V. Honn Bioactive Lipids Research Program (BLRP), Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48202, USA S. C. Tucker : K. V. Honn : G. W. Auner Karmanos Cancer Institute, Detroit, MI, USA G. W. Auner Department of Surgery, Wayne State University School of Medicine, Detroit, MI 48202, USA

Keywords Raman spectroscopy . Prostate cancer . Diagnostics . Biomarkers . Therapeutics

1 Introduction The detection of prostate cancer has increased, and diseasespecific mortality rates have decreased since introduction of the prostate-specific antigen (PSA) blood test and subsequent greater use of early interventions [1, 2]. Common treatments include watchful waiting (expectant management or active surveillance), surgery to remove the prostate gland (radical prostatectomy), external beam radiation therapy, interstitial radiation therapy (brachytherapy), and androgen deprivation. Patient treatment decisions incorporate physician recommendations, estimated likelihood of cancer progression without early intervention, and treatment-related convenience, costs, and potential for eradication and adverse effects [3]. However, PSA blood tests vary in efficacy and reliability as a prostate cancer predictor and have many confounding problems that may cause false positive or false negative outcomes such as drug-induced PSA changes and elevated PSA due to nonmalignant conditions. Computed tomography scans provide poor tissue contrast and therefore lack the sensitivity and specificity required for diagnosis. Magnetic resonance imaging (MRI), while providing good contrast in soft tissue, is expensive as a general screening tool and has a high false positive rate. Other more exotic techniques such as PET scans are expensive and lack spatial resolution. Current ultrasound technology lacks spatial resolution and specificity. In fact, many of the standard diagnostic and treatment modalities in prostate cancer are out of date, inefficient, provide unreliable results, and/or do not differentiate the fundamental aspects of this disease. Therefore, new investigative tools are needed to aid in expanding the understanding of prostate cancer and to guide in the development of new diagnostic and treatment tools.

Cancer Metastasis Rev

The majority of fundamental investigative tools require cellular destruction or selective tagging, thereby negating nonintrusive in vivo or in vitro studies. Many methods use a unilateral approach, where a systemic understanding of the local and extended microenvironment is necessary. For example, mass spectroscopy can indirectly provide molecular composition. However, it is a complex and destructive technology where the cells are dissociated and the relative components are differentiated and interpreted by mass selection. Polymerase chain reaction (PCR) is another fundamental technique. Again, the cellular information is derived by the destruction of the cell and analysis of the genetic components, and it requires specific primers for the genetic sequence under investigation. Other techniques such as selective tagging of proteins via fluorescent markers can discern precise constituent makeup and location in vivo or through flow cytometry. However, this requires development of selective tags, and the binding of tags may interfere with the investigation of normal cellular processes. A technique that can provide molecular information on viable cells without tags would thus be valuable. Further, information on both inter- and intra-cellular processes and composition in live environments may provide a more systemic view of the cancer process. Nondestructive techniques such as infrared spectrometry provide information by inelastic scattering interactions with molecular dipoles. As such, it is very sensitive to water, which can overwhelm the spectral signals of other constituents in biological systems. Raman spectroscopy provides a molecular signature and can be scaled from micron measurements in single cells to macroscopic regions of tissue. It is ideal for biological studies because it is a nondestructive, rapid method of understanding molecular and chemical information often without need for tagging or other sample preparation, and it is not greatly influenced by the presence of water (Table 1). Its applications to prostate cancer are broad: from tissue diagnosis and margin assessment to therapeutic development and basic science research. This work describes the many ways Raman spectroscopy has already been applied to prostate cancer and the potential for new avenues of research.

2 Raman spectroscopy and complementary techniques 2.1 Raman spectroscopy The Raman effect was first predicted by A. Smekal in 1923 [4] and experimentally shown by C.V. Raman and K.S. Krishnan in 1928 [5, 6]. Raman spectroscopy is complementary to infrared (IR) spectroscopy. Raman spectroscopy is based on changes in the polarizability of vibrating molecules, whereas infrared spectroscopy is based on changes in the dipole moment. When light is incident on a sample, it is typically scattered back at the same wavelength and energy, an effect known as Rayleigh scattering [7]. However, approximately 1 in 107 photons create a change in polarizability in a molecule in the sample. This occurs when the incoming photon causes a momentary distortion of the electron distribution around a bond in a molecule, which is followed by reemission of the radiation (photon) as the bond returns to its normal state. This reemission causes (1) temporary polarization of the bond and (2) an induced dipole that disappears upon relaxation. Conversely, IR-active bonds undergo a change in the dipole moment. In a molecule with a center of symmetry, a change in dipole is accomplished by loss of the center of symmetry, while symmetry is preserved with a change in polarizability. Thus, in a centrosymmetric molecule, asymmetrical stretching and bending will be IR active and Raman inactive, while symmetrical stretching and bending will be Raman active and IR inactive. Hence, in a centrosymmetric molecule, IR and Raman spectroscopy are in general mutually exclusive, as summarized in Table 2. For molecules without a center of symmetry, each vibrational mode may be IR active, Raman active, both, or neither. However, symmetrical stretches and bends tend to be Raman active. The polarization change induced by molecular vibrational modes is a quantum mechanical phenomenon. The interaction can both subtract energy and add energy to the emitted photon as compared to the incoming excitation energy of the photon, resulting in a so called anti-Stokes or Stokes

Table 1 Comparison between Raman spectroscopy and other techniques

Spatial resolution Destructive Real time Dyes, tags, or other labels Extensive sample preparation Influenced by water Surface

Raman

FTIR

GC/MS

PCR

H&E/pathology

Emerging technology: applications of Raman spectroscopy for prostate cancer.

There is a need in prostate cancer diagnostics and research for a label-free imaging methodology that is nondestructive, rapid, objective, and uninflu...
966KB Sizes 2 Downloads 0 Views