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Showing content from https://pubmed.ncbi.nlm.nih.gov/35326686/ below:

Raman Spectroscopy in Prostate Cancer: Techniques, Applications and Advancements

Review

. 2022 Mar 17;14(6):1535. doi: 10.3390/cancers14061535. Raman Spectroscopy in Prostate Cancer: Techniques, Applications and Advancements

Affiliations

¹ Department of Urology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow G51 4TF, UK.
² School of Medicine, University of Glasgow, Glasgow G12 8QQ, UK.
³ Department for Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1RD, UK.
⁴ Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK.
⁵ CRUK Beatson Institute, Bearsden, Glasgow G61 1BD, UK.

PMID: 35326686
PMCID: PMC8946151
DOI: 10.3390/cancers14061535

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Review

Raman Spectroscopy in Prostate Cancer: Techniques, Applications and Advancements

Fortis Gaba et al. Cancers (Basel). 2022.

. 2022 Mar 17;14(6):1535. doi: 10.3390/cancers14061535. Affiliations

¹ Department of Urology, Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde, Glasgow G51 4TF, UK.
² School of Medicine, University of Glasgow, Glasgow G12 8QQ, UK.
³ Department for Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1RD, UK.
⁴ Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, UK.
⁵ CRUK Beatson Institute, Bearsden, Glasgow G61 1BD, UK.

PMID: 35326686
PMCID: PMC8946151
DOI: 10.3390/cancers14061535

Item in Clipboard

Abstract

Optical techniques are widely used tools in the visualisation of biological species within complex matrices, including biopsies, tissue resections and biofluids. Raman spectroscopy is an emerging analytical approach that probes the molecular signature of endogenous cellular biomolecules under biocompatible conditions with high spatial resolution. Applications of Raman spectroscopy in prostate cancer include biopsy analysis, assessment of surgical margins and monitoring of treatment efficacy. The advent of advanced Raman imaging techniques, such as stimulated Raman scattering, is creating opportunities for real-time in situ evaluation of prostate cancer. This review provides a focus on the recent preclinical and clinical achievements in implementing Raman-based techniques, highlighting remaining challenges for clinical applications. The research and clinical results achieved through in vivo and ex vivo Raman spectroscopy illustrate areas where these evolving technologies can be best translated into clinical practice.

Keywords: Raman spectroscopy; biomarker; diagnostics; prostate cancer; therapeutics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures
Figure 1

Applications of Raman spectroscopy in…

Figure 1

Applications of Raman spectroscopy in prostate cancer disease. ( A ) Energy level…

Figure 1

Applications of Raman spectroscopy in prostate cancer disease. (A) Energy level diagrams for light scattering. In Rayleigh scattering, photons are scattered with the same energy, and hence frequency, as the incident photons. Raman scattering results in an energy transfer from the incident photons to the chemical bond (Stokes Raman scattering) or from the vibrationally excited chemical bonds to the incident photons (anti-Stokes Raman scattering). Thus, Stokes Raman scattering results in photons with a lower energy than the incident photons, whilst anti-Stokes Raman scattering results in photons of a higher energy than the incident photons. (B) A schematic diagram of a Raman microscope. Raman microscopes consist of the following components: a laser source generating monochromatic light, a microscope setup with an objective lens to focus the laser beam and sample stage to enable mapping of the sample (the objective lens also collects the Raman scattered photons in backscattering configuration), a Rayleigh filter to remove the Rayleigh scattered light (the excitation wavelength), a pinhole for confocal sectioning of the target sample which removes out-of-focus light, a diffraction grating which separates the photons according to wavelength, and typically, a charge couple device (CCD) detector to capture the intensity of photons at each wavelength.

Figure 2

Raman spectroscopy of PC-3 cells.…

Figure 2

Raman spectroscopy of PC-3 cells. The Raman spectrum was acquired from a live…

Figure 2

Raman spectroscopy of PC-3 cells. The Raman spectrum was acquired from a live PC-3 cell using a 532 nm laser excitation source, which was focused onto the sample using a 60× objective lens (18 mW) for 10 s. Ratiometric Raman mapping of live PC-3 cells using the same acquisition settings except spectra were acquired for 0.5 s per pixel, with a 1 μm pixel size for imaging. The images present the lipid/protein ratios using the following Raman bands: 2851 cm⁻¹ (CH₂ symmetric stretch, lipids), 2880 cm⁻¹ (CH₂ asymmetric stretch, lipids and proteins) and 2930 cm⁻¹ (CH₃ symmetric stretch, proteins), based on formulae accompanying each panel. Nuclear regions are identified with a lower ratio than the surrounding cytoplasm, which is lipid-rich. Scale bars: 10 μm.

Figure 3

Biomolecular targeting using SERS detection.…

Figure 3

Biomolecular targeting using SERS detection. ( A ) Conceptual design of SERS nanoparticles…

Figure 3

Biomolecular targeting using SERS detection. (A) Conceptual design of SERS nanoparticles for biological analysis. Typically, a gold nanoparticle, in this case a nanostar, is coated in a Raman reporter molecule. The reporter usually has a large Raman cross-section and may have an absorption matched to the excitation wavelength for enhanced detection sensitivity via resonance coupling effects. The nanoparticle may be coated in a thin silica shell, which stabilises the gold core and also provides a matrix for the Raman reporter. Specific targeting is achieved through a targeting ligand, e.g., antibodies, DNA, micro-RNA, etc., which can be introduced through a linker group. (B) Detection of prostate-specific antigen (PSA) using a microfluidic device with a SERS limit-of-detection at 0.01 ng/mL. Adapted from [9] with permission from the American Chemical Society (copyright 2019). (C) Detection of prostate-specific membrane antigen (PSMA) using SERS nanostars functionalised with 4-aminothiophenol in five different LNCaP cancer cells, which express PSMA, whilst a specificity comparison with SERS spectra from individual LNCaP and PC3 cells (which do not express PSMA) is also provided. Adapted from [10] with permission from the American Chemical SocietySociety (copyright 2018).

Figure 4

( A ) Schematic diagram…

Figure 4

( A ) Schematic diagram detailing the excitation and collection configuration for conventional…

Figure 4

(A) Schematic diagram detailing the excitation and collection configuration for conventional (backscattered) Raman, where the laser excitation and Raman scattered photon collection are at the same point. In a conventional SORS experiment, the point of collection is offset from the excitation by a spatial offset (Δs). Adapted from [15] with permission from the Royal Society of Chemistry (copyright 2021). (B) Non-invasive in vivo imaging of integrin-targeting SERRS nanoparticles through the skull in GBM-bearing mice by means of conventional Raman (CR) and SORS. Representative CR and SORS spectra from a point of maximum intensity of the SERRS NPs are provided in (B). (C) 2D axial T2-weighted MRI scan confirming the presence of a left frontal tumour (outlined in red). SORS heatmap of the bone (greyscale) and SORS heatmap of the SERRS NPs (red hot) are overlaid and correlate with the tumour region highlighted in the MRI scan. Images reproduced from [17] with permission from Ivyspring International Publisher (copyright 2019).

Figure 5

SRS imaging of live PC-3…

Figure 5

SRS imaging of live PC-3 cells. Images were acquired at 2930 cm ^−1…

Figure 5

SRS imaging of live PC-3 cells. Images were acquired at 2930 cm⁻¹ (CH₃ symmetric stretch, proteins), 2880 cm⁻¹ (CH₂ asymmetric stretch, proteins and lipids) and 2851 cm⁻¹ (CH₂ symmetric stretch, lipids). A ratiometric image of the CH₂/CH₃ (2851 cm⁻¹/2930 cm⁻¹, intensity scale 0–0.8 a.u.) is provided which resolves the nucleus (<0.2) and lipid droplets (>0.7) within the cells. Scale bars: 10 μm. SRS imaging of a de-waxed tissue microarray (TMA) is also presented. SRS images were acquired at 2930 cm⁻¹ (CH₃), 2851 cm⁻¹ (CH₂) and 3010 cm⁻¹ (=CH). A wax-embedded TMA core imaged at 2851 cm⁻¹ (CH₂) shows signal intensity across the core arising from the wax.

Figure 6

( A ) Average Raman…

Figure 6

( A ) Average Raman spectra for benign ( n = 776) and…

Figure 6

(A) Average Raman spectra for benign (n = 776) and malignant (n = 149) tissues. Corresponding peaks are shown with black arrows. (B) Receiver operating characteristic (ROC) curve distinguishing benign from malignant tissue with an accuracy of 86%. SEN, sensitivity; SPE, specificity; AUC, area under the curve. Univariate analysis performed on Raman peaks are illustrated with p values: *** p < 0.001, ** p < 0.01. Images reproduced from [36] with permission from Wiley (copyright 2018).