diffuse-optical-spectroscopy-for-quantitative-assessment-acute

Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and ...

Toronto Metropolitan University (Formerly Ryerson Univ.)

Ryerson University

Monitoring the onset of erythema following external beam radiation therapy has the potential to offer a means of managing skin toxicities via biological targeted agents - prior to full progression. However, current skin toxicity scoring systems are subjective and provide at best a qualitative evaluation. Here, we investigate the potential of diffuse optical spectroscopy (DOS) to provide quantitative metrics for scoring skin toxicity. A DOS fiberoptic reflectance probe was used to collect white light spectra at two probing depths using two short fixed source-collector pairs with optical probing depths sensitive to the skin surface. The acquired spectra were fit to a diffusion theory model of light transport in tissue to extract optical biomarkers (hemoglobin concentration, oxygen saturation, scattering power and slope) from superficial skin layers of nude mice, which were subjected to erythema inducing doses of ionizing radiation. A statistically significant increase in oxygenated hemoglobin (p < 0.0016) was found in the skin post-irradiation - confirming previous reports. More interesting, we observed for the first time that the spectral scattering parameters, A (p = 0.026) and k (p = 0.011), were an indicator of erythema at day 6 and could potentially serve as an early detection optical biomarker of skin toxicity. Our data suggests that reflectance DOS may be employed to provide quantitative assessment of skin toxicities following curative doses of external beam radiation.

Quantitative monitoring of radiation induced skin toxicities in nude mice using optical biomarkers measured from diffuse optical reflectance spectroscopy.

Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients' quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model.

Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model.

The highly tunable physical and optical properties and the ability to bind an ever expanding library of ligands have catapulted nanoparticles into nearly every discipline of scientific research. As nanoparticles inch closer to being fully deployed at the clinical level, some of the recent advances in the applications of nanoparticles in medicine are reviewed. From imaging and diagnostics to therapy and treatment, a variety of nanoparticles are presented along with their physical and optical properties to be used in a diverse array of medical applications. While other reviews are tailored to specific applications or to single nanoparticle types, this review aims to offer a more widespread view on visualization, diagnosis and treatment of disease with various types of nanoparticles.

Applications of nanoparticles in nanomedicine.

Gold nanoparticles (GNPs) are emerging as promising novel agents for cancer therapy. However, the oxygen concentration in human tumors is highly heterogeneous, and there are many regions with very low levels of oxygen (hypoxia). A majority of solid tumors contain regions with oxygen pressure values of less than 0.7% in the gas phase. The purpose of this study was to investigate NP stability, toxicity, and cellular uptake under hypoxic conditions. GNPs 50 nm in diameter were used, and the experiment was performed under 0.2% (hypoxic) and 21% (normoxic) oxygen levels using MCF-7 and HeLa cells. Hypoxic cells with prolonged exposure (eighteen hours) to hypoxia had a higher NP uptake at both 6- and 24-hour NP incubation time points. No significant toxicity was introduced by NPs under hypoxic and normoxic conditions. These findings will play a vital role in the optimization of GNP-based therapeutics in cancer treatment.

Article	Year
Quantitative monitoring of radiation induced skin toxicities in nude mice using optical biomarkers measured from diffuse optical reflectance spectroscopy. Biomedical optics express\| PubMed ID: 24876997	2014
Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model. BMC cancer\| PubMed ID: 25159192	2014
Applications of nanoparticles in nanomedicine. Journal of biomedical nanotechnology\| PubMed ID: 25992462	2014
Uptake of Gold Nanoparticles in Breathless (Hypoxic) Cancer Cells. Journal of biomedical nanotechnology\| PubMed ID: 26307839	2015

Darren Yohan

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