In vivo detection of changes in cutaneous carotenoids after chemotherapy using shifted excitation resonance Raman difference and fluorescence spectroscopy

Abstract

Background Various cutaneous toxicities under chemotherapy indicate a local effect of chemotherapy by secretion after systemic application. Here, changes in the fluorescence and Raman spectral properties of the stratum corneum subsequent to intravenous chemotherapy were assessed. Methods Twenty healthy subjects and 20 cancer patients undergoing chemotherapy were included. Measurement time points in cancer patients were before the first cycle of chemotherapy (Tbase) and immediately after intravenous application of the chemotherapy (T1). Healthy subjects were measured once without any further intervention. Measurements were conducted using an individually manufactured system consisting of a handheld probe and a wavelength‐tunable diode laser‐based 488 nm SHG light source. Hereby, changes in both skin fluorescence and shifted excitation resonance Raman difference spectroscopy (SERRDS) carotenoid signals were assessed. Results Healthy subjects showed significantly (P < .001) higher mean concentrations of carotenoids compared to cancer subjects at Tbase. An increase in fluorescence intensity was detected in almost all patients after chemotherapy, especially after doxorubicin infusion. Furthermore, a decrease in the carotenoid concentration in the skin after chemotherapy was found. Conclusion The SERRDS based noninvasive detection can be used as an indirect quantitative assessment of fluorescent chemotherapeutics. The lower carotenoid SERRDS intensities at Tbase might be due to cancerous diseases and co‐medication.

Carotenoids in Human Skin In Vivo: Antioxidant and Photo-Protectant Role against External and Internal Stressors

“…In a pilot study of 20 patients that were suffering from various cancers, it was shown that the concentration of carotenoids in the SC of patients that were measured before chemotherapy was significantly lower than that of healthy individuals ( p < 0.001) [ 219 ], probably due to the psychological burden and anxiety that cancer patients suffered from or the accumulating long-lasting effect of previous chemotherapy cycles [ 220 ]. Although the concentration of carotenoids in the SC does not correlate with the age of a healthy person [ 192 ], such a correlation has been found for the skin of patients suffering from cancer, which was decreasing with increasing patient age [ 221 ].…”

“…The fluorescent signal of doxorubicine could be detected 1–2 h after starting the intravenous infusion and remained there for at least 4.5 h [ 223 ] until it disappeared. Other non-fluorescent drugs, such as paclitaxel, 5-fluorouracil, and folinic acid, despite the presence of specific Raman bands [ 224 ], could not be detected on the skin surface in vivo by CRM, which may be due to their chemical properties, low concentration, and/or metabolism [ 219 ]. Before the invention of targeted therapies and immune therapy, many common chemotherapeutic agents were based on or caused radical formation, e.g., cytostatics inducing in particular ROS, increasing the amount of oxidation products in the body [ 225 , 226 ].…”

“…A chemotherapy including intravenous infusion of paclitaxel (175 mg/m 2 every 3-weeks), docetaxel (30–35 mg/m 2 every 3-weeks), or 5-fluorouracil (2400 mg/m 2 every 2-weeks), leads to a decrease ( p < 0.05) of the carotenoid concentration in the palm immediately after a single infusion by approximately 5, 12, and 7% on average, respectively, which is an indirect indicator of increased oxidative processes [ 221 ]. At the same time, the effect of non-fluorescent chemotherapeutic drugs on the palm was detected not only by a decrease in the carotenoid concentration, but also by an increase in the fluorescence intensity of the SC after the drug infusion [ 219 ], which can be explained by the oxidation of SC components caused by the action of the chemotherapeutic drug. This explanation is confirmed by recent studies [ 112 , 113 ], showing that the increase in the fluorescence intensity may be due to an increase in the concentration of oxidation products, such as proteins, lipids, amino acids, and DNA.…”

“…Thus, it has been shown, directly and indirectly, that systemically applied chemotherapeutic agents can reach the skin surface as part of the sweat, where they re-penetrate into the SC, interacting with its components, and reducing the carotenoid concentration [ 219 , 221 ].…”

Versatile turnkey laser system operating multi-section diode lasers and diode laser systems in the VIS and NIR spectral range

“…17). Also, here results from measurements in the frame of a clinical study [14,15] and a nutrition study were published [16]. The necessary software for system control, data management, and data analysis was developed by FBH.…”