Breath markers for therapeutic radiation

Abstract

Radiation dose is important in radiotherapy. Too little, and the treatment is not effective, too much causes radiation toxicity. A biochemical measurement of the effect of radiotherapy would be useful in personalisation of this treatment. This study evaluated changes in exhaled breath volatile organic compounds (VOC) associated with radiotherapy with thermal desorption gas chromatography mass-spectrometry followed by data processing and multivariate statistical analysis. Further the feasibility of adopting gas chromatography ion mobility spectrometry for radiotherapy point-of-care breath was assessed. A total of 62 participants provided 240 end-tidal 1 dm3 breath samples before radiotherapy and at 1, 3, and 6 h post-exposure, that were analysed by thermal-desorption/gas-chromatography/quadrupole mass-spectrometry. Data were registered by retention-index and mass-spectra before multivariate statistical analyses identified candidate markers.A panel of sulfur containing compounds (thio-VOC) were observed to increase in concentration over the 6 h following irradiation. 3-methylthiophene (80 ng.m−3 to 790 ng.m−3) had the lowest abundance while 2-thiophenecarbaldehyde(380 ng.m−3 to 3.85 μg.m−3) the highest; note, exhaled 2-thiophenecarbaldehyde has not been observed previously. The putative tumour metabolite 2,4-dimethyl-1-heptene concentration reduced by an average of 73% over the same time. Statistical scoring based on the signal intensities thio-VOC and 3-methylthiophene appears to reflect individuals’ responses to radiation exposure from radiotherapy. The thio-VOC are hypothesised to derive from glutathione and Maillard-based reactions and these are of interest as they are associated with radio-sensitivity. Further studies with continuous monitoring are needed to define the development of the breath biochemistry response to irradiation and to determine the optimum time to monitor breath for radiotherapy markers. Consequently, a single 0.5 cm3 breath-sample gas chromatography-ion mobility approach was evaluated. The calibrated limit of detection for 3-methylthiophene was 10 μg.m−3 with a lower limit of the detector’s response estimated to be 210 fg.s−1; the potential for a point-of-care radiation exposure study exists.

Noninvasive detection of soft tissue sarcoma using volatile organic compounds in exhaled breath: a pilot study

“…To minimize the effect of these influencing factors, we matched the STS population with the control group by age and gender, performed all eNose measurements in the same testing area and asked participants to abstain from food, drink and smoking for 3 h before testing. Furthermore, as radiotherapy and chemotherapy cause oxidative stress, inflammation and tissue damage, participants who had a history of receiving these treatments were excluded [29,30]. We did not match patients based on BMI or other influencing factors, such as smoking status and comorbidities, because of the small sample size.…”

Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness

“…Individual hydrocarbons such as 2,4- and 2,2-dimethylpentane, 2- methylbutane, 4-methyldecane, 5-methylnonane and isoprene have been previously reported as predictive for pneumonia and heart failure ( 12 , 15 ). Sulphur-containing VOCs, such as 3-methylthiophene, allyl methyl sulphide and carbonyl sulphide (found to be predictive of COPD) are associated with bacterial metabolism, postulated to originate from the gut ( 16 ) and on occasions as a result of radiation injury ( 17 ); however, 2,3-butanedione, also predictive of COPD, has been identified as a metabolic product of bacterial isolates from patients with cystic fibrosis (CF) ( 16 ) and postulated to be an important metabolite in monitoring lung infection in CF, COPD and pneumonia. We acknowledge that the biological origin of most VOCs within our biomarker signature has yet to be fully elucidated.…”

The variability of volatile organic compounds in the indoor air of clinical environments

“…The approach to quality control has been described previously [22]. Instrumentation performance was continuously monitored by analysing 0.2 µl of a reference mixture containing 20 standards (table S2) daily before analysis (every 4 samples).…”

“…Instrument performance was evaluated by monitoring the Z-scores of: retention time, peak area, height, width, and symmetry for the 20 standards in the reference mixture. Analysis was undertaken when instruments were within Z = ±3 for more than 80% of the 100 quality control parameters [23], [22]. The two internal standards were also monitored to track the combined stability of the TD-GC-MS analysis and dry purging system see figure S2 for comparative examples of data.…”

“…Instrument condition was verified by running system blank desorption profiles before and after every analysis. The blank desorption profiles were also assessed statistically [22], figure S3. These procedures simultaneously screened for possible adsorbent tube conditioning artifacts, adsorbent degradation artefacts, cold-trap and transfer line artefacts, and chromatographic integrity, Further all adsorbent tubes were weighed on a five figure balance after conditioning and discarded if any significant weight change was observed (Indicative of loss of adsorbent, ingress of contaminant or environmental adducts.).…”