Assessment of the exhalation kinetics of volatile cancer biomarkers based on their physicochemical properties

Abstract

The current review provides an assessment of the exhalation kinetics of volatile organic compounds (VOCs) that have been linked with cancer. Towards this end, we evaluate various physicochemical properties, such as 'breath:air' and 'blood:fat' partition coefficients, of 112 VOCs that have been suggested over the past decade as potential markers of cancer. With these data, we show that the cancer VOC concentrations in the blood and in the fat span over 12 and 8 orders of magnitude, respectively, in order to provide a specific counterpart concentration in the exhaled breath (e.g., 1 ppb). This finding suggests that these 112 different compounds have different storage compartments in the body and that their exhalation kinetics depends on one or a combination of the following factors: (i) the VOC concentrations in different parts of the body; (ii) the VOC synthesis and metabolism rates; (iii) the partition coefficients between tissue(s), blood and air; and (iv) the VOCs' diffusion constants. Based on this analysis, we discuss how this knowledge allows modeling and simulating the behavior of a specific VOC under different sampling protocols (with and without exertion of effort). We end this review by a brief discussion on the potential role of these scenarios in screening and therapeutic monitoring of cancer.

Figure 1

Output of isoprene (nmol min⁻¹), acetone (arbitrary units) and CO₂ (L min⁻¹) for a healthy volunteer during rest phases and exertion of an effort of 75 W on a stationary bicycle. In case of CO₂, 15 exhalations per minute with 3 L of alveolar air with 4% of CO₂ correspond to 1.8 L min⁻¹ of CO₂ ( = 15*3*0.04 L min⁻¹). Isoprene output through exhaled breath may increase up to a factor ~10 during exertion of an effort, whereas the concentration in breath increases up to a factor ~5. In this experiment, two steady-states of isoprene exhalation appear, (A) at ~25 nmol min⁻¹ (corresponding to production of isoprene in the liver) and (B) at ~100 nmol L⁻¹ (corresponding to production of isoprene in the muscles). In a person with high cholesterol blood level, the production of isoprene in the liver would be decreased under the influence of statins [139]. Reproduced with permission from [69], © 2009 IOP Publishing.

Figure 2

Partition coefficient, –log(λ_b:a), for 112 volatile cancer biomarkers published during the last decade [, , , –121], as well as acetone and 2-pentanone for comparison. The color for the different compound names is chosen according to the chemical class. Compounds with a higher log(λ_b:a) will tend to be in the blood and vice versa.

Figure 3

Partition coefficient, –log(λ_f:b), for 112 volatile cancer biomarkers published during the last decade [, , , –121], as well as acetone and 2-pentanone for comparison. The color for the different compound names is chosen according to the chemical class. Compounds with a higher log(λ_f:b) will tend to be in the fat and vice versa.