A novel method for tracking nitrogen kinetics in vivo and ex vivo using radioactive nitrogen-13 gas and Positron Emission Tomography

RationaleDecompression sickness (DCS) is caused by gaseous nitrogen dissolved in tissues forming bubbles during decompression. To date no method exists to identify nitrogen within tissues, but with advances in PET technology it may be possible to track gaseous radionuclides into tissues. We aimed to develop a method to track nitrogen movement in vivo that could then be used to further our understanding of DCS using nitrogen-13 (13N2) - a radioactive isotope of nitrogen that emits {beta}+ radiation. MethodsA single anesthetized and ventilated Sprague Dawley rat lay supine inside a PET scanner for 30 min. The rat breathed oxygen for the first 2 min, then was switched to a bag containing 13N2 gas mixed with oxygen for 20 min, then breathed oxygen alone for the final 8 min. Gas samples were drawn from the inspiratory line at 5, 15 and 25 min. The PET scanner recorded 13N2 with energy windows of 250-750 keV. Following the scan, a mixed blood sample was taken from the heart, while the brain, liver, femur and thigh muscle were removed to determine organ radioactivity using a gamma counter. ResultsThe gas samples at 5 (5.7 kbq.ml-1) and 15 min (5.3 kbq.ml-1) showed radioactivity in the inspired gas that was absent at 25 min (0.1 kbq.ml-1), when the 13N2 was stopped. The signal intensity in the PET scanner increased from baseline (0.03) to 2-12 min (0.68{+/-}0.31), and 12-22 min (0.88{+/-}0.06), before reducing slightly from 22-30 min (0.61{+/-}0.04). All organs had radioactivity when measured in the gamma counter, with the highest counts in the liver (12593 counts.min-1.g-1) and the lowest in the muscle (2687 counts.min-1.g-1). Principal ConclusionsThis study successfully demonstrated a quantitative 3D imaging method of tracking nitrogen gas through the body both in vivo and ex vivo using PET.