Spatiotemporal measurement of free radical elimination in the abdomen using an in vivo ESR-CT imaging system.
Electron spin resonance (ESR) imaging can visualize the distribution of free radicals in living systems according to their concentrations. However, the application of ESR imaging to living animals has not been well established. Using a rapid field scan L-band ESR imaging system, we have successfully obtained two-dimensional ESR projection (xz-plane projection) and three-dimensional ESR-CT (trans-axial section along the y-axis) images of the abdomen of living mice after an injection of 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) into the tail vein. The in vivo two-dimensional ESR projection imaging clearly visualized the carbamoyl-PROXYL distribution and the rapid decay process in the abdomen. Because among the viscera, the liver is most abundantly associated with a blood volume, the outline of the image can be composed mainly of this organ. We therefore attempted to find whether there will be a difference in spatiotemporal dynamics of carbamoyl-PROXYL in the abdomens between the control and the mice with liver damage by two-dimensional ESR projection. In the control mice, carbamoyl-PROXYL was almost completely eliminated from the abdomen within 5 minutes after administration. On the other hand, in mice with carbon tetrachloride-damaged livers, the decay of carbamoyl-PROXYL was markedly prolonged. Even at 5 min after administration, carbamoyl-PROXYL remained clearly visible in the abdomen. In vivo three-dimensional ESR-CT imaging showed an even distribution of carbamoyl-PROXYL throughout the whole liver, which corresponded well with the images of trans-axial sections of the murine abdomen. We have succeeded in displaying two-dimensional ESR projection and three-dimensional ESR-CT images of carbamoyl-PROXYL distribution and clearance in the abdomen of a living animal. The ESR-CT imaging technique is considered to be a powerful new tool for noninvasive investigations of the in vivo spatiotemporal dynamics of free radical distribution and elimination in the organs.
Togashi
H
H
The Second Department of Internal Medicine, Yamagata University School of Medicine, Iida-Nishi, Japan. htogashi@yamagata-u.ac.jp
Shinzawa
H
H
Ogata
T
T
Matsuo
T
T
Ohno
S
S
Saito
K
K
Yamada
N
N
Yokoyama
H
H
Noda
H
H
Oikawa
K
K
Kamada
H
H
Takahashi
T
T
D000005:Abdomen; D000818:Animals; D003497:Cyclic N-Oxides / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy / Q000295:instrumentation / Q000379:methods; D005609:Free Radicals / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation* / Q000379:methods; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011759:Pyrrolidines / Q000493:pharmacokinetics; D013997:Time Factors; D014057:Tomography, X-Ray Computed
D003497:Cyclic N-Oxides; D005609:Free Radicals; D011759:Pyrrolidines; C077426:3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl