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| Brain |
| Copyright : Chrischan, Wikipedia commons |
Inflammation occurs in the human brain during illnesses such as
Alzheimer's disease, Parkinson’s disease, stroke and
traumatic brain injury. Now, a research team in Japan has developed
a probe that can bind to the pro-inflammatory enzyme cyclooxygenase
(COX). The probe, 11C-ketoprofen methyl ester, enables researchers
to observe when and where the enzyme is acting in the brains of
living animals using positron emission tomography (PET)
imaging.
In PET imaging, a radioactive tracer that binds specifically to a
specific molecule in the body is injected into a living organism.
Images are then taken with a PET scanner, indicating where in the
body that tracer is found.
Led by Hirotaka Onoe at the RIKEN Center for Molecular Imaging
Science in Kobe, the researchers had previously discovered that
11C-ketoprofen methyl ester could recognize COX, but not which of
its two forms. To determine which isoform is responsible for
binding their molecular probe, Miho Shukuri, a young member of
Onoe’s team, utilized a series of mice lacking the genes for
either COX-1 or COX-2. She found that the PET probe could bind to
the brains of COX-2-deficient mice, but not to those lacking COX-1.
According to the researchers, 11C-ketoprofen methyl ester is
therefore the first PET probe that is specific to COX-1 in living
animals.
When Shukuri injected bacterial antigens into the brain of rats to
induce inflammation, she saw the PET probe build up in the brain
within six hours to one day after antigen injection. The levels
dropped a week later. Because COX-1 is rapidly activated by brain
injury, this may mean that administration of drugs that block COX-1
soon after injury could prevent the progression of brain damage.
“COX-1 could therefore be a promising target for the
neurodegenerative diseases that exhibit neuro-inflammation,”
explains Onoe.
Microglia are immune cells in the brain that proliferate in
response to injury, while macrophages are immune cells normally
found within the blood that invade the brain after injury. The
researchers observed that the injury-induced increase in brain
COX-1 seemed to occur within microglia and macrophages, which also
became more numerous in the brain after exposure to bacterial
antigens. Other research groups have found COX-1-expressing
microglia in diseases such as Alzheimer's disease,
Parkinson’s disease and multiple sclerosis. This suggests to
Onoe and colleagues that 11C-ketoprofen methyl ester could be used
to track the time course and localization of increased COX-1
expression in living organisms, including humans, suffering from
diseases linked to neuro-inflammation.
Reference:
1. Shukuri, M., Takashima-Hirano, M., Tokuda, K., Takashima, T.,
Matsumura, K., Inoue, O., Doi, H., Suzuki, M., Watanabe, Y. &
Onoe, H. In vivo expression of cyclooxygenase-1 in activated
microglia and macrophages during neuroinflammation visualized by
PET with 11C-ketoprofen methyl ester. The Journal of Nuclear
Medicine published online 1 July, 2011 (doi:
10.2967/jnumed.110.084046).
2. Takashima-Hirano, M., Shukuri, M., Takashima, T., Goto, M.,
Wada, Y., Watanabe, Y., Onoe, H., Doi, H. & Suzuki, M. General
method for the 11C-labeling of 2-arylpropionic acids and their
esters: construction of a PET tracer library for a study of
biological events involved in COXs expression. Chemistry 16,
4250–4258 (2010).
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