Rapid intracerebroventricular delivery of 64Cu-DOTA-etanercept after peripheral administration demonstrated by PET imaging
Edward L Tobinick, Kai Chen and Xiaoyuan Chen
BMC Research Notes 2009, 2:28
Published: 27 February 2009
Abstract
Background
The cytokines interleukin-1 and tumor necrosis factor (TNF), and the
cytokine blocker interleukin-1 receptor antagonist, all have been
demonstrated to enter the cerebrospinal fluid (CSF) following
peripheral administration. Recent reports of rapid clinical improvement
in patients with Alzheimer's disease and related forms of dementia
following perispinal administration of etanercept, a TNF antagonist,
suggest that etanercept also has the ability to reach the brain CSF. To
investigate, etanercept was labeled with a positron emitter to enable
visualization of its intracranial distribution following peripheral
administration by PET in an animal model.
Findings
Radiolabeling of etanercept with the PET emitter 64Cu was performed
by DOTA (1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid)
conjugation of etanercept, followed by column purification and 64Cu
labeling. MicroPET imaging revealed accumulation of
64Cu-DOTA-etanercept within the lateral and third cerebral ventricles
within minutes of peripheral perispinal administration in a normal rat
anesthesized with isoflurane anesthesia, with concentration within the
choroid plexus and into the CSF.
Conclusions
Synthesis of 64Cu-DOTA-etanercept enabled visualization of its
intracranial distribution by microPET imaging. MicroPET imaging
documented rapid accumulation of 64Cu-DOTA-etanercept within the
choroid plexus and the cerebrospinal fluid within the cerebral
ventricles of a living rat after peripheral administration. Further
study of the effects of etanercept and TNF at the level of the choroid
plexus may yield valuable insights into the pathogenesis of Alzheimer's
disease.
Read the abstract and full article at Biomed Central Research Notes
