title: Comparison of radiolabeled isatin analogs for imaging apoptosis with positron emission tomography.
abstract: BACKGROUND
  Caspase-3 is one of the executioner caspases activated as a result of apoptosis. Radiolabeled isatins bind to caspase-3 with high affinity and are potential tracers for use with positron emission tomography to image apoptosis. We compared the ability of two novel radiolabeled isatins, [18F]WC-IV-3 and [11C]WC-98, to detect caspase-3 activation in a rat model of cycloheximide-induced liver injury.
  
  
  METHODS
  Male Sprague-Dawley rats were treated with cycloheximide and then imaged with microPET 3 h later with [18F]WC-IV-3 and [11C]WC-98. Biodistribution studies were also performed simultaneously, with caspase-3 activation verified by fluorometric enzyme assay and Western blots.
  
  
  RESULTS
  MicroPET imaging studies demonstrated similar behavior of both tracers but with a lower maximum peak with [11C]WC-98 than with [18F]WC-IV-3. Biodistribution studies demonstrated increased uptake of both tracers in the liver and spleen, but this was statistically significant only in the liver with both compounds. The level of [18F]WC-IV-3 uptake appeared to correlate roughly with rates of caspase-3 activation by the enzyme assay, but the magnitude of difference between treated and control groups was lower than that observed in previously published data with [18F]WC-II-89, another radiolabeled isatin analog. Activation was also confirmed in the liver and spleen but not in fat by Western blot.
  
  
  CONCLUSIONS
  [18F]WC-IV-3 uptake appears to correlate with increased caspase-3 enzyme activity, but the dynamic range of uptake of these two tracers appears to be less than that seen with [18F]WC-II-89. Studies are ongoing to verify these results in other animal models of apoptosis.
authors: Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Delphine L
authors: DL
authors: Chen
authors: Dong
authors: D
authors: Zhou
authors: Wenhua
authors: W
authors: Chu
authors: Phillip E
authors: PE
authors: Herrbrich
authors: Lynne A
authors: LA
authors: Jones
authors: Justin M
authors: JM
authors: Rothfuss
authors: Jacquelyn T
authors: JT
authors: Engle
authors: Marco
authors: M
authors: Geraci
authors: Michael J
authors: MJ
authors: Welch
authors: Robert H
authors: RH
authors: Mach
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D007510:Isatin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D007553:Isotope Labeling; D008099:Liver / Q000000981:diagnostic imaging / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D008297:Male; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D061945:Caspase Inhibitors; D011759:Pyrrolidines; D007510:Isatin; D003513:Cycloheximide; D053148:Caspase 3; C032519:pyrrolidine