title: Direct, quantitative, and noninvasive imaging of the transport of active agents through intact brain with positron emission tomography.
abstract: OBJECTIVE
  Our goal was to use positron emission tomography (PET) to analyze the movement of radiolabeled agents in tissue to enable direct measurement of drug delivery to the brain.
  
  
  METHODS
  Various (11)C- and (18) F-labeled compounds were delivered directly to an agarose phantom or rat striatum. Concentration profiles were extracted for analysis and fitted to diffusion models.
  
  
  RESULTS
  Diffusion coefficients ranged from 0.075 ± 0.0026 mm(2)/min ([(18) F]fluoride ion, 18 Da) to 0.0016 ± 0.0018 mm(2)/min ([(18) F]NPB4-avidin, 68 kDa) and matched well with predictions based on molecular weight (R (2) = 0.965). The tortuosity of the brain extracellular space was estimated to be 1.56, with the tissue clearance halftime of each tracer in the brain varying from 19 to 41 min.
  
  
  CONCLUSIONS
  PET is an effective modality to directly quantify the movement of locally delivered drugs or drug carriers. This continuous, noninvasive assessment of delivery will aid the design of better drug delivery methods.
authors.affiliation: Diagnostic Radiology, Yale School of Medicine, New Haven, CT, 06511, USA, rachael.sirianni@dignityhealth.org.
authors.forename: Rachael W
authors.initials: RW
authors.lastname: Sirianni
authors.forename: Ming-Qiang
authors.initials: MQ
authors.lastname: Zheng
authors.forename: W Mark
authors.initials: WM
authors.lastname: Saltzman
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Huang
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
mesh_terms: D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000000981:diagnostic imaging*; D004058:Diffusion; D008297:Male; D008970:Molecular Weight; D017072:Neostriatum / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012685:Sepharose; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; D012685:Sepharose