title: Maternal-fetal in vivo imaging: a combined PET and MRI study.
abstract: An understanding of how drugs are transferred between mother and fetus during the gestational period is an important medical issue of relevance to both therapeutic drugs and drugs of abuse. Though there are several in vitro and in vivo methods to examine this issue, all have limitations. Furthermore, ethical and safety considerations generally preclude such studies in pregnant humans. PET and appropriately labeled compounds have the ability to provide information on both maternal-fetal drug pharmacokinetics and pharmacodynamics. We present here a nonhuman primate animal model and the methodology for combining PET and MRI to identify fetal organs and to measure maternal and fetal isotope distribution using (18)F-FDG and a whole-body imaging protocol to demonstrate proof-of-principle.
  
  
  METHODS
  One nonpregnant nonhuman primate was used for determination of the anesthesia protocol and MRI methods and 3 pregnant nonhuman primates (Macaques radiata) weighing 4.5-7 kg were used for the imaging study and anesthetized with propofol (160-300 micro g/kg/min). Anatomic T2-weighted MR images were acquired on a 4-T MR instrument. Subsequently, whole-body PET images were acquired 35 min after injection of (18)F-FDG, and standardized uptake values (SUVs) were calculated. Image processing and coregistration were performed using commercial software.
  
  
  RESULTS
  All animals underwent uneventful general anesthesia for a period of up to 7 h. Coregistration of PET and MR images allowed identification of fetal organs and demonstrated that (18)F-FDG readily crosses the placenta and that (18)F accumulates in both maternal and fetal brain, heart, and bladder. Brain SUVs averaged 1.95 +/- 0.08 (mean +/- SD) and 1.58 +/- 0.11 for mothers and fetuses, respectively. Monkeys delivered healthy babies after a normal gestational term of 170 d following the PET/MRI study.
  
  
  CONCLUSIONS
  The pregnant macaque in combination with PET and MRI technology allows the measurement of radioisotope distribution in maternal and fetal organs. This demonstrates the potential for noninvasively measuring the transfer of drugs across the placenta and for measuring the fetal drug distribution. It also opens up the possibility for studying binding and elimination as well as the effects of a drug on specific cellular elements and physiologic processes during the gestational period in a primate model.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, New York 11793, USA. benveniste@bnl.gov
authors.forename: Helene
authors.initials: H
authors.lastname: Benveniste
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: William D
authors.initials: WD
authors.lastname: Rooney
authors.forename: Daryn H
authors.initials: DH
authors.lastname: Moller
authors.forename: W Walter
authors.initials: WW
authors.lastname: Backus
authors.forename: Donald A
authors.initials: DA
authors.lastname: Warner
authors.forename: Pauline
authors.initials: P
authors.lastname: Carter
authors.forename: Payton
authors.initials: P
authors.lastname: King
authors.forename: Bruce
authors.initials: B
authors.lastname: Scharf
authors.forename: David A
authors.initials: DA
authors.lastname: Alexoff
authors.forename: Yeming
authors.initials: Y
authors.lastname: Ma
authors.forename: Paul
authors.initials: P
authors.lastname: Vaska
authors.forename: David
authors.initials: D
authors.lastname: Schlyer
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000818:Animals; D005240:Feasibility Studies; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008255:Macaca radiata; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008431:Maternal-Fetal Exchange; D009928:Organ Specificity; D010920:Placenta / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism*; D011247:Pregnancy; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013382:Subtraction Technique; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18