Maternal-fetal in vivo imaging: a combined PET and MRI study.
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.
Benveniste
Helene
H
Medical Department, Brookhaven National Laboratory, Upton, New York 11793, USA. benveniste@bnl.gov
Fowler
Joanna S
JS
Rooney
William D
WD
Moller
Daryn H
DH
Backus
W Walter
WW
Warner
Donald A
DA
Carter
Pauline
P
King
Payton
P
Scharf
Bruce
B
Alexoff
David A
DA
Ma
Yeming
Y
Vaska
Paul
P
Schlyer
David
D
Volkow
Nora D
ND
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*
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18