Maternal-fetal in vivo imaging: A combined PET and MRI study

Helene Benveniste, Joanna S. Fowler, William D. Rooney, Daryn H. Moller, W. Walter Backus, Donald A. Warner, Pauline Carter, Payton King, Bruce Scharf, David A. Alexoff, Yeming Ma, Paul Vaska, David Schlyer, Nora D. Volkow

Research output: Contribution to journalArticle

48 Scopus citations

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 18F-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 μg/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 18F-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 18F-FDG readily crosses the placenta and that 18F 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1522-1530
Number of pages9
JournalJournal of Nuclear Medicine
Volume44
Issue number9
StatePublished - Sep 1 2003

Keywords

  • Imaging
  • In vivo
  • Maternal-fetal exchange
  • Primate

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Benveniste, H., Fowler, J. S., Rooney, W. D., Moller, D. H., Backus, W. W., Warner, D. A., Carter, P., King, P., Scharf, B., Alexoff, D. A., Ma, Y., Vaska, P., Schlyer, D., & Volkow, N. D. (2003). Maternal-fetal in vivo imaging: A combined PET and MRI study. Journal of Nuclear Medicine, 44(9), 1522-1530.