Preclinical PET imaging of the developing fetus during pregnancy: Current state and future potential

During pregnancy, the fetus is subject to complex interactions of biological and environmental factors that can influence developmental trajectories even into adulthood. Although several factors, such as maternal malnutrition and substance abuse, have been associated with offspring development, the mechanisms through which short- and long-term effects manifest in the fetus are not well understood. To this end, positron emission tomography (PET) imaging using preclinical models has been a promising and underutilized technique for investigating fetal exposure and physiology in utero with minimal invasiveness. Herein, we review the application of PET imaging to fetal medicine and survey the limitations and opportunities for future longitudinal studies of development. Over the past two decades, several studies have utilized preclinical PET in quantitative studies of maternal-fetal exchange dynamics of pharmaceuticals, environmental toxins, or drugs of abuse. Another application has shown [¹⁸F]FDG PET to be a potential biomarker for fetal glucose transport, hypoxia, and brain function in utero. In contrast, only a few studies have employed reversibly binding radioligands to quantify protein markers of dopaminergic signaling and synaptic density in the fetal brain. As PET technology continues to improve, our review highlights a future role for PET in longitudinal studies of fetal health and development.