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

Abstract

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.

Keywords: PET; brain function; fetal imaging; in utero; prenatal.

Figure 1.

Fetal imaging papers. (a) The distribution of species used across the papers reviewed. (b) A histogram displaying all fetal pet papers from 1980–2020, in 5-year bins and (c) The distribution of tracers used across the fetal PET imaging studies. Note that some studies employed multiple tracers. Any tracer used only once was categorized as “other”.

Figure 2.

Pregnant rat imaging diagram. The arrangement of fetuses in a maternal rat pregnant with 8 offspring equally distributed between the two uterine horns is depicted. In this review, numerous routes of radiotracer administration in rodents are discussed, and these routes are shown here in yellow.

Figure 3.

Pregnant rat at E21 imaged with microPET/CT. [¹⁸F]FDG PET images summed from 0–90 min and fused with microCT images. Whole-body pregnant rat (right) fused with microCT acquired at 200 µm³ resolution. Representative fetus-placenta unit (left) resliced and shown with microCT alone (106 µm³ resolution) and fused PET with micro-CT. Note that the fetal spine and the ossified portions of the fetal skull are readily visible from the microCT image. MB: maternal brain; MH: maternal heart; MB1: maternal bladder; FPU: fetus-placenta unit.