Retained products of conception (RPOC) are a common and treatable complication after delivery or termination of pregnancy. The pathologic diagnosis of RPOC is made based on the presence of chorionic villi, which indicates persistent placental or trophoblastic tissue. In the setting of postpartum hemorrhage, however, distinguishing RPOC from bleeding related to normal postpartum lochia or uterine atony can be clinically challenging. Ultrasonographic (US) evaluation can be particularly helpful in these patients, and a thickened endometrial echo complex (EEC) or a discrete mass in the uterine cavity is a helpful gray-scale US finding that suggests RPOC. However, gray-scale US findings alone are inadequate for accurate diagnosis. Detection of vascularity in a thickened EEC or an endometrial mass at color or power Doppler US increases the positive predictive value for the diagnosis of RPOC. Computed tomography or magnetic resonance imaging may be helpful when US findings are equivocal and typically demonstrates an enhancing intracavitary mass in patients with RPOC. Diagnostic pitfalls are rare but may include highly vascular RPOC, which can be mistaken for a uterine arteriovenous malformation; true arteriovenous malformations of the uterus; invasive moles; blood clot; and subinvolution of the placental implantation site.

Molecular imaging could fulfill unmet clinical needs for diagnosing and monitoring bacterial infections, if translational barriers are addressed.

There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [¹⁸F]fluoropropyl-trimethoprim, or [¹⁸F]FPTMP, shows a greater than 100-fold increased uptake in vitro in live bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) relative to controls. In a rodent myositis model, [¹⁸F]FPTMP identified live bacterial infection without demonstrating confounding increased signal in the same animal from other etiologies including chemical inflammation (turpentine) and cancer (breast carcinoma). Additionally, the biodistribution of [¹⁸F]FPTMP in a nonhuman primate shows low background in many important tissues that may be sites of infection such as the lungs and soft tissues. These results suggest that [¹⁸F]FPTMP could be a broadly useful agent for the sensitive and specific imaging of bacterial infection with strong translational potential. Significance The ability to distinguish bacterial infection from other pathologies in humans can be challenging. An imaging agent with great sensitivity and spatial resolution that would allow noninvasive identification of sites of bacterial infection could increase our understanding of the natural history of bacterial infection in patients and potentially be used to support clinical decision making. Here, we report the first synthesis of a fluorine-18–labeled derivative of the antibiotic trimethoprim for positron emission tomography imaging and show that it can identify bacterial infection in rodents. Importantly, this radiotracer does not accumulate at sites of sterile inflammation or cancer, pathologies that often have overlapping imaging features with bacterial infection.

Cell-based therapeutics have considerable promise across diverse medical specialties; however, reliable human imaging of the distribution and trafficking of genetically engineered cells remains a challenge. We developed positron emission tomography (PET) probes based on the small-molecule antibiotic trimethoprim (TMP) that can be used to image the expression of the Escherichia coli dihydrofolate reductase enzyme (eDHFR) and tested the ability of [¹⁸F]-TMP, a fluorine-18 probe, to image primary human chimeric antigen receptor (CAR) T cells expressing the PET reporter gene eDHFR, yellow fluorescent protein (YFP), and Renilla luciferase (rLuc). Engineered T cells showed an approximately 50-fold increased bioluminescent imaging signal and 10-fold increased [¹⁸F]-TMP uptake compared to controls in vitro. eDHFR-expressing anti-GD2 CAR T cells were then injected into mice bearing control GD2^- and GD2⁺ tumors. PET/computed tomography (CT) images acquired on days 7 and 13 demonstrated early residency of CAR T cells in the spleen followed by on-target redistribution to the GD2⁺ tumors. This was corroborated by autoradiography and anti-human CD8 immunohistochemistry. We found a high sensitivity of detection for identifying tumor-infiltrating CD8 CAR T cells, ∼11,000 cells per mm³. These data suggest that the [¹⁸F]-TMP/eDHFR PET pair offers important advantages that could better allow investigators to monitor immune cell trafficking to tumors in patients.