Is Imaging Bacteria with PET a Realistic Option or an Illusion?

Abstract

The application of [18F]-fluorodeoxyglucose ([18F]FDG) as a radiotracer to detect sites of inflammation (either due to bacterial infection or primary inflammation) has led to exploring the role of PET in visualizing bacteria directly at sites of infection. However, the results from such efforts are controversial and inconclusive so far. We aimed to assess the limitations of PET as an effective modality in the diagnosis of bacterial infections. Inflammation due to bacterial infections can be visualized by using [18F]FDG-PET. However, the non-specificity of [18F]FDG makes it undesirable to visualize bacteria as the underlying cause of inflammation. Hence, more specific radiotracers that possibly bind to or accumulate in bacteria-specific receptors or enzymes are being explored. Several radiotracers, including 2-deoxy-2-[18F]fluorosorbitol ([18F]FDS), 6-[18F]-fluoromaltose, [11C]para-aminobenzoic acid ([11C]PABA), radiolabeled trimethoprim (11C-TMP) and its analog fluoropropyl-trimethoprim (18F-FPTMP), other radiolabeled sugars, and antimicrobial drugs have been used to image microorganisms. Unfortunately, no progress has been made in translating the results to routine human use; feasibility and other factors have constrained their success in clinical settings. In the current article, we discuss the limitations of direct bacterial visualization with PET tracers, but emphasize the important role of [18F]FDG-PET as the only option for detecting evidence of infection.

PET/CT Imaging of Infectious Diseases: Overview of Novel Radiopharmaceuticals

“…As bacterial imaging probes, proposed 11 C-labeled tracers can present a higher specificity intrinsically linked to the molecular pathways of D-11 C-Met, 11 C-PABA, and 11 C-TMP. They could improve the detection of infectious foci, allowing the visualization of bacteria directly at sites of infection [104].…”

“…As bacteria-specific imaging probes, both of these tracers are under study for their affinity for key enzymes in the folate synthesis pathway, in preclinical models and in humans [62]. Despite the promising role of all antibiotic tracers, limited success has been registered for 18 F-FPTMP during the last decade, mainly due to limitations of PET spatial resolution in the detection of bacterial infections [104].…”

Infection Imaging: Focus on New Tracers?

“…Besides the general disadvantages of radiolabeled antibiotics mentioned before, this approach faces tracer-specific disadvantages. Preclinical evaluation has revealed nonspecific absorption in the presence of an excess of unlabeled substance and minimal binding to heat-inactivated bacteria, raising concerns about its specificity (42,44). Therefore, we believe that there are more promising candidates for clinical translation in imaging infection.…”

“…This capability is of special interest in imaging infections (e.g., in the postoperative setting in PVIE, CDRIE, and VGEI) because of unspecific leakage of tracers due to the increased vascular endothelial permeability that occurs in infection and inflammation. Most first-in-humans studies of novel tracer candidates in a small number of patients do not distinguish between the 2 components of the signal-active binding and vascular leakage-but positive results are misinterpreted as active binding (44).…”