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Review
. 2024 May 17;14(10):1043.
doi: 10.3390/diagnostics14101043.

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

Ferdinando F Calabria  1 , Giuliana Guadagnino  2 , Andrea Cimini  3 , Mario Leporace  1
Affiliations
Review

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

Ferdinando F Calabria et al. Diagnostics (Basel). .

Abstract

Infectious diseases represent one of the most common causes of hospital admission worldwide. The diagnostic work-up requires a complex clinical approach, including laboratory data, CT and MRI, other imaging tools, and microbiologic cultures. PET/CT with 18F-FDG can support the clinical diagnosis, allowing visualization of increased glucose metabolism in activated macrophages and monocytes; this tracer presents limits in differentiating between aseptic inflammation and infection. Novel PET radiopharmaceuticals have been developed to overcome these limits; 11C/18F-labeled bacterial agents, several 68Ga-labeled molecules, and white blood cells labeled with 18F-FDG are emerging PET tracers under study, showing interesting preliminary results. The best choice among these tracers can be unclear. This overview aims to discuss the most common diagnostic applications of 18F-FDG PET/CT in infectious diseases and, as a counterpoint, to describe and debate the advantages and peculiarities of the latest PET radiopharmaceuticals in the field of infectious diseases, which will probably improve the diagnosis and prognostic stratification of patients with active infectious diseases.

Keywords: 18F-FDG; 68Ga-citrate; PET/CT; PET/MRI; infection; inflammation; molecular imaging.

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Conflict of interest statement

The authors do not have any conflicts of interest in the manuscript, including financial, consultant, institutional and other relationships that might lead to bias or a conflict of interest.

Figures

Figure 1
Figure 1
Internalization and phosphorylation of 18F-FDG from the bloodstream in cells.
Figure 2
Figure 2
11C radiolabeled PET radiopharmaceuticals and their respective cellular targets in Gram-positive bacteria. DHFR: dihydrofolate reductase; DHF: dihydrofolate; THF: tetrahydrofolate; 11C-PABA: 11C-para-Aminobenzoic acid; D-11C-Met: D-methyl-11C-methionine; 11C-TMP: 11C-trimethoprim.
Figure 3
Figure 3
After intravenous administration, transferrin-bounded 68Ga-citrate circulates in the bloodstream and is transported by the arteries to the site of inflammation by mechanisms of blood flow and increased vascular permeability. The ferric ion-like properties of 68Ga-citrate allow its binding to lactoferrin, released by the apoptotic processes of leukocytes.
Figure 4
Figure 4
68Ga-FAPI reaches the infectious site by the bloodstream and interacts with FAP in fibroblasts of the infectious microenvironment.
Figure 5
Figure 5
The uptake of radiolabeled somatostatin analogues in infection is due to the overexpression of cell surface somatostatin receptors in activated macrophages.
Figure 6
Figure 6
Simplified preparation of 18F-FDG-radiolabeled white blood cells. Venous blood is collected in a heparinized syringe; after plasma separation and centrifugation, 18F-FDG is added to the white blood cell pellet suspension. After incubation, the radiolabeled white blood cell sediment is reconstituted with the patient’s cell-free plasma and intravenously reinjected (18F-FDG: 18F-fluorodeoxyglucose;—WBC: white blood cell).
Figure 7
Figure 7
Mechanism of uptake of 18F-FDG-labeled white blood cells in infectious foci.
See this image and copyright information in PMC

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