Nuclear Imaging of Bacterial Infection: The State of the Art and Future Directions

Abstract

Increased mortality rates from infectious diseases is a growing public health concern. Successful management of acute bacterial infections requires early diagnosis and treatment, which are not always easy to achieve. Structural imaging techniques such as CT and MRI are often applied to this problem. However, these methods generally rely on secondary inflammatory changes and are frequently not specific to infection. The use of nuclear medicine techniques can add crucial complementary information, allowing visualization of infectious pathophysiology beyond morphologic imaging. This review will discuss the current structural and functional imaging techniques used for the diagnosis of bacterial infection and their roles in different clinical scenarios. We will also present several new radiotracers in development, with an emphasis on probes targeting bacteria-specific metabolism. As highlighted by the current coronavirus disease 2019 epidemic, caused by the novel severe acute respiratory syndrome coronavirus 2, similar thinking may apply in imaging viral pathogens; for this case, prominent effects on host proteins, most notably angiotensin-converting enzyme 2, might also provide worthwhile imaging targets.

Keywords: PET; SPECT; imaging; infection; nuclear medicine.

FIGURE 1.

Examples of structural and functional imaging used in diagnosis of infection. (A) Plain radiography of 55-y-old man with diskitis–osteomyelitis after corpectomy. (B and C) CT and MRI of 23-y-old man with chronic diskitis–osteomyelitis. (D) Ultrasound of 4-y-old boy with perforated appendicitis and associated abscess. (E) ^99mTc-methylene diphosphonate bone scan of right ulnar osteomyelitis. (Reprinted with permission of (25).) (F) ¹¹¹In-WBC SPECT/CT of infected right knee arthroplasty. (Reprinted with permission of (25).) (G) ⁶⁷Ga-citrate scan of 61-y-old man with infected endovascular graft of aortic arch. (Reprinted with permission of (74).) (H) ¹⁸F-FDG/PET of 66-y-old man with infected thoracic aorta endograft. (A–D) Red arrowhead indicates point of infection; (E–H) red arrowhead indicates increased tracer uptake.

FIGURE 2.

64-y-old woman with knee replacement and periprosthetic osteomyelitis (red arrowhead) as depicted via plain radiography (A) and radiolabeled ¹¹¹In-leukocyte imaging (B, top row) demonstrates brightest uptake at medial aspect of tibial plateau. ^99mTc-sulfur colloid imaging (B, bottom row) demonstrates no corresponding uptake in region of medial tibial plateau. Therefore, findings are consistent with osteomyelitis.

FIGURE 3.

Examples of ¹⁸F-FDG PET in cardiovascular disease. (A) A 17-y-old boy with non-Hodgkin lymphoma, found to have catheter-associated thrombus consistent with infection, with arrowheads indicating increased FDG uptake in and around catheter. (B) A 59-y-old man with aortic valve prosthesis infection caused by E. faecalis, requiring surgical replacement. Arrowheads indicate increased uptake by valve. CECT = contrast-enhanced CT.

FIGURE 4.

Incidental finding of infection in 65-y-old woman with fallopian tube cancer. (A) Contrast-enhanced CT shows tonsillar abscess (arrowheads). (B and C) Focal increase in uptake on ¹⁸F-FDG PET and ¹⁸F-FDG PET/CT in same location (red arrowhead).

FIGURE 5.

Examples of novel non–sugar-based infection-targeted radiotracers for PET. (A and B) Increased uptake of radiotracers in infection compared with sterile inflammation in 2 rodent models: ¹⁸F-fluoropropyl-trimethoprim (FPTMP) uptake in mice infected with E. coli (arrowhead shows sterile inflammation, arrow shows infection) (A, reprinted with permission of (53)) and ¹⁸F-PABA uptake in rat infected with S. aureus (red arrows show sterile inflammation, yellow arrows show infection) (B, reprinted with permission of (64)). (C) ¹¹C-d-Ala uptake in rat intervertebral disk infected with S. aureus (red arrowheads) and mouse lung infected with P. aeruginosa (red arrowheads). (Reprinted with permission of (73).) (D–F) Chemical structures of ¹⁸F-FPTMP (D), ¹⁸F-PABA (E), and ¹¹C-d-Ala (F). ID = injected dose.

FIGURE 6.

Examples of novel sugar-based infection-targeted radiotracers for PET/CT. (A–C) Increased uptake of radiotracers in infection compared with sterile inflammation in 3 rodent models: ¹⁸F-maltohexaose uptake in rat infected with E. coli (left arrows show infection, right arrows show sterile inflammation) (A, reprinted with permission of (57)), ¹⁸F-fluoromaltotriose uptake in mice infected with E. coli (yellow arrow shows infection site) (B, reprinted with permission of (59)), and 2-deoxy-2-¹⁸F-fluorosorbitol (¹⁸F-FDS) uptake in mice infected with E. coli (yellow arrows show infection, red arrows show sterile inflammation). (C, reprinted with permission of (61)). (D–F) Chemical structures of ¹⁸F-maltohexaose (D), ¹⁸F-fluoromaltotriose (E), and ¹⁸F-FDS (F), obtained from chemical reduction of ¹⁸F-FDG. CFU = colony-forming unit; ID = injected dose.