Investigation of 6-[¹⁸F]-fluoromaltose as a novel PET tracer for imaging bacterial infection - PubMed (original) (raw)

Investigation of 6-[¹⁸F]-fluoromaltose as a novel PET tracer for imaging bacterial infection

Gayatri Gowrishankar et al. PLoS One. 2014.

Abstract

Despite advances in the field of nuclear medicine, the imaging of bacterial infections has remained a challenge. The existing reagents suffer from poor sensitivity and specificity. In this study we investigate the potential of a novel PET (positron emission tomography) tracer that overcomes these limitations.

Methods: 6-[¹⁸F]-fluoromaltose was synthesized. Its behavior in vitro was evaluated in bacterial and mammalian cultures. Detailed pharmacokinetic and biodistribution profiles for the tracer were obtained from a murine model.

Results: 6-[¹⁸F]-fluoromaltose is taken up by multiple strains of pathogenic bacteria. It is not taken up by mammalian cancer cell lines. 6-[¹⁸F]-fluoromaltose is retained in infected muscles in a murine model of bacterial myositis. It does not accumulate in inflamed tissue.

Conclusion: We have shown that 6-[¹⁸F]-fluoromaltose can be used to image bacterial infection in vivo with high specificity. We believe that this class of agents will have a significant impact on the clinical management of patients.

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Conflict of interest statement

Competing Interests: The authors have a patent on the imaging probe described in the manuscript. Patent title: PROBES AND METHODS OF IMAGING A BACTERIAL INFECTION. Serial No. 14/204,402. Filed: March 11, 2014. Docket No. 221907-1950. One of the authors, Dr. Erwan Jouannot, is an employee of Sanofi Inc. This does not alter the authors' adherence to PLOS ONE editorial policies and criteria. Sanjiv Sam Gambhir is on the editorial board for PLOS ONE. This does not alter the authors' adherence to PLOS ONE editorial policies and criteria.

Figures

Figure 1

Figure 1. In vitro characterization of 6-[18F]-fluoromaltose.

A) Uptake of 6-[18F]-fluoromaltose in the indicated strains of bacteria for 60 minutes. B) 1 hour uptake of 6-[18F]-fluoromaltose in the mammalian cell lines, MDA MB231 and HeLa and its uptake in E.coli in the presence of 1 mM maltose. C) Bioluminescence imaging of a macrophage cell line J774 infected with a bioluminescent strain of Listeria monocytogenes. D) 1 hour uptake of 6-[18F]-fluoromaltose in the bioluminescent strain of Listeria monocytogenes and in macrophage cell line J774 with and without intracellular Listeria infections.

Figure 2

Figure 2. In vivo characterization of 6-[18F]-fluoromaltose.

A) 3D color map from a PET/CT scan of a mouse bearing E.coli induced infection on the left thigh (red arrow) 1 hr after tail-vein injection of 7.4MBq of 6-[18F]-fluoromaltose. B) Region of interest analysis (ROIs) from PET/CT images at the indicated time points (n = 4 for each time point) * indicates statistical significance with p<0.05. C) Time activity curve showing accumulation of 6-[18F]-fluoromaltose in the infected muscle (n = 3).

Figure 3

Figure 3. Specificity of 6-[18F]-fluoromaltose for viable bacteria.

A) A coronal slice from a PET/CT image of a mouse bearing 108 CFU of viable bioluminescent E.coli on the right thigh (red arrow) and 108 CFU of heat-inactivated E.coli on the left thigh, 1hr after tail-vein injection of 7.4MBq of 6-[18F]-fluoromaltose B) A transverse slice from the same mouse shown in A), with arrows indicating sites of viable and heat inactivated bacteria. C) Bioluminescent image of the mouse shown in A). D) ROI analysis from PET/CT scan of mice (n = 3). * indicates statistical significance.

Figure 4

Figure 4. Uptake of 6-[18F]-fluoromaltose in infection versus inflammation.

A) Ex-vivo biodistribution of 6-[18F]-fluoromaltose in mice bearing E.coli induced myositis, 2 h and 4 h after tail-vein injection of 7.4MBq of tracer. B) Ex-vivo biodistribution of 6-[18F]-fluoromaltose in mice bearing turpentine oil induced sterile abscess, 2 h after tail-vein injection of 7.4MBq of tracer. C) Representative gram stained muscle sections with a black arrow indicating presence of E.coli in the infected muscle section. D) Representative H&E stained muscle sections showing neutrophil infiltration in inflamed muscle.

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