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

<p>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 <i>E.coli</i> in the infected muscle section. D) Representative H&E stained muscle sections showing neutrophil infiltration in inflamed muscle.</p

Investigation of 6-[¹⁸F]-Fluoromaltose as a Novel PET Tracer for Imaging Bacterial Infection

<div><p></p><p>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.</p><p>Methods</p><p>6-[¹⁸F]-fluoromaltose was synthesized. Its behavior <i>in vitro</i> was evaluated in bacterial and mammalian cultures. Detailed pharmacokinetic and biodistribution profiles for the tracer were obtained from a murine model.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>We have shown that 6-[¹⁸F]-fluoromaltose can be used to image bacterial infection <i>in vivo</i> with high specificity. We believe that this class of agents will have a significant impact on the clinical management of patients.</p></div

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

<p>A) A coronal slice from a PET/CT image of a mouse bearing 10⁸ CFU of viable bioluminescent <i>E.coli</i> on the right thigh (red arrow) and 10⁸ CFU of heat-inactivated <i>E.coli</i> 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.</p

<i>In vivo</i> characterization of 6-[¹⁸F]-fluoromaltose.

<p>A) 3D color map from a PET/CT scan of a mouse bearing <i>E.coli</i> 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).</p

<i>In vitro</i> characterization of 6-[¹⁸F]-fluoromaltose.

<p>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 <i>E.coli</i> in the presence of 1 mM maltose. C) Bioluminescence imaging of a macrophage cell line J774 infected with a bioluminescent strain of <i>Listeria monocytogenes.</i> D) 1 hour uptake of 6-[¹⁸F]-fluoromaltose in the bioluminescent strain of <i>Listeria monocytogenes</i> and in macrophage cell line J774 with and without intracellular <i>Listeria</i> infections.</p