Dataset Information

Investigation of 6-[¹?F]-fluoromaltose as a novel PET tracer for imaging bacterial infection.

ABSTRACT:

Unlabelled

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-[¹?F]-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-[¹?F]-fluoromaltose is taken up by multiple strains of pathogenic bacteria. It is not taken up by mammalian cancer cell lines. 6-[¹?F]-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-[¹?F]-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.

SUBMITTER: Gowrishankar G

PROVIDER: S-EPMC4171493 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gowrishankar Gayatri G Namavari Mohammad M Jouannot Erwan Benjamin EB Hoehne Aileen A Reeves Robert R Hardy Jonathan J Gambhir Sanjiv Sam SS

PloS one 20140922 9

<h4>Unlabelled</h4>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.<h4>Methods</h4>6-[¹⁸F]-fluoromaltose was synthesized. Its behavior in vitro was evaluated in bacterial and mammalian cultures. Detailed pharmacokinetic and biodistributio ...[more]

PMID: 25243851

Similar Datasets

Project description:Microfluidic technologies provide an attractive platform for the synthesis of radiolabeled compounds. Visualization of radioisotopes on chip is critical for synthesis optimization and technological development. With Cerenkov imaging, beta particle emitting isotopes can be localized with a sensitive CCD camera. In order for Cerenkov imaging to also serve as a quantitative tool, it is necessary to understand how material properties relevant to Cerenkov emission, namely, index of refraction and beta particle stopping power, affect Cerenkov light output. In this report, we investigate the fundamental physical characteristics of Cerenkov photon yield at different stages of [(18)F]FDG synthesis on the electrowetting on dielectric (EWOD) microfluidic platform. We also demonstrate how Cerenkov imaging has enabled synthesis optimization. Geant4, a Monte Carlo program applied extensively in high energy physics, is used to simulate Cerenkov photon yield from (18)F beta particles traversing materials of interest during [(18)F]FDG synthesis on chip. Our simulations show that the majority (approximately two-thirds) of the (18)F beta particle energy available to produce Cerenkov photons is deposited on the glass plates of the EWOD chip. This result suggests the possibility of using a single calibration factor to convert Cerenkov signal to radioactivity, independent of droplet composition. We validate our simulations with a controlled measurement examining varying ratios of [(18)O]H2O, dimethyl sulfoxide (DMSO), and acetonitrile (MeCN), and find a consistent calibration independent of solvent composition. However, the calibration factor may underestimate the radioactivity in actual synthesis due to discoloration of the droplet during certain steps of probe synthesis. In addition to the attractive quantitative potential of Cerenkov imaging, this imaging strategy provides indispensable qualitative data to guide synthesis optimization. We are able to use this imaging technique to optimize the mixing protocol as well as identify and correct for loss of radioactivity due to the migration of radioactive vapor outside of the EWOD heater, enabling an overall increase in the crude radiochemical yield from 50 ± 3% (n = 3) to 72 ± 13% (n = 5).

Project description:Overproduction of reactive oxygen species (ROS) is a well-established indicator of ongoing tissue inflammation. However, there is a scarcity of molecular imaging probes capable of providing noninvasive sensitive detection of ROS for allowing longitudinal studies of disease pathology and/or monitoring therapeutic efficacy of ROS scavengers. Herein, we report synthesis and chemical characterization of a novel metalloprobe, Galuminox, a moderately fluorescent agent that detects superoxide and hydrogen peroxide generation. Using live-cell fluorescence imaging analysis, Galuminox demonstrates ability to detect superoxide and monitor effects of ROS-attenuating agents, such as Carvedilol, Dexrazoxane, and mitoTempo in lung epithelial A549 cells. Furthermore, LPS stimulation of A549 cells that either express the mitochondria targeted fluorescent protein Keima or are stained with MitoSOX, a mitochondria-specific superoxide probe, indicates preferential co-localization of Galuminox with mitochondria producing elevated amounts of superoxide. Dynamic PET/CT scans 45 min post tail-vein administration of 68Ga-Galuminox show 4-fold higher uptake and stable retention in lungs of LPS treated mice compared to their saline-only treated counterparts. Post preclinical PET imaging, quantitative biodistribution studies also correlate with 4-fold higher retention of the radiotracer in lungs of LPS treated mice compared with their saline-only treated control counterparts. Consistent with these observations, lung cells isolated from LPS-treated mice demonstrated elevated ROS production deploying CellROX, the ROS probe. Finally, Galuminox uptake correlates with histological and physiological evidence of acute lung injury as evident by polynuclear infiltration, thickening of the alveolar epithelial membranes and increased bronchioalveolar lavage protein content. Taken collectively, these data indicate that 68Ga-Galuminox tracer uptake is a measure of ROS activity in acutely injured lungs and suggests its potential utility in monitoring oxidative stress in other diseases.