Braams, L.M. (2017) Nuclear Imaging of Infection : Developemnt of a 2-[18F] fluorodeoxysorbitol tracer for the detection of bacterial infection using positron emission tomography. thesis, Medicine.
Full text available on request.Abstract
Introduction Bacterial infections are a major clinical challenge in almost all medical fields, especially because the diagnosis and treatment are complex. There is a global threat of antibiotic resistance development and a lack of fast and accurate diagnostic tools. Currently, the golden standard in diagnostics is microbial culturing and molecular analysis. This usually requires sampling at the site of infection, which can be very difficult and invasive in deeply- seated infections. Furthermore, it can take several days before the causative agent is identified, while in the meantime a blind treatment of broad-spectrum antibiotics is initiated. This blind treatment approach causes over- and undertreatment of the patient, with induction of antibiotic resistance, morbidity, side-effects and mortality as a result. Imaging of inflammation and infection is a faster method, however, current anatomical and functional modalities cannot differentiate between (sterile) inflammation and bacterial infection. A solution can be found in the new field of bacterial targeted imaging, which uses tracers that target bacteria specifically. In the last few years, different bacterial targeted tracers have been developed for nuclear imaging (Positron Emission Tomography, PET) or optical imaging. In this study, the PET-tracer 2-[18F]-fluorodeoxysorbitol (18F-FDS) will be assessed in vitro. Sorbitol is a sugar that is selectively metabolized by bacteria of the Enterobacteriaceae family. Among other things, this makes 18F-FDS a very promising PET- tracer to targeted these bacteria. Material and Methods 18F-FDS is synthesized (using good manufacturing practise) by reducing in-house produced 18F-FDG at the department of Nuclear Medicine and Molecular Imaging at the University Medical Centre Groningen (UMCG). Purity assessment of the tracer has been done by thin liquid chromatography. Different clinical isolates and (infected) patient materials (blood and ascites fluid) were collected from the department of Medical Microbiology at the UMCG, which made up a broad assay of clinically relevant strains. Fresh cultures were made of the clinical isolates, which were grown to an optical density (OD) of ~1-2 McFarland and subsequently incubated with 3- 15 MBq 18F-FDS for 60 minutes. The bacterial pellets were washed twice with phosphate buffered saline (PBS), and analysed with a gamma-counter ((Wizard2, Perkin Elmer, USA) for radioactivity. Thereafter, the bacteria were diluted and plated onto blood agar plates, for colony forming units (CFU) counting. The outcome measure is the absorbed activity correlated to the amount of CFU (Bq/CFU). Controls consisted of heatkilled cultures, non- infected patient materials and non-incubated samples. Results As expected, clinical isolates from the family Enterobacteriaceae accumulated 18F- FDS very well. Also, Pseudomonas aeruginosa and Corynebacterium. jeikeium showed uptake of the tracer. 18F-FDS was successful in detecting infected patient materials. Conclusie Based on the results presented in this study, it can be concluded that 18F-FDS is a promising bacterial-targeted radionuclear tracer for clinical translation.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Dijl, Prof dr. J.M. and Oosten, Dr. M. van and Department of Medical Microbiology and UMCG |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:41 |
| Last Modified: | 25 Jun 2020 10:41 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/314 |
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