The use of 14C-FIAU to predict bacterial thymidine kinase presence

Implications for radiolabeled FIAU bacterial imaging

Kristin L. Peterson, William C. Reid, Alexandra F. Freeman, Steven M. Holland, Roderic I. Pettigrew, Ahmed M. Gharib, Dima A. Hammoud

Research output: Contribution to journalArticle

Abstract

Currently available infectious disease imaging techniques cannot differentiate between infection and sterile inflammation or between different types of infections. Recently, radiolabeled FIAU was found to be a substrate for the thymidine kinase (TK) enzyme of multiple pathogenic bacteria, leading to its translational use in the imaging of bacterial infections. Patients with immunodeficiencies, however, are susceptible to a different group of pathogenic bacteria when compared to immunocompetent subjects. In this study, we wanted to predict the usefulness of radiolabeled FIAU in the detection of bacterial infections commonly occurring in patients with immunodeficiencies, in vitro, prior to attempting in vivo imaging with 124I-FIAU-PET. Methods: We obtained representative strains of bacterial pathogens isolated from actual patients with genetic immunodeficiencies. We evaluated the bacterial susceptibility of different strains to the effect of incubation with FIAU, which would implicate the presence of the thymidine kinase (TK) enzyme. We also incubated the bacteria with 14C-FIAU and consequently measured its rate of incorporation in the bacterial DNA using a liquid scintillation counter. Results: Unlike the other bacterial strains, the growth of Pseudomonas aeruginosa was not halted by FIAU at any concentration. All the tested clinical isolates demonstrated different levels of 14C-FIAU uptake, except for P. aeruginosa. Conclusion: Radiolabeled FIAU has been successful in delineating bacterial infections, both in preclinical and pilot translational studies. In patients with immunodeficiencies, Pseudomonas infections are commonly encountered and are usually difficult to differentiate from fungal infections. The use of radiolabeled FIAU for in vivo imaging of those patients, however, would not be useful, considering the apparent lack of TK enzyme in Pseudomonas. One has to keep in mind that not all pathogenic bacteria possess the TK enzyme and as such will not all retain FIAU. Our technique is simple, and can be easily used to assess whether a certain bacterial strain of interest can or cannot be visualized using radiolabeled FIAU.

Original languageEnglish (US)
Pages (from-to)638-642
Number of pages5
JournalNuclear Medicine and Biology
Volume40
Issue number5
DOIs
StatePublished - Jul 2013
Externally publishedYes

Fingerprint

Thymidine Kinase
Bacterial Infections
Bacteria
Enzymes
Pseudomonas aeruginosa
fialuridine
Pseudomonas Infections
Scintillation Counting
Bacterial DNA
Mycoses
Pseudomonas
Infection
Communicable Diseases
Inflammation

Keywords

  • Bacterial imaging
  • FIAU
  • PET
  • Thymidine kinase

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

Peterson, K. L., Reid, W. C., Freeman, A. F., Holland, S. M., Pettigrew, R. I., Gharib, A. M., & Hammoud, D. A. (2013). The use of 14C-FIAU to predict bacterial thymidine kinase presence: Implications for radiolabeled FIAU bacterial imaging. Nuclear Medicine and Biology, 40(5), 638-642. https://doi.org/10.1016/j.nucmedbio.2013.01.005

The use of 14C-FIAU to predict bacterial thymidine kinase presence : Implications for radiolabeled FIAU bacterial imaging. / Peterson, Kristin L.; Reid, William C.; Freeman, Alexandra F.; Holland, Steven M.; Pettigrew, Roderic I.; Gharib, Ahmed M.; Hammoud, Dima A.

In: Nuclear Medicine and Biology, Vol. 40, No. 5, 07.2013, p. 638-642.

Research output: Contribution to journalArticle

Peterson, KL, Reid, WC, Freeman, AF, Holland, SM, Pettigrew, RI, Gharib, AM & Hammoud, DA 2013, 'The use of 14C-FIAU to predict bacterial thymidine kinase presence: Implications for radiolabeled FIAU bacterial imaging', Nuclear Medicine and Biology, vol. 40, no. 5, pp. 638-642. https://doi.org/10.1016/j.nucmedbio.2013.01.005
Peterson, Kristin L. ; Reid, William C. ; Freeman, Alexandra F. ; Holland, Steven M. ; Pettigrew, Roderic I. ; Gharib, Ahmed M. ; Hammoud, Dima A. / The use of 14C-FIAU to predict bacterial thymidine kinase presence : Implications for radiolabeled FIAU bacterial imaging. In: Nuclear Medicine and Biology. 2013 ; Vol. 40, No. 5. pp. 638-642.
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abstract = "Currently available infectious disease imaging techniques cannot differentiate between infection and sterile inflammation or between different types of infections. Recently, radiolabeled FIAU was found to be a substrate for the thymidine kinase (TK) enzyme of multiple pathogenic bacteria, leading to its translational use in the imaging of bacterial infections. Patients with immunodeficiencies, however, are susceptible to a different group of pathogenic bacteria when compared to immunocompetent subjects. In this study, we wanted to predict the usefulness of radiolabeled FIAU in the detection of bacterial infections commonly occurring in patients with immunodeficiencies, in vitro, prior to attempting in vivo imaging with 124I-FIAU-PET. Methods: We obtained representative strains of bacterial pathogens isolated from actual patients with genetic immunodeficiencies. We evaluated the bacterial susceptibility of different strains to the effect of incubation with FIAU, which would implicate the presence of the thymidine kinase (TK) enzyme. We also incubated the bacteria with 14C-FIAU and consequently measured its rate of incorporation in the bacterial DNA using a liquid scintillation counter. Results: Unlike the other bacterial strains, the growth of Pseudomonas aeruginosa was not halted by FIAU at any concentration. All the tested clinical isolates demonstrated different levels of 14C-FIAU uptake, except for P. aeruginosa. Conclusion: Radiolabeled FIAU has been successful in delineating bacterial infections, both in preclinical and pilot translational studies. In patients with immunodeficiencies, Pseudomonas infections are commonly encountered and are usually difficult to differentiate from fungal infections. The use of radiolabeled FIAU for in vivo imaging of those patients, however, would not be useful, considering the apparent lack of TK enzyme in Pseudomonas. One has to keep in mind that not all pathogenic bacteria possess the TK enzyme and as such will not all retain FIAU. Our technique is simple, and can be easily used to assess whether a certain bacterial strain of interest can or cannot be visualized using radiolabeled FIAU.",
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