PLoS ONE (Jan 2017)

The biodistribution of 5-[18F]fluoropyrazinamide in Mycobacterium tuberculosis-infected mice determined by positron emission tomography.

  • Zhuo Zhang,
  • Alvaro A Ordonez,
  • Peter Smith-Jones,
  • Hui Wang,
  • Kayla R Gogarty,
  • Fereidoon Daryaee,
  • Lauren E Bambarger,
  • Yong S Chang,
  • Sanjay K Jain,
  • Peter J Tonge

DOI
https://doi.org/10.1371/journal.pone.0170871
Journal volume & issue
Vol. 12, no. 2
p. e0170871

Abstract

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5-[18F]F-pyrazinamide (5-[18F]F-PZA), a radiotracer analog of the first-line tuberculosis drug pyrazinamide (PZA), was employed to determine the biodistribution of PZA using PET imaging and ex vivo analysis. 5-[18F]F-PZA was synthesized in 60 min using a halide exchange reaction. The overall decay-corrected yield of the reaction was 25% and average specific activity was 2.6 × 106 kBq (70 mCi)/μmol. The biodistribution of 5-[18F]F-PZA was examined in a pulmonary Mycobacterium tuberculosis mouse model, where rapid distribution of the tracer to the lung, heart, liver, kidney, muscle, and brain was observed. The concentration of 5-[18F]F-PZA was not significantly different between infected and uninfected lung tissue. Biochemical and microbiological studies revealed substantial differences between 5-F-PZA and PZA. 5-F-PZA was not a substrate for pyrazinamidase, the bacterial enzyme that activates PZA, and the minimum inhibitory concentration for 5-F-PZA against M. tuberculosis was more than 100-fold higher than that for PZA.