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

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0170871
JournalPLoS One
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2017

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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