The biodistribution of 5-[18F]fluoropyrazinamide in Mycobacterium tuberculosis-infected mice determined by positron emission tomography.
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.
Institute for Chemical Biology & Drug Discovery, Department of Chemistry and Department of Radiology, Stony Brook University, Stony Brook, New York, United States of America.
Zhuo
http://orcid.org/0000-0003-3686-409X
Z
Zhang
Center for Infection and Inflammation Imaging Research, Center for Tuberculosis Research and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Alvaro A
AA
Ordonez
The Facility for Experimental Radiopharmaceutical Manufacturing, Department of Psychiatry, Stony Brook University, Stony Brook, New York, United States of America.
Peter
P
Smith-Jones
Institute for Chemical Biology & Drug Discovery, Department of Chemistry and Department of Radiology, Stony Brook University, Stony Brook, New York, United States of America.
Hui
H
Wang
Institute for Chemical Biology & Drug Discovery, Department of Chemistry and Department of Radiology, Stony Brook University, Stony Brook, New York, United States of America.
Kayla R
KR
Gogarty
Institute for Chemical Biology & Drug Discovery, Department of Chemistry and Department of Radiology, Stony Brook University, Stony Brook, New York, United States of America.
Fereidoon
F
Daryaee
Center for Infection and Inflammation Imaging Research, Center for Tuberculosis Research and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Lauren E
LE
Bambarger
Center for Infection and Inflammation Imaging Research, Center for Tuberculosis Research and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Yong S
YS
Chang
Center for Infection and Inflammation Imaging Research, Center for Tuberculosis Research and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Sanjay K
SK
Jain
Institute for Chemical Biology & Drug Discovery, Department of Chemistry and Department of Radiology, Stony Brook University, Stony Brook, New York, United States of America.
Peter J
PJ
Tonge
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D000995:Antitubercular Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008809:Mice, Inbred C3H; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D000072078:Positron Emission Tomography Computed Tomography; D011718:Pyrazinamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013379:Substrate Specificity; D014018:Tissue Distribution; D014397:Tuberculosis, Pulmonary / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000382:microbiology
D000995:Antitubercular Agents; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D011718:Pyrazinamide; D000581:Amidohydrolases; C022490:pyrazinamide deamidase