PET solves the riddle of drug resistance in tuberculosis research

Dual human and preclinical PET scans shine a light on treatments for tuberculosis (TB) and aid in drug discovery and selection, according to researchers at the University of Pittsburgh School of Medicine. University officials announced on Dec. 3 the results of a pivotal study noting that quantitative PET was earmarked for future clinical trials.

Approximately 8.6 million people contracted TB across the globe in 2012, according to the report featuring study co-author JoAnne L. Flynn, PhD, a professor of microbiology and molecular genetics at the University of Pittsburgh School of Medicine. Those who develop the disease must take a cocktail of drugs to combat it. Flynn estimated that about 500,000 of these patients go on to develop multi-drug resistant TB. Some patients are administered up to six drugs for two years to fight the infection.

“Some of those people don’t get cured, either, and develop what we call extensively drug-resistant, or XDR, TB, which has a very poor prognosis,” said Flynn in the press release. “Our challenge is to find more effective treatments that work in a shorter time period, but the standard preclinical models for testing new drugs have occasionally led to contradictory results when they are evaluated in human trials.”

For this study, researchers evaluated oxazolidinone antibiotic monotherapy of either linezolid or AZD5847 in animal models of XDR TB using FDG PET and CT as well as simultaneous PET/CT scanning in humans taking linezolid. The research findings showed how these drugs pushed bacterial loads back down via reduced hot spots in the lungs and fewer signs of pathology on CT scans. This technique could one day be used in phase III human trials for new new TB treatments.

“We plan to use this PET scanning strategy to determine why some lesions don’t respond to certain drugs, and to test candidate anti-TB agents,” added Flynn. “This might give us a way of tailoring treatment to individuals.”