Advanced lung imaging using PET and CT scans can reveal whether an experimental anti-TB drug can clear the infection in humans and animals, concludes an international study. The researchers believe their findings should help improve pre-clinical testing of TB drugs to select the ones most likely to be effective in human trials.
The team, led by the University of Pittsburgh School of Medicine, PA, reports the study in the journal Science Translational Medicine.
Tuberculosis (TB) is a global public health problem that is getting worse because the disease is becoming increasingly resistant to available drugs.
JoAnne L. Flynn, professor of microbiology and molecular genetics at Pitt School of Medicine, explains that in 2012, approximately 8.6 million people around the world contracted TB. The challenge in fighting TB is complicated by the fact first-line treatment involves taking four different drugs for up to 8 months to effect a durable cure.
But, as Prof. Flynn explains, around half a million patients a year are not cured – and they can go on to develop multi-drug resistant TB, treatment for which involves taking as many as six drugs for 2 years.
Some of these patients can develop extensively drug-resistant, or XDR-TB, which has a very poor prognosis, she says, adding that:
“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.”
Clinical trials showed that the drug linezolid effectively treated XDR-TB patients – even though mouse studies found it would have no effect.
Using positron emission tomography (PET) and computerized tomography (CT) scans in humans and macaques infected with TB, the team showed that in the majority of cases, “hot spots” in the lungs improved after treatment with linezolid and another drug of the same class.
In humans and macaques, TB infection cause lesions in the lungs that are known as granulomas. These can be seen by PET scans – an imaging approach that injects a tiny amount of radioactive probe that is picked up by the lesion cells – as “hot spots.”
The findings show humans and macaques have similar disease profiles for TB and – in most cases – both show hot spot improvement in PET images following drug treatment.
CT scans – which show anatomical details of the lungs – also showed improvements after treatment with linezolid. There was one case of a patient whose hot spot got worse – but further tests showed the strain of TB he was infected with was resistant to the drug.
The team concludes that:
“PET/CT imaging may be useful as an early quantitative measure of drug efficacy against TB in human patients.”
Prof. Flynn says that by combining a macaque model and PET scanning, trial investigators should be better able to predict which drugs are likely to be effective in human trials and thus speed up getting new treatments into the hands of clinicians.
The scans could also help confirm drug resistance – but they are unlikely to be used routinely – as Prof. Flynn explains:
“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. This might give us a way of tailoring treatment to individuals.”
Funds for the study came from the National Institute of Allergy and Infectious Diseases and the National Cancer Institute, the Ministry of Health and Welfare, the Bill and Melinda Gates Foundation, and the Republic of Korea.
In November 2014, Medical News Today learned how scientists are combining MRI and PET scans to observe Alzheimer’s development. In that study, the researchers believe they laid the groundwork for better diagnostics, for instance to help distinguish Alzheimer’s-related dementia from other diseases.