PET or positron emission tomography is used to create an image of activity in internal organs and tissues, to help determine how well they are working. It is also known as nuclear medicine.

PET may be used in clinical trials to help determine an investigative compound’s effectiveness in treating a given disease, including pulmonary hypertension. In the case of pulmonary hypertension, in fact, PET is also being explored in clinical studies as a way to help diagnose the disease and track its progression.

How PET works

PET requires the use of a radiopharmaceutical, which is injected, swallowed or inhaled, to examine a particular organ or tissue. A radiopharmaceutical is generally a radioactive “tracer” combined with a substance or medication that targetd a specific tissue or chemical reaction (high levels of chemical activity are often found in areas with disease).

The pharmaceutical agent ensures that the tracer will build up in select tissue, and the attached radioactive component releases energy that can be picked up by the PET scanner — the areas show as bright spots.

These scans can reveal information about the chemical activity of the organs being studied, and can be used to assess how well it is functioning at a metabolic level.

Examples of common radiopharmaceuticals include [11C]-Acetate and [18F]-Flurodeoxyglucose (FDG). Both are used to track glucose metabolism in the heart, lungs, and brain, as they can measure glucose uptake in these tissues. Glucose is essential in producing energy in tissues, and tracking this can provide information on the health of the heart and lungs, which could be used to assess the progression of pulmonary hypertension and estimate clinical outcomes.

An example of a pre-clinical study of PET, using two rat models of pulmonary arterial hypertension (PAH), was published in the American Journal of Respiratory and Critical Care Medicine. This study demonstrated that [18F]-FDG=based PET could be used to detect even mild cases of PAH and could show disease regression in response to PAH therapies.

Examples of PET in clinical trials

PET scans have been used in multiple clinical trials for pulmonary hypertension, both to test potential therapies and as a potential diagnostic tool.

For example, an ongoing Phase 2 trial (NCT01917136) is using a combination of [11C]-Acetate and [18F]-FDG PET scans with cardiac magnetic resonance imaging (MRI), another type of imaging test, to assess metabolic and structural changes in the hearts of pulmonary hypertension patients. These people are also enrolled in another trial (NCT01839110) that is assessing the effect of ranolazine, a treatment for chronic angina, compared to a placebo in treating pulmonary hypertension with right ventricular dysfunction. The trial, sponsered by the University of Pennsylvania, is fully enrolled and is expected to be completed in December 2018, as does the PET scan study.

A pilot study (NCT02237378), sponsored by the Ottawa Heart Institute Research Corporation, is currently recruiting participants with PAH to use FDG-based PET scanning to assess the mechanisms that could contribute to heart failure, one of the leading causes of death in PAH. The trial aims to enroll 10 patients in Ontario, and is expected to finish in May 2019.

A Phase 1/2 clinical trial (NCT03166306), sponsored by the Brigham and Women’s Hospital in Boston, aims to test the sensitivity of PET scans using the radiopharmaceutical [89Zr]-bevacizumab in improving rates of early PAH diagnosis and in a non-invasive manner. Bevacizumab is an cancer therapy (brand name, Avastin), but here it being used here for its ability to target the protein vascular endothelial growth factor (VEGF), a marker of pulmonary blood vessel remodeling.

The researchers theorize that PAH patients may have an increase in changes in the blood vessels in the lungs, signaled by VEGF, compared to healthy participants, and that examining such changes using PET scans could result in an earlier diagnosis — one prior to the onset of more severe symptoms. The trial aims to recruit 30 people: 10 healthy volunteers, 10 patients with severe PAH, and 10 patients with very early stage PAH. The trial has not yet started recruiting.

Other information

Radiopharmaceuticals are generally used in very low doses, and as a result, the patient’s exposure to radiation is minimal and targeted to a localized area. The risk of the procedure is considered to be low.

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