Utilizing 18F-fluoroglutamine PET Imaging in Patients With Pulmonary Arterial Hypertension
Stephen Y. Chan
Summary
Pulmonary arterial hypertension (PAH) is mortal disease affecting the blood vessels of the lung. Despite its morbid prognosis, PAH is often misdiagnosed or ignored, with an average time of 44 months between onset of symptoms to diagnosis and substantial progression of disease severity. Therefore, a pressing need exists to develop non-invasive diagnostic imaging tools, particularly that can detect early disease stages. Efforts have been made to develop such imaging capabilities through platform development of echocardiography, cardiac MRI, chest computed tomography (CT), and positron emission tomography (PET), among others. While some have demonstrated promise, few have shown a precise ability to offer disease quantifications of the diseased lung and vasculature itself, to detect early stages of disease, and to reflect alterations of the lung, vasculature, and right ventricle that reflect the molecular origins of this disease. \[F-18\]FGln has been previously utilized in oncology studies as a non-invasive in vivo imaging biomarker of tumor glutamine flux and metabolism. Our preliminary in vivo pre-clinical rodent studies demonstrated that \[F-18\]FGln demonstrated increased uptake in diseased pulmonary vessels and the right ventricle in a rodent model of PAH. The proposed research study will provide preliminary evidence of the potential to utilize \[F-18\]FGln as a non-invasive imaging biomarker of glutamine flux and metabolism across a range of PAH subjects.
Description
Objective: Investigators will conduct in-human PET imaging of 18F-fluoroglutamine (18F-FGln) in patients with PAH to compare glutamine uptake to that of controls. Specific Aim: Utilizing18F-FGln PET imaging to measure pathogenic glutamine uptake in patients with PAH or eiPAH and controls. Significance: Investigator multi-disciplinary team, comprised of Drs. Chan, Tavakoli, and Mason are already actively collaborating together, and are uniquely positioned to image and quantify glutamine uptake in this special patient population. In doing so, investigators will determine the potential of this…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: Cases: 1. Age between 18-75 years old 2. Confirmed diagnosis of SSc-PAH / SSc-eiPAH/IPAH/ by right heart catheterization. And Scleroderma with no PAH confirmand by echo. Controls: 1. Age between 18-75 years old 2. Individuals who are at low risk for current or future cardiovascular or pulmonary symptoms or diseases Exclusion Criteria: Cases: 1. Smoking 2. Pregnant/ breast feeding women 3. Children under 18 4. Inability to read and understand the informed consent 5. History of CT contrast allergy 6. Inability to lie down for long period of time 7. Having claustrophobi…
Interventions
- Diagnostic Test18F-FGLN PET Imaging
PET/CT Imaging: The study visit will take around 3-4 hours, the duration of PET will be around 90 minutes. Women should have negative pregnancy test prior to the study. An intravenous catheter will be placed in the subject's opposite arm, which will be used for radiotracer administration. A low-dose helical CT scan will be performed during a \~15 sec inspiratory breath hold and used for CT-based attenuation correction of PET emission data and as an anatomical reference for image analyses. Participants will be retained in the PET facility following the PET scan to promote urination to increase elimination of the radiotracer.
- Drug(18F)FPGLU
\[F-18\]FGln is a natural glutamine derivative was synthesized to explore its potential application of imaging glutamine uptake for cancer diagnosis. The proposed research study will provide preliminary evidence of the potential to utilize \[F-18\]FGln as a non-invasive imaging biomarker of glutamine flux and metabolism across a range of PAH subjects.
Location
- Montefiore Hospital Clinical and Translational Research CenterPittsburgh, Pennsylvania