Potential PET tracer could help to identify PF at early stages

Imaging agent likely specific to disease, more efficient at monitoring patients

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A new, potentially disease-specific imaging agent may one day allow doctors to identify pulmonary fibrosis (PF) in earlier stages, when the start of treatment can be more effective, according to a study in a mouse model of the disease.

Called 64Cu-GPVI-Fc, the agent — coupled with positron emission tomography (PET), used to capture the tracer in the body — could minimize the need for a biopsy to examine changes in lung tissue, and aid in monitoring disease progression and treatment response.

“Molecular imaging of the biomarkers of pulmonary fibrosis could lead to earlier detection and better monitoring, as well as provide a novel way to assess treatment efficacy,” Nicolas Bézière, PhD, who led the study, said in a press release. Bézière is head of imaging of infection and inflammation at the Werner Siemens Imaging Center, part of Eberhard Karls University of Tübingen in Germany.

The study, “Radiolabeled GPVI-Fc for PET Imaging of Multiple Extracellular Matrix Fibers: A New Look into Pulmonary Fibrosis Progression,” was published in The Journal of Nuclear Medicine.

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Current tests to diagnose PF cannot catch disease in its earlier stages

PF is marked by the excessive buildup of scar tissue in the lungs. The extracellular matrix, a mesh-like network of molecules that surrounds and supports cells within tissues, is thought to play a key role in scar tissue formation.

Doctors usually diagnose PF based on lung function tests and CT, or CAT scan, images of the lungs. But such imaging isn’t always enough to detect the disease in its earlier stages.

“Currently, routine clinical diagnosis of pulmonary fibrosis relies on breathing tests and visualizing the changes in lung structure with CT, but this anatomical information is often not sufficient to identify early signs of the disease,” Bézière said.

PET is usually used to track 18F-FDG, a tracer that contains radioactive glucose (sugar). A small amount of the tracer is injected into a patient’s bloodstream, and a scanner takes a picture showing where the glucose is taken up in the body.

Cells in inflamed, fast-growing tissues often take up more glucose than cells in healthy tissues, showing up brighter on the picture. However, 18F-FDG’s use in PF is limited because it’s not specific to this disease.

New tracer showed ‘significant uptake’ by cells in fibrotic lung tissue

Bézière’s team developed 64Cu-GPVI-Fc, a tracer that contains a radioactive platelet glycoprotein VI fusion protein. Glycoprotein VI is only present in platelets, tiny cell fragments that help wounds heal, where it acts as a receptor that binds collagen — a key component of the extracellular matrix.

To test whether 64Cu-GPVI-Fc might be specific to PF, the team turned to mice in which the disease was triggered by exposing the animals to the chemical bleomycin.

Bleomycin soon begins to cause inflammation in the lungs, which then progresses to fibrosis about one week later, with excessive production of collagen and the buildup of fibrous tissue. This phase is followed by the remodeling of lung tissue.

64Cu-GPVI-Fc was taken up by fibrous tissue in the lungs, matching what researchers saw when they looked at that tissue under a microscope. But unlike 18F-FDG, which was evident in about the same amount during each of the above phases, 64Cu-GPVI-Fc was taken up mainly during the active fibrosis stage.

The investigative agent “showed significant uptake in fibrotic lungs,” the researchers wrote. Contrary to 18F-FDG measures on PET scans, 64Cu-GPVI-Fc uptake “was linked entirely to the fibrotic activity of tissue and not was susceptible to inflammation.”

“It is critical that proper diagnosis and treatment follow-up methods are specific and sensitive enough that optimal medical care can be given,” Bézière said. “We believe 64Cu-GPVI-Fc takes us one step closer to personalized medicine for pulmonary fibrosis.”

Findings suggest that 64Cu-GPVI-Fc may be specific to changes in the extracellular matrix occurring early in PF’s development, meaning it might be able to help doctors in clinical practice diagnose and treat the disease more effectively.

“We hope that this approach based on a tracer targeting a range of extracellular matrix fibers will provide a new way to view the ‘complete picture’ of pulmonary fibrosis progression,” Bézière said.

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