Researchers developed a new probe to use in positron emission tomography (PET) imaging that may help diagnose and monitor pulmonary fibrosis, according to a study. The probe, called 68Ga-CBP8, binds to fibrotic lung tissue and allows doctors to follow the lungs’ response to treatment.
Results of this work were published in the journal Science Translational Medicine, titled “Type I Collagen–Targeted PET Probe For Pulmonary Fibrosis Detection And Staging In Preclinical Models.”
Tissue fibrosis is difficult to visualize and diagnose using noninvasive methods, which led Peter Caravan, PhD, and his research team to develop an imaging probe for PET scans that detects type 1 collagen, a protein that accumulates in fibrotic tissues.
PET scans can detect and quantify collagen molecules, which provide much more detailed information than CT scans, which only reveal structural anomalies in the lungs.
The team used mice with induced pulmonary fibrosis to validate the sensitivity of the probe. They observed that the 68Ga-CBP8 probe was able to detect fibrotic lung tissue. Importantly, it also detected fibrosis in lung samples obtained from patients with idiopathic pulmonary fibrosis (IPF).
The overall uptake of the probe was as high as the level of fibrosis in the tissue — that is, the more affected the lungs, the more the probe signaled for fibrosis during the scans.
“Increased collagen production is a hallmark of fibrosis in the lungs and in other organs,” Caravan said in a news release.
“High-resolution CT scanning can precisely diagnose only 50 percent of patients and often cannot predict prognosis or show response to therapies, making invasive biopsy – which can be hazardous to these patients – the only definitive diagnostic method,” he added. “Noninvasive PET imaging with 68Ga-CBP8 provides information on the entire lung without a biopsy, which would only reflect a small portion of the lung.”
Additional experiments showed that disease progression is accompanied by increased uptake of 68Ga-CBP8, suggesting the probe can serve as a fibrosis biomarker to monitor over time. In addition, reductions in fibrosis caused by an experimental antibody-based drug were also successfully followed with the new probe.
“The ability of molecular PET imaging with this probe to detect early-stage fibrosis would allow us to begin treatment when it would be most effective,” said Michael Lanuti, MD, the other senior author of the study.
“This probe may also be able to distinguish new, active fibrosis from stable disease, which would allow clinicians to better tailor therapy to individual patients,” he said. “And since response to therapy is difficult to ascertain with high-resolution CT scanning, PET molecular imaging may be a more sensitive way to detect changes in active fibrosis.”
Based on these results, the team is planning a request for a clinical trial testing the use of 68Ga-CBP8 in patients. The team has already been granted financial support for the trial by the National Heart, Lung and Blood Institute (NHLBI).
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