New Probe Specifically Targeting Collagen in Lungs Promises to Improve PF Diagnosis, Treatment

A new imaging strategy shows promising results in improving the diagnosis and treatment of people with pulmonary fibrosis (PF). The study, “Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models,” appeared in the journal Science Translational Medicine.

Scientists at Massachusetts General Hospital (MGH) have developed a probe that specifically targets collagen, which is produced in excess in fibrotic tissue. The collagen-targeting probe, called 68Ga-CBP8, is to be used in peptide-based positron emission tomography (PET).

Researchers showed that the probe bound to scar tissue in the lungs of two animal models of PF, including the well-established bleomycin-induced mouse model.

The amount of probe binding in the animals’ lungs correlated with the amount of collagen present. Scientists also showed that the 68Ga-CBP8 probe not only determines the extent of fibrosis, but also reduces it in mice treated with an anti-fibrotic drug. Therefore, it can also be used to monitor response to treatment.

Researchers corroborated their findings in human lung samples, demonstrating that the newly developed probe was also capable of differentiating between stable disease and progressive fibrosis — which is important when considering what type of treatment to use.

“Increased collagen production is a hallmark of fibrosis in the lungs and in other organs,” Peter Caravan, PhD, said in a press release. Caravan is the study’s co-corresponding author at the Athinoula A. Martinos Center for Biomedical Imaging and co-director of MGH’s Institute for Innovation in Imaging.

“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,” Caravan added. “Non-invasive PET imaging with 68Ga-CBP8 provides information on the entire lung without a biopsy, which would only reflect a small portion of the lung.”

PET technology is much better at diagnosing PF than conventional CT scanning, because PET can detect and quantify collagen molecules, while CT scanning just measures structural abnormalities, which may be caused by conditions other than PF. In addition, the team’s findings showed that 68Ga-CBP8 only bounded to collagen in a mouse model of PF, while no signal was detected in the lungs of healthy animals.

“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, of the MGH Division of Thoracic Surgery. “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. 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.”

Now, scientists are drafting the required documentation to test 68Ga-CBP8 in patients. That trial will likely begin later this year, with funding from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health.