In This Article
- Pulmonology and imaging innovators at Massachusetts General Hospital have joined forces to study a novel molecular imaging tool in patients with lung fibrosis
- The imaging probe, named 68Ga-CBP8, is injected into the bloodstream and sticks to type I collagen, a key biomarker of fibrosis
- The probe lights up collagen using positron emission tomography. This may allow doctors to track disease activity and response to treatment, better predict prognosis and accelerate the development of new therapies one day
- The tool also may be useful in other types of fibrosis and in other parts of the body
A clinician-researcher team at Massachusetts General Hospital is studying a new molecular imaging tool that recognizes type I collagen. The probe is being used to identify disease activity in pulmonary fibrosis and other conditions, which is critical information for clinicians seeking to establish prognosis and evaluate response to treatment.
"One of the major difficulties in caring for patients with lung fibrosis is that we have no measure for determining how active someone's disease is at any one time," says Sydney Montesi, MD, clinician-researcher in the Division of Pulmonary and Critical Care at Mass General. "Current treatments for idiopathic pulmonary fibrosis may be able to slow down progression, but we have difficulty determining who is actually responding to treatment. There is a need to be able to assess disease activity to improve prognostication and determine treatment response for an individual both in terms of clinical care and clinical trials."
Establishing Effectiveness of the Molecular Imaging Tool
Pulmonary fibrosis is scarring in the lungs caused by drug toxicity, environmental or genetic reasons, radiation, or unknown etiology (e.g., idiopathic pulmonary fibrosis). Overexpression of type I collagen is a hallmark sign.
With funding from the NIH, Dr. Caravan invented a positron emission tomography (PET) probe, called 68Ga-CBP8, that binds to type I collagen. The tool enables collagen to be visualized via PET.
Dr. Caravan published results from mouse models of pulmonary fibrosis in Science Translational Medicine in 2017. That study showed that the probe could detect and quantify the degree of pulmonary fibrosis in mice and measure treatment response.
Then, Dr. Caravan joined with Dr. Montesi to study the probe in humans. Together, they published first-in-human results in the American Journal of Respiratory and Critical Care in 2019. The paper described their successful direct visualization of type I collagen in humans using 68Ga-CBP8 PET.
"Our research suggests that this method is more sensitive to detecting early regions of fibrosis than current radiological techniques," Dr. Caravan says. "We're seeing things that you can't see via traditional measures."
Measuring Treatment Response
The Mass General team is now designing a clinical study funded by the American Thoracic Society examining whether 68Ga-CBP8 PET can measure the response to treatment for lung fibrosis. The clinical trial, to be performed at the Athinoula A. Martinos Center for Biomedical Imaging, involves administering the probe intravenously before a PET scan. Areas of collagen that take up the probe appear as bright areas on the scan. After a course of treatment, the researchers will repeat 68Ga-CBP8 PET and compare findings to determine whether the treatment has lessened fibrosis.
The probe has been safe and well tolerated in 19 individuals so far. "We're injecting such a small amount—less than a hundred micrograms, less than a grain of salt," says Dr. Caravan.
Clinical Need and Developing New Drugs
The team is excited about the probe's ability to fill a gap in the management of lung fibrosis.
"This tool has wonderful features that meet a clinical need. Current treatments for idiopathic pulmonary fibrosis are shown to work on the population level, but we don't know on an individual level how well a patient is responding to treatment," Dr. Montesi says. "What's unique about this probe is that we think it's more sensitive to finding freshly synthesized collagen as opposed to established collagen. We can use it not so much to stage disease—because we can do that by current techniques—but really to get a sense of disease activity."
Dr. Caravan says the technology will also accelerate the clinical development of new drugs.
"There's a lot of pharmaceutical activity in idiopathic pulmonary fibrosis, but historically it's been a very difficult area," Dr. Montesi says. "We would really like to be able to stratify patients based on disease activity, as well as tell in a short amount of time whether or not a drug is working."
Dr. Montesi recently competed in the American Thoracic Society's BEAR Cage (Building Education to Advance Research) Competition, which is an opportunity for early career researchers to share their research and innovation with members of academia, industry and government who engage in translational science. She was awarded this year's BEAR Cage Innovation Award.
Applying to Other Diseases
"The overarching goal of our work is to bring this technology to other diseases as well," Dr. Caravan says. "It can be used in any condition with increased collagen. We can use the same probe and just point the camera at a different part of the body."
Examples of such conditions include:
- Crohn's disease
- Desmoplastic response in pancreatic cancer
- Interstitial lung disease
- Radiation-induced lung injury in patients with cancer
- Systemic sclerosis
Furthermore, Dr. Montesi says, "Different conditions might have different needs. For pulmonary fibrosis, we need a disease activity measure. But for cirrhosis, we might need a staging measure. In different conditions, you can use the same tool in a different study design or at a different time in the course of a disease to get different information." Dr. Caravan is also developing other probes for different targets, such as fibrin in blood clots.
"Mass General is just an incredibly collaborative environment," Dr. Caravan says. "The physicians constantly innovate and are on the lookout for new technologies that could benefit their patients."
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