in the Center, developing neural network-based image reconstruction techniques.
Currently, biopsy is the gold standard in detecting and staging fibrosis. But this solution is in many ways limited. It suffers sampling error, since it only measures 1 / 50,000th of the entire liver, which is not necessarily representative of the rest of the organ. And because it is an invasive procedure there is always a risk of complications. Indeed, as many as five percent of biopsy cases result in hospitalization. For these reasons, noninvasive methods that can image the entire liver, repeatedly with little or no chance of complications, would be of tremendous value in the clinic.
Zhu and colleagues looked at two such methods. First was magnetic resonance elastography( MRE). Over the past decade researchers have focused increasing attention on this technique because of its ability to assess liver fibrosis by imaging the stiffness of the tissue. MRE can reliably stage advanced fibrosis as this is when the tissue stiffens the most. But it is less effective at detection and staging of early fibrosis when interventions could still stem or even reverse the progression of fibrosis.
This is where the second approach comes in. In more recent years, Peter Caravan’ s group in the Center has developed a gadolinium-based MR contrast agent, EP-3533, that
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New PET Probe Images Fibrosis of the Lungs
In a different study, the Martinos Center’ s Pauline Désogère and colleagues have described a new positron emission tomography( PET) probe that can help to advance noninvasive diagnosis of pulmonary fibrosis. Reported in a Science Translational Medicine paper published online in April, the probe enables detection and staging of the disease by imaging Type I collagen, a major component of fibrosis.
In current practice, high-resolution computed tomography is commonly used for diagnosis of the disease, but the technique often cannot distinguish between fibrosis and other pathological processes in the lung. It can precisely diagnose only 50 percent of patients, and in many cases is not able to predict prognosis or show response to therapies. This leaves surgical biopsy as the only available method for definitive diagnosis, and biopsy can be particularly hazardous to the patients in question.
Désogère sought to change this.
An instructor in the Center working in the laboratory of Peter Caravan, Désogère developed the new probe by modifying a collagen-specific peptide to bind with the radioisotope Gallium-68, commonly written as 68Ga. Interest in 68Ga probes has increased dramatically over the past year and a half, especially as the short half-life of the radioisotope allows relatively easy production and leads to low radiation exposure in subjects. With an eye toward clinical translation with PET, Désogère, Caravan and colleagues tested the collagen-targeted probe— 68Ga-CBP8— in a mouse model of pulmonary fibrosis and found high specificity for the disease. In another model, they showed that the probe could also be used to monitor response to treatment. Finally, experiments using ex vivo samples of fibrotic human lung tissue suggested that the probe could differentiate between stable disease and progressive fibrosis— information that can be important to treatment planning.
The introduction of the probe is timely. The US Food and Drug Administration recently approved two drugs that slow the progression of idiopathic pulmonary fibrosis— a form of the disease that affects mostly older adults— and of associated loss of function in the lungs. Investigators are also exploring the potential of the drugs for other forms of the disease. With these new possibilities for treatment, early detection of the disease, accurate prognosis and the ability to monitor treatment response become ever more important. The 68Ga-CBP8 probe could enable these, reliably and noninvasively, and thus could benefit a wide range of pulmonary fibrosis patients.
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