PET/MRI of Primary Sclerosing Cholangitis

PSC Clinical Trial

Official title: PET/MRI Evaluation in Patients With Primary Sclerosing Cholangitis Using Intercellular Matrix Radiopharmaceuticals

Status Not yet recruiting

Clinical Trial Summary

This study aims to use positron emission tomography (PET)/magnetic resonance imaging (MRI) to diagnose and quantify PSC-related biliary tract fibrosis and to improve upon the currently available non-invasive diagnostic capabilities by investigating the ability of combined PET/MRI to detect and quantify fibrosis using a novel collagen-binding radiotracer. Specifically, the investigators will be comparing [68Ga]CBP8- and [18F]-FAPI-74 PET/MRI to a liver transient elastography scan in the diagnosis of biliary tree fibrosis.

Clinical Trial Description

Imaging in the form of cholangiography plays an essential role in diagnosing and managing PSC. In the past decade, magnetic resonance cholangiopancreatography (MRCP) has become preferred over endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of PSC because it is non-invasive, thereby safer, and cheaper than ERCP. MRCP's sensitivity and specificity for diagnosing PSC are high, 86% and 94%, respectively. However, to quantify liver fibrosis, MRCP is only accurate in more advanced stages of the disease. Intrahepatic biliary stricture severity was a poor discriminator between the different grades of liver fibrosis measured on magnetic resonance elastography and the different risk strata according to the Mayo Risk Score and The Amsterdam-Oxford prognostic index (AOPI). Other non-invasive diagnostic tests, such as transient elastography, lack full-organ evaluation and may be subject to variation between measurements, despite being the current gold standard for non-invasive fibrosis quantification.

This study aims to use [68Ga]CBP8- or [18F]FAPI PET/MRI to diagnose and quantify PSC-related biliary tract fibrosis. The novel radiopharmaceutical collagen-binding probe 8 labeled with Gallium-68 selectively binds to collagen type I, the predominant extracellular protein in fibrosis. [68Ga]CBP8 has already been investigated in patients affected by pulmonary fibrosis with success. Fibroblast activation protein (FAP) is a type II transmembrane serine protease that is overexpressed in CAFs and, to a lesser extent, in benign processes. It is associated with extracellular matrix remodeling, for example, chronic inflammation, degenerative bone and spine disease, arthritis, and cardiac remodelling after myocardial infarction. Quinolone-based FAP inhibitors (FAPIs) constitute a class of molecules with high affinity to FAP deployed to assess many types of solid tumors and some benign pathologies. 68Ga-FAPIs and, to a lesser extent, 18F-FAPI are being extensively studied in oncologic and non-oncologic positron emission tomography/computed tomography (PET/CT) and, to a lesser extent, PET/MRI, both in Europe and Asia.

In this open-label, single-arm, single-center prospective study, the investigators will recruit 10 patients with known primary sclerosing cholangitis (PSC) who have previously undergone other modalities for the evaluation of hepatic fibrosis, such as liver biopsy and/or transient elastography (FibroScan) and/or MR liver elastography and/or US liver elastography.No healthy volunteers will be included. Patients will be referred to [68Ga]CBP8 or [18F]-FAPI-74 PET/MRI by their primary treating physicians (e.g., hepatologist). After a phone-call pre-screening, electronic medical records verification, and a screening visit, subjects will be imaged with [68Ga]CBP8 or [18F]-FAPI-74 PET/MRI. A blood draw might also be performed to measure serum biomarkers of liver fibrosis.

Transient liver elastography has a diagnostic accuracy ranging from 65% in the initial stages to 90% for severe fibrosis in the setting of PSC. There is no data regarding the use of [68Ga]CBP8 PET/MRI to diagnose or quantify fibrosis in PSC. Therefore, the investigators lack sufficient evidence to estimate power with a reasonable degree of certainty. By enrolling 10 patients for this initial pilot study in the evaluation of hepatic/biliary fibrosis with [68Ga]CBP8 PET/MRI, the investigators will be able to acquire enough data to determine the optimal sample size for a larger study. A paired McNemar's test will be used for hypothesis testing regarding differences in sensitivity, specificity, accuracy, negative predictive value, and positive predictive value between [68Ga]CBP8 PET/MRI and FibroScan. Moreover, the investigators will analyze quantitative features of PET (SUV) and obtain their correlation to the actual fibrosis as reported by the gold standard test. These will be performed using Spearman's correlation coefficient and regression analysis. ;

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• PSC

• NCT number: NCT06252610
• Study type: Observational
• Source: Massachusetts General Hospital
• Contact: Onofrio Catalano, MD, Ph.D
• Phone: 617-724-4030
• Email: ocatalano@mgh.harvard.edu
• Status: Not yet recruiting
• Start date: April 10, 2024
• Completion date: April 30, 2026