PET/MRI of Primary Sclerosing Cholangitis

February 9, 2024 updated by: Onofrio A. Catalano, MD, PhD, Massachusetts General Hospital

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Observational

Enrollment (Estimated)

10

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Charlestown, Massachusetts, United States, 02129
        • Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

In total, 10 subjects with PSC fulfilling the inclusion criteria will be recruited. All subjects recruited for the study will be able to withdraw from the study at any time. The patients will be referred to the study by their treating physicians to investigate liver or biliary tract fibrosis in the setting of PSC.

Description

Inclusion Criteria:

  • Established clinical diagnosis of large duct PSC
  • Participants receiving treatment for IBD are allowed if on a stable dose from screening and expected to remain stable for the duration of the study
  • Serum AST and ALT concentration ≤ 8 times the upper limit of normal

Exclusion Criteria:

  • Other causes of chronic liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically
  • Known or suspected overlapping clinical or histologic diagnosis of autoimmune hepatitis
  • Subjects less than 18 years of age or greater than 85 years of age.
  • Subjects with electrical implants, such as cardiac pacemakers or perfusion pumps.
  • Subjects with ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, prosthetic heart valves that are not compatible with the gradient maps of our scanners, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing.
  • Subjects who anticipate being pregnant or breastfeeding (a negative STAT quantitative serum hCG pregnancy test is required on the day of the scan before the subject can participate).
  • Subjects with claustrophobic reactions
  • Subjects with more significant than average potential for cardiac arrest.
  • Subjects with a history of major head trauma (i.e., multiple concussions, traumatic brain injury).
  • Subjects with a history of bleeding disorders.
  • Subjects whose research-related radiation exposure exceeds current Radiology Department guidelines (i.e., 50 mSv in the prior 12 months).
  • Subjects unable to lie comfortably on a bed inside the PET/MRI bore as assessed by physical examination and medical history (e.g., back pain, arthritis).
  • Subjects under the direct supervision of the principal investigator;
  • Subjects with a body weight of > 300 lbs (operational weight limit of the PET/MRI table) or BMI >33 kg/m2 (the Athinoula A. Martinos Center standard procedure to avoid claustrophobia or mechanical impossibility of fitting the subject into the scanner bore, which is less than 60 cm wide).
  • A history of acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2
  • Perioperative liver transplantation period.
  • A history of systemic lupus, multiple myeloma, nephrogenic systemic fibrosis, or other comorbidities resulting in chronic kidney disease stage IV or higher

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PSC
Population will be consecutive patients with PSC, who will be referred to us by the MGB-affiliated hepatologists.
Drug: Radiotracer Injection

An intravenous catheter will be placed in an arm or hand vein for injection of [68Ga]CBP8;

  • 6-10 mCi of [68Ga]CBP8 or 5-9 mCi of FAPI will be injected into the Biograph mMR system. The injected dose and the time of injection will be recorded;
  • The catheter will be flushed with 0.9% saline solution;
  • The subjects will then be positioned on the scanner table; support devices under the back or legs will be used to enable the patient to maintain his/her position throughout the scan comfortably.
Drug: Contrast Media, Magnetic Resonance

The same intravenous catheter used to inject the radiotracer will be used to inject the hepatospecific gadolinium contrast agent Eovist (Bayer, Whippany, NJ);

  • After being positioned on the PET/MRI table, the nuclear medicine technologist will connect the patient to the MRI-safe power injector;
  • The catheter will be flushed before and after injection with 0.9% saline solution;
  • About halfway through the imaging session, the study staff will inform the patient that they are going to be administering the contrast agent and what sensations they should and should not expect;
  • The contrast will then be injected.
Diagnostic test: Imaging

MRI and PET scanner to be used:

3.0 T Laboratory (Bay 7) Siemens Biograph mMR.

Magnetic resonance images of the abdomen will be acquired using the Martinos Center's combined 3 Tesla PET/MRI scanner. The image quality on these 3 Tesla devices will be very high, equivalent to or better than any other standard clinical MRI system. PET images of the target body site will be acquired When necessary, the data acquisition will be started shortly before radiotracer injection; Coincidence event data will be acquired and stored in list mode or compressed (i.e., sinogram space) format. Subjects will be asked to lie still for the duration of the study. The entire imaging session will last up to 120 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic accuracy in detection of fibrotic components in patients with PSC
Time Frame: (1-2 Months)
To establish the diagnostic capabilities (sensitivity, specificity, accuracy) of PET/MRI using [68Ga]CBP8 or [18F]-FAPI-74 for detection of the fibrotic component in patients with PSC.
(1-2 Months)
Quantification of fibrotic components in PSC
Time Frame: From date of PET/MRI examination to date of final histopathology result: (max. 1-2 Months)
Quantification of fibrotic component in patients with PSC with [68Ga]CBP8- or [18F]-FAPI-74-PET/MT by using liver histology (when available) as the standard for comparison. If histology is unavailable, non-invasive tests (FibroScan, MRI Elastography, serum biomarkers) will be used.
From date of PET/MRI examination to date of final histopathology result: (max. 1-2 Months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation of PET parameters with MRI parameters
Time Frame: 1-2 Months
Compare fibrosis levels with gadoxetate contrast-enhanced and other MRI parameters (e.g., MRCP)
1-2 Months
Correlation of PET parameters with clinical and imaging biomarkers/tests for fibrosis
Time Frame: 1-2 Months
Compare fibrosis levels as measured by [68Ga]CBP8 or [18F]FAPI-74-PET/MRI to selected fibrosis plasma biomarkers, fibroscan, and derived scores.
1-2 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Onofrio Catalano, MD, Ph.D, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 10, 2024

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

April 30, 2026

Study Registration Dates

First Submitted

February 2, 2024

First Submitted That Met QC Criteria

February 2, 2024

First Posted (Actual)

February 9, 2024

Study Record Updates

Last Update Posted (Actual)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 9, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022P002225

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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