Clinical trial NCT06252610: PET/MRI of Primary Sclerosing Cholangitis
Official title: PET/MRI Evaluation in Patients With Primary Sclerosing Cholangitis Using Intercellular Matrix Radiopharmaceuticals
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: PSC
Keywords: PSC
[18F]-FAPI-74
[68Ga]CBP8-PET
PET/MR
Fibrosis
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2024-02-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Diagnostic accuracy in detection of fibrotic components in patients with PSC
timeFrame: (1-2 Months)
measure: Quantification of fibrotic components in PSC
timeFrame: From date of PET/MRI examination to date of final histopathology result: (max. 1-2 Months)
Secondary outcomes:
measure: Correlation of PET parameters with clinical and imaging biomarkers/tests for fibrosis
timeFrame: 1-2 Months
measure: Correlation of PET parameters with MRI parameters
timeFrame: 1-2 Months
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
state: Massachusetts
Study officials:
affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
name: Onofrio Catalano, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
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