Evaluation of [18F]AlF-NOTA-Octreotide PET/MRI for Characterization of Carotid Artery Atherosclerosis in Patients with Recent Stroke or Transient Ischemic Attack

The primary objective of this study is to evaluate the potential of **[18F]AlF-NOTA-octreotide PET/MRI** in characterizing and quantifying carotid atherosclerotic disease in patients who have experienced a recent stroke or transient ischemic attack (TIA). This is clinically relevant as it may provide a novel imaging modality to better understand the extent and nature of atherosclerotic disease, potentially leading to improved risk stratification and management of patients with carotid artery atherosclerosis.

Secondary objectives include determining the role of **[18F]AlF-OC PET/MRI** in identifying the risk for ipsilateral recurrent stroke in patients with recent carotid territory ischemia and ≥30% carotid artery stenosis. This could offer insights into the predictive value of this imaging technique in assessing stroke risk, thereby aiding in the prevention of recurrent cerebrovascular events.

The clinical trial focuses on patients diagnosed with **carotid artery atherosclerosis** who have experienced a recent ischemic stroke or high-risk transient ischemic attack (TIA) in the carotid artery territory. The study population includes both male and female participants aged over 18 years. Participants must have experienced a stroke or TIA no more than 21 days prior to tracer administration and have at least 30% carotid artery stenosis. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are required to have CT angiography imaging available as part of routine care. The selection criteria emphasize the importance of recent cerebrovascular events and significant carotid stenosis, ensuring the study population is relevant to the trial's objective of evaluating [18F]AlF-OC PET/MRI in characterizing and quantifying carotid atherosclerotic disease.

The clinical trial is designed as a **single-center**, prospective study to evaluate the potential of **[18F]AlF-NOTA-Octreotide** PET/MRI in characterizing and quantifying carotid atherosclerotic disease in patients with recent stroke or transient ischemic attack (TIA). The trial employs a **randomized, double-blind, controlled** methodology to ensure the reliability and validity of the results. The estimated duration of the trial is from January 1, 2025, to December 31, 2028, with participant involvement expected to last for a maximum of one day, given the nature of the **intravenous bolus injection/IV infusion** of the investigational product.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age over 18 years, recent ischemic stroke or high-risk TIA, and availability of CT angiography imaging. Following the screening, eligible participants will receive the investigational product, **[18F]AlF-NOTA-Octreotide**, administered as a solution for injection. The primary endpoint is the quantification of **[18F]AlF-OC** uptake in the culprit and non-culprit carotid artery, measured by standardized uptake value (SUV). Secondary endpoints include the predictive value of baseline plaque SUV for the recurrence of ipsilateral TIA, amaurosis fugax, and stroke over a three-year follow-up period, as well as the occurrence of any vascular complications and all-cause mortality.

The end-of-study visit will involve a final assessment to collect data on the primary and secondary endpoints. Participants may be terminated early from the study if they withdraw consent, experience adverse events, or if the investigator deems it necessary for safety reasons. The trial is categorized as a Phase II clinical trial without marketing authorization, and it is not considered a low-intervention study. The investigational product is not a pediatric formulation and is administered at a maximum daily dose of 50 micrograms, with the same amount as the total dose. The study aims to provide valuable insights into the management of carotid artery atherosclerosis in patients with recent cerebrovascular events.

The clinical trial involves the administration of the experimental medication **[18F]AlF-NOTA-Octreotide**, which is a **solution for injection**. This investigational product is designed for use in the characterization and quantification of carotid atherosclerotic disease in patients who have experienced a recent stroke or transient ischemic attack (TIA). The active substance, **[18F]AlF-NOTA-Octreotide**, is a protein-based compound. The medication is administered via **intravenous bolus injection or IV infusion**. The maximum daily dose is set at 50 micrograms, with the same limit applied to the total dose. The treatment period is restricted to a single day.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for this study. The trial is focused solely on the evaluation of the experimental medication. Participant compliance with the dosing schedule will be monitored to ensure adherence to the protocol. The study does not involve any pediatric formulations, and the investigational product is not classified as an orphan drug. The trial is conducted under the authorization of UZ Leuven, with the product's pharmaceutical form being a solution for injection.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint involves the quantification of **[18F]AlF-NOTA-Octreotide** uptake in the culprit and non-culprit carotid artery, measured by standardized uptake value (SUV). This will provide a direct assessment of the tracer's ability to characterize carotid atherosclerotic disease in patients who have experienced a recent stroke or transient ischemic attack (TIA).

Secondary endpoints will evaluate the predictive value of baseline plaque SUV for the recurrence of ipsilateral TIA, amaurosis fugax, and stroke over a three-year follow-up period. Additionally, the study will assess the recurrence of all stroke/TIA, the occurrence of any vascular complications such as myocardial infarction, cardiac arrest, hospitalization for unstable angina, or vascular death, and the occurrence of all-cause mortality. These endpoints will help determine the long-term prognostic value of the tracer in predicting vascular events and overall patient outcomes.