Long-Axial Field of View (LAFOV) [18F]FDG PET/CT Imaging in Large Vessel Vasculitis (LVV): Protocol Optimisation Study.

N/ANot Yet RecruitingNCT07628075

Imperial College London18 enrolled

Overview

Large vessel vasculitis (LVV) is an autoimmune inflammatory disorder affecting the major arteries of the body. The diagnosis and monitoring this condition can be challenging, as patients often present with symptoms that are unclear, and the diagnostic criteria currently used are varied. Accurate diagnosis is essential because it helps to tailor the treatment to each patient. Some treatments, such as steroids and immunosuppressive medications, can have significant side effects, so they need to be used carefully and only when truly needed. An \[18F\]FDG Positron Emission Tomography/Computed Tomography (PET/CT) involves the injection of a small amount of radiolabelled sugar, which assesses glucose metabolism within the body. \[18F\]FDG PET/CT is already used by the NHS to detect inflammation within the vessel walls and diagnose LVV. Current diagnostic criteria for LVV largely rely on visual assessment by a radiologist. This approach therefore has limitations and may not fully capture changes in the levels of inflammation over time. A new generation of scanners, known as Long Axial Field-of-View (LAFOV)-PET/CT or Total Body PET, are currently transforming what is possible in the field of medical imaging. These LAFOV-PET/CT scanners have new digital detectors that are more sensitive, produce sharper images, and can scan the entire body rapidly. This offers several potential advantages for patients with LVV, including the clearer detection of vessel wall inflammation, the ability to administer lower doses of the radiolabelled sugar (\[18F\]FDG), and the ability to take repeated pictures over time to measure subtle changes in blood flow and inflammation. Patients receiving a routine NHS \[18F\]FDG PET/CT scan for LVV are typically scanned 60 minutes after injection of the radiotracer using a standard PET/CT. Another benefit of LAFOV-PET/CT scanners is their ability to assess the amount of the radiolabelled sugar taken up by the whole body almost as soon as it is injected which could give important additional information. As part of the LAVA-FLOW study we are planning to combine LAFOV-PET/CT with a CT Angiogram (CTA) in patients with LVV. A CTA is a scan that shows doctors what your blood vessels look like. It involves the injection of a dye into a vein that makes your blood vessels visible, highlighting vessel wall inflammation and vessel wall narrowing. This combination of LAFOV-PET/CT and CTA therefore has the potential to give a much more detailed picture of LVV than is achievable using current methods. The LAVA-FLOW study therefore aims to develop a standardised protocol to be used in different hospital centres across the UK for the imaging of LVV using LAFOV-PET/CT. We also hope that the results of this particular study could lead to further larger studies with the potential to update the diagnostic criteria and improve the monitoring of this condition.

Systemic vasculitidies are autoimmune diseases which cause inflammation of blood vessels and are categorised according to the size of blood vessels they predominantly involve. The main forms of LVV are giant cell arteritis (GCA) and Takayasu arteritis (TA). Various imaging modalities are available for the diagnosis of large vessel vasculitis (LVV): ultrasound, magnetic resonance angiography (MRA), computed tomography angiography (CTA) and \[18F\]fluorodeoxyglucose (\[18F\]FDG) PET/CT. Whilst \[18F\]FDG PET/CT is established in the diagnostic work up of LVV, the relatively low spatial resolution, radiation exposure, and long imaging times have limited its use especially for assessing smaller calibre vessels and coronary arteries. Digital long-axial field of view (LAFOV)-PET/CT systems are expected to significantly improve the diagnosis and management of LVV, as their increased sensitivity allows for improved detection of the involvement of smaller calibre vessels and low-grade inflammation, even at shorter scan times and/or reduced tracer doses. LAFOV-PET/CT has the potential to perform dynamic whole-body imaging from the time of radiotracer injection for detailed analysis of \[18F\]FDG uptake. Additionally, there is the opportunity to acquire LAFOV-PET/CT images and combine this approach with CT angiogram imaging of the heart and all large vessels within one sitting. At present, determining the involvement of small vessels currently relies on the treating physician requesting a CT angiogram (CTA) in addition to other imaging investigations at diagnosis, which is not currently common practice. A combined protocol of \[18F\]FDG LAFOV-PET/CT and CTA performed that could be performed at diagnosis and during follow-up may allow the burden of coronary artery disease in this cohort to be fully established and to better define its natural history on treatment. For follow-up response cases, particularly in TA, the potential for using lower radiation does with LAFOV-PET/CT is important to further develop the use of PET/CT in these cohort for surveillance monitoring. The current European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) guidelines for assessment of LVV on \[18F\]FDG PET/CT recommend visual interpretation of static images using a 4-point visual scale. Although visual analysis of static \[18F\]FDG PET/CT data is currently clinically recommended for LVV cases. this has limitations. The improved spatial resolution of LAFOV-PET/CT could lead to higher vessel identification through the use of semi-quantitative analysis methods. The improved spatial resolution of LAFOV-PET/CT could lead to higher vessel identification and the potential misdiagnosis of LVV in normal vessels compared to standard PET/CT. We will therefore need to consider the use of different thresholds when using LAFOV-PET/CT. In addition to collecting data from patients diagnosed with LVV, data from healthy volunteers (HV) will help us to establish normal background vessel activity on LAFOV-PET/CT. The HV cohort shall have MR angiography (MRA) instead of CTA to keep radiation doses as low as possible. This study will establish a protocol for LAFOV-PET/CT imaging and provide pilot data for a larger study, which may lead to changing the current visual reporting criteria for LVV by establishing new reference ranges for disease activity. LAVA-FLOW aims to establish an \[18F\]FDG LAFOV-PET/CT protocol utilising both dynamic and static imaging in combination with angiography.

Interventions

[18F]FDG Long-Axial Field of View (LAFOV)-PET/CTDIAGNOSTIC_TEST

All participants will undergo an initial standard dose attenuation correction CT (ACCT) scan. \[18F\]FDG will be administered with a target injected dose of 1.5MBq/kg at 0 minutes in a single IV bolus. The participants will undergo a dynamic LAFOV-PET/CT scan between 0-55 minutes. This will be followed by a 10-minute cardiac-gated static PET/CT scan performed between 60-70 minutes post-injection. A further ACCT (standard dose ACCT for LVV patients \& low dose ACCT for healthy volunteers) followed by delayed static LAFOV-PET/CT will subsequently be performed at +120 minutes post-injection for up to 10 minutes.

CT AngiogramDIAGNOSTIC_TEST

LVV patients will undergo a CT angiogram. This will take place immediately after their \[18F\]FDG LAFOV-PET/CT.

MR AngiogramDIAGNOSTIC_TEST

Healthy Volunteers will have an MR angiogram at Imperial College Healthcare NHS Trust. This scan visit will be performed on a separate date following the performance of their LAFOV-PET/CT.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria LVV Patients: * ≥18 years of age * Newly diagnosed LVV (based on the 2022 American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR) classification criteria or from a definite diagnosis of LVV on standard of care imaging) * WHO performance status 0-2 * The subject is able and willing to comply with study procedures and signed and dated informed consent is obtained * eGFR of ≥30 (mL/min/1.73m2) within 3 months of \[18F\]FDG injection in subjects who have a history of renal impairment, renal disease, renal transplant or diabetes Exclusion Criteria LVV Patients: * The subject is pregnant or lactating * Participants with claustrophobia or who are unable to comfortably tolerate the scanning procedure * History of allergy to iodinated contrast * Commencement of steroids \> 7 days prior to administration of the radiotracer * Poorly controlled diabetic with a blood glucose \>11mmol/L * Evidence of a significant medical condition or laboratory finding which, in the opinion of the Investigator, makes it undesirable for the patient to participate in the trial. Inclusion Criteria Healthy Volunteers: * Three subjects ≥18 years of age that are also \< 50 years old and three subjects ≥50 years of age * WHO performance status 0-2 * The subject is able and willing to comply with study procedures and signed and dated informed consent is obtained Exclusion Criteria Healthy Volunteers: * The subject is pregnant or lactating * Participants with claustrophobia or who are unable to comfortably tolerate the scanning procedure * Participants with any contra-indication to MRI * Known allergy to gadolinium-based contrast agents * History of smoking * History or current diagnosis of the following medical conditions: * Diabetes Mellitus * Chronic Kidney Disease * Atrial Fibrillation * Migraines * Rheumatoid Arthritis * Systemic Lupus Erythematosus (SLE) * Historic or current prescription of the following medications: * Any blood pressure medication * Any antipsychotic medication * Steroids * Weight of ≥75Kg (in order to keep the radiation dose \<10mSV for HV) * Evidence of any significant medical condition which, in the opinion of the Investigator, makes it undesirable for the HV to participate in the trial * Participants that have undergone any imaging investigation that exposes them to radiation within the previous 12 months

Outcomes

Primary Outcomes

To investigate [18F]FDG localisation in LVV patients and HVs (controls) on LAFOV-PET/CT.

SUVmax of all vascular segments in the LVV patient cohort versus the HV cohort (60-70 min p.i. data).

Time frame: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes post-injection of [18F]FDG

Secondary Outcomes

To compare visual, semi-quantitative and quantitative scoring systems in LVV and HV, including smaller calibre vessels using LAFOV-PET/CT.

Summary comparison of visual (PETVAS scoring), semi-quantitative (SUVmax, SUVmean \& tissue to background ratio (TBR) and SUV/TBR) and quantitative (Ki Patlak analysis) scoring systems at 60-70 min p.i.

Time frame: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes post-injection of [18F]FDG

To investigate how simulated lower dose acquisitions affect vascular activity and scan quality on LAFOV-PET/CT.

Visual scoring (PETVAS scoring - most diseased and summed vascular segments), and semi-quantitative scoring (SUVmax and TBR) on image data (at 60-70 min p.i.) reconstructed using shorter acquisition times (1, 2, 4, 6, 8 and 10 min).

Time frame: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes post-injection of [18F]FDG

To assess the impact of using the CT angiogram (CTA) for attenuation correction in LVV patients on LAFOV-PET/CT.

Summary comparison of visual (PETVAS scoring) and semi-quantitative (SUVmax, SUVmean and TBR) using CTA or attenuation correction CT (ACCT) for the purpose of attenuation correction of the 120-130 min p.i. data (120-130 min static) and 60-70 min p.i. data (60-70 min static).

Time frame: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes versus 120-130 minutes post-injection of [18F]FDG

To investigate the impact of delayed imaging at 120-minute post-injection on vascular activity on LAFOV-PET/CT.

Summary comparison of visual (PETVAS scoring), semi-quantitative (SUVmax, SUVmean , TBR and SUV/TBR) and quantitative (Ki Patlak analysis) scoring systems at multiple acquisition time points (60-70 min compared to 120-130 min p.i.).

Time frame: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes versus 120-130 minutes post-injection of [18F]FDG

To establish normal background FDG uptake in HV controls on LAFOV-PET/CT.

Summary statistics including confidence intervals of visual (PETVAS scoring) and semi-quantitative (SUVmax, SUVmean , TBR and SUV/TBR) scoring at 60-70 and 120-130 min p.i.

Time frame: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes versus 120-130 minutes post-injection of [18F]FDG

Long-Axial Field of View (LAFOV) [18F]FDG PET/CT Imaging in Large Vessel Vasculitis (LVV): Protocol Optimisation Study.

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts