Long-Axial Field of View (LAFOV) [18F]FDG PET/CT Imaging in Large Vessel Vasculitis (LVV): Protocol Optimisation Study. (LAVA-FLOW)
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.
Přehled studie
Postavení
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Nelze použít
Kontakty a umístění
Studijní kontakt
- Jméno: Laura J McLeavy - Clinical Trial Manager, MSc
- Telefonní číslo: 0203 313 3720
- E-mail: laura.mcleavy13@imperial.ac.uk
Studijní místa
-
-
Greater London
-
London, Greater London, Spojené království, NW3 2QG
- Royal Free London NHS Foundation Trust
-
Vrchní vyšetřovatel:
- Thomas Wagner, MBBS MSc FRCP
-
London, Greater London, Spojené království, W2 1NY
- Imperial College Healthcare NHS Trust
-
Kontakt:
- Laura J McLeavy, BSc MSc
- Telefonní číslo: 02033133720
- E-mail: laura.mcleavy13@imperial.ac.uk
-
Vrchní vyšetřovatel:
- Taryn Youngstein, BSc MB BS MD(Res) MRCP
-
Vrchní vyšetřovatel:
- Tara Barwick, MBChB MSc FRCR FRCP
-
London, Greater London, Spojené království, SE1 7EH
- King's College London
-
Kontakt:
- Sheut-Ling Lam, PhD
- E-mail: sheut-ling.1.lam@kcl.ac.uk
-
Vrchní vyšetřovatel:
- Gary Cook, MBBS MSc MD FRCR FRCP
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Základní věda
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: LVV Patients: [18F]LAFOV-PET/CT & CT Angiogram
|
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.
LVV patients will undergo a CT angiogram.
This will take place immediately after their [18F]FDG LAFOV-PET/CT.
|
|
Experimentální: Healthy Volunteers: [18F]LAFOV-PET/CT & MR Angiogram
|
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.
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.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
To investigate [18F]FDG localisation in LVV patients and HVs (controls) on LAFOV-PET/CT.
Časové okno: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes post-injection of [18F]FDG
|
SUVmax of all vascular segments in the LVV patient cohort versus the HV cohort (60-70 min p.i. data).
|
[18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes post-injection of [18F]FDG
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
To compare visual, semi-quantitative and quantitative scoring systems in LVV and HV, including smaller calibre vessels using LAFOV-PET/CT.
Časové okno: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes post-injection of [18F]FDG
|
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.
|
[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.
Časové okno: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes post-injection of [18F]FDG
|
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).
|
[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.
Časové okno: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes versus 120-130 minutes post-injection of [18F]FDG
|
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).
|
[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.
Časové okno: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes versus 120-130 minutes post-injection of [18F]FDG
|
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.).
|
[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.
Časové okno: [18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes versus 120-130 minutes post-injection of [18F]FDG
|
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.
|
[18F]FDG LAFOV-PET/CT Scan Visit - 60-70 minutes versus 120-130 minutes post-injection of [18F]FDG
|
Spolupracovníci a vyšetřovatelé
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Tara D Barwick, MBChB MSc FRCR FRCP, Imperial College Healthcare NHS Trust
- Vrchní vyšetřovatel: Taryn Youngstein, BSc MB BS MD (Res) MRCP, Imperial College Healthcare NHS Trust
Publikace a užitečné odkazy
Obecné publikace
- Slart RHJA, Glaudemans AWJM, Gheysens O, Lubberink M, Kero T, Dweck MR, Habib G, Gaemperli O, Saraste A, Gimelli A, Georgoulias P, Verberne HJ, Bucerius J, Rischpler C, Hyafil F, Erba PA; 4Is Cardiovascular Imaging: a joint initiative of the European Association of Cardiovascular Imaging (EACVI) and the European Association of Nuclear Medicine (EANM). Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation- (4Is) related cardiovascular diseases: a joint collaboration of the EACVI and the EANM: summary. Eur Heart J Cardiovasc Imaging. 2020 Dec 1;21(12):1320-1330. doi: 10.1093/ehjci/jeaa299.
- Nielsen BD, Gormsen LC, Hansen IT, Keller KK, Therkildsen P, Hauge EM. Three days of high-dose glucocorticoid treatment attenuates large-vessel 18F-FDG uptake in large-vessel giant cell arteritis but with a limited impact on diagnostic accuracy. Eur J Nucl Med Mol Imaging. 2018 Jul;45(7):1119-1128. doi: 10.1007/s00259-018-4021-4. Epub 2018 Apr 18.
- Ponte C. Classification criteria for large vessel vasculitis. ARP Rheumatol. 2024 Jul-Sep;3(3):170-173. doi: 10.63032/TIRL9893. No abstract available.
- Sari H, Eriksson L, Mingels C, Alberts I, Casey ME, Afshar-Oromieh A, Conti M, Cumming P, Shi K, Rominger A. Feasibility of using abbreviated scan protocols with population-based input functions for accurate kinetic modeling of [18F]-FDG datasets from a long axial FOV PET scanner. Eur J Nucl Med Mol Imaging. 2023 Jan;50(2):257-265. doi: 10.1007/s00259-022-05983-7. Epub 2022 Oct 4.
- Knappe L, Bregenzer C, Gozlugol N, Mingels C, Alberts I, Rominger A, Caobelli F. New thresholds in semi-quantitative [18F]FDG PET/CT are needed to assess large vessel vasculitis with long-axial field-of-view scanners. Eur J Nucl Med Mol Imaging. 2023 Nov;50(13):3890-3896. doi: 10.1007/s00259-023-06423-w. Epub 2023 Sep 7.
- Gheysens O, Jamar F, Glaudemans AWJM, Yildiz H, van der Geest KSM. Semi-Quantitative and Quantitative [18F]FDG-PET/CT Indices for Diagnosing Large Vessel Vasculitis: A Critical Review. Diagnostics (Basel). 2021 Dec 14;11(12):2355. doi: 10.3390/diagnostics11122355.
- Kang F, Han Q, Zhou X, Zheng Z, Wang S, Ma W, Zhang K, Quan Z, Yang W, Wang J, Zhu P. Performance of the PET vascular activity score (PETVAS) for qualitative and quantitative assessment of inflammatory activity in Takayasu's arteritis patients. Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3107-3117. doi: 10.1007/s00259-020-04871-2. Epub 2020 Jun 22.
- Slart RHJA; Writing group; Reviewer group; Members of EANM Cardiovascular; Members of EANM Infection & Inflammation; Members of Committees, SNMMI Cardiovascular; Members of Council, PET Interest Group; Members of ASNC; EANM Committee Coordinator. FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC. Eur J Nucl Med Mol Imaging. 2018 Jul;45(7):1250-1269. doi: 10.1007/s00259-018-3973-8. Epub 2018 Apr 11.
- Wang H, Liu Z, Shen Z, Fang L, Zhang S. Impact of coronary involvement on long-term outcomes in patients with Takayasu's arteritis. Clin Exp Rheumatol. 2020 Nov-Dec;38(6):1118-1126. Epub 2020 Feb 14.
- Rytter S, Dias AH, Munk OL, Gormsen LC. Takayasu's arteritis imaged by a LAFOV PET/CT system: better resolution leads to greater diagnostic certainty. Eur J Nucl Med Mol Imaging. 2025 Jul;52(9):3364-3365. doi: 10.1007/s00259-025-07192-4. Epub 2025 Mar 20. No abstract available.
- Rosenblum JS, Quinn KA, Rimland CA, Mehta NN, Ahlman MA, Grayson PC. Clinical Factors Associated with Time-Specific Distribution of 18F-Fluorodeoxyglucose in Large-Vessel Vasculitis. Sci Rep. 2019 Oct 23;9(1):15180. doi: 10.1038/s41598-019-51800-x.
- Dejaco C, Ramiro S, Bond M, Bosch P, Ponte C, Mackie SL, Bley TA, Blockmans D, Brolin S, Bolek EC, Cassie R, Cid MC, Molina-Collada J, Dasgupta B, Nielsen BD, De Miguel E, Direskeneli H, Duftner C, Hocevar A, Molto A, Schafer VS, Seitz L, Slart RHJA, Schmidt WA. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update. Ann Rheum Dis. 2024 May 15;83(6):741-751. doi: 10.1136/ard-2023-224543.
- van der Geest KSM, Gheysens O, Gormsen LC, Glaudemans AWJM, Tsoumpas C, Brouwer E, Nienhuis PH, van Praagh GD, Slart RHJA. Advances in PET Imaging of Large Vessel Vasculitis: An Update and Future Trends. Semin Nucl Med. 2024 Sep;54(5):753-760. doi: 10.1053/j.semnuclmed.2024.03.001. Epub 2024 Mar 27.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Cerebrovaskulární poruchy
- Onemocnění mozku
- Onemocnění centrálního nervového systému
- Nemoci nervového systému
- Cévní onemocnění
- Kardiovaskulární choroby
- Autoimunitní onemocnění
- Onemocnění imunitního systému
- Autoimunitní onemocnění nervového systému
- Kožní choroby
- Kožní onemocnění, Cévní
- Nemoci aorty
- Vaskulitida
- Vaskulitida, centrální nervový systém
- Arteritida
- Onemocnění kůže a pojivové tkáně
- Syndromy aortálního oblouku
- Obří buněčná arteritida
- Takayasuova arteritida
Další identifikační čísla studie
- EDGE 207455
- UKRI3893 (Jiné číslo grantu/financování: Medical Research Council, UK Research and Innovation)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .