RecruitingACTRN12622000442707

The feasibility of 18F-Fluoromisonidazole (18F-FMISO) imaging for atherosclerotic and non-atherosclerotic intra-arterial hypoxia.

The feasibility of 18F-FMISO imaging for atherosclerotic and non-atherosclerotic intra-arterial hypoxia in the setting of peripheral arterial disease requiring amputation.

Sponsor

Royal Perth Hospital

Enrollment

12 participants

Start Date

Aug 15, 2023

Study Type

Observational

Conditions

Arterial calcification Cardiovascular Disease

Summary

Cardiovascular disease remains a leading cause of death. The burden of arterial calcifications remains an important predictor of cardiovascular disease events and deaths, however, predicting those who will eventually develop a large arterial calcification burden is difficult. Recently, lab studies have suggested that a low level of oxygen within the arterial wall, and plaque, may predispose to increasing calcification in the same region. 18F-Fluoromisonidazole (18F-FMISO) Positron Emission Tomography (PET) is a novel molecular imaging modality that can detect areas of low oxygen in the arterial wall and plaque and may be a suitable imaging tool to predict where calcification develops. In a prospective arm, we aim to determine if regions of low oxygen in the vessel wall, detected with 18F-FMISO PET, in patients undergoing lower limb amputation, is associated with other markers of hypoxia (in-vitro hypoxia inducible factor 1-alpha) and calcification (ex-vivo 18F-Sodium Flouride PET) in the same anatomical region.

Eligibility

Sex: Both males and femalesMin Age: 40 Yearss

Plain Language Summary

Simplified for easier understanding

Calcification in blood vessel walls — where calcium hardens the arteries — is a major risk factor for cardiovascular events like heart attacks and strokes. But scientists have recently found that low oxygen levels within artery walls may actually trigger calcium build-up. If this can be detected early with a specialised scan before calcification develops, doctors might be able to intervene sooner. This study uses a PET imaging agent called 18F-FMISO, which 'lights up' areas of low oxygen in tissue, to scan the blood vessels of patients who are about to have a lower limb amputation due to severe arterial disease. The scan findings will be compared to markers of low oxygen and calcification measured directly in the removed tissue, helping validate whether the scan is accurate. You may be eligible if you are a male or post-menopausal female aged 40 or older who has been scheduled for a below- or above-knee amputation, and has evidence of lower limb arterial disease. People with severe lung disease requiring home oxygen, very poor kidney function, symptomatic heart failure, or certain other conditions would not be eligible.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

Participants will attend a tertiary hospital for stand-alone 18F-Fluoromisonidazole (18F-FMISO) Positron Emission Tomography Computed Tomography (PET-CT) study and a CT angiogram of the lower limbs prior to primary below-knee or above-knee amputation. PET-CT imaging will be performed for study/research purposes only. CT angiogram - Invited participants will undergo CT angiogram of the lower limbs prior to 18F-FMISO PET imaging. - The anticipated time to complete the CT angiogram is approximately 15 minutes. - Approximately 100ml of Omnipaque 350 or Optiray 350 contrast will be administered intravenously. - The procedure will be conducted by staff at the radiology department, including radiographers and radiologists. 18F-FMISO -Participants will undergo an intravenous (IV) injection of 300MBq of 18F-FMISO that will be prepared according to site protocol. -Injection of 18F-FMISO will be performed by trained nuclear medicine staff. -After the injection, participants will be rested in a quiet environment and undergo frequent oxygen saturation and heart rate monitoring, for a duration of two hours. -At two hours, 18F-FMISO PET imaging will begin with a low-dose attenuation correction CT scan of the lower limbs and the thorax. -Following this, PET imaging will be acquired in 3D list mode acquisition from toes to mid-thigh. -Subsequently, a chest imaging protocol from the upper thorax to diaphragm will be performed in prospective, cardiac gated, list mode acquisition. - PET/CT imaging will be performed over approximately 45 minutes. -18F-FMISO PET/CT is to occur up to 30 days prior to primary major limb amputation. Histological assessment -Within one hour of primary major limb amputation, lower limb arterial specimens will be salvaged to the best ability of local surgical staff. -Samples from the anterior tibial, fibular, and posterior tibial artery will be extracted and fixed according to a local protocol for histological analysis. - Samples will undergo basic histological staining and immunohistochemistry with HIF1-a. - The remaining arterial samples will be used for biomechanical testing and other imaging with ex-vivo molecular and traditional imaging modalities. Ex-vivo multi-modality imaging - Samples not used for histological analysis will undergo ex-vivo 18F-NaF PET imaging, CT imaging and computational biomechanical modeling, and ex-vivo biomechanical testing. - This will be performed after PET/CT imaging