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.
Royal Perth Hospital
12 participants
Aug 15, 2023
Observational
Conditions
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
Inclusion Criteria2
- Male or post-menopausal female (defined as the absence of menses of >12 months in the absence of pathology) above the age 40 who have undergone a clinical decision to proceed to below knee or above knee amputation
- Have evidence of arterial disease on a prior lower limb computed-tomography angiography, X-ray, or have clinical suspicion of lower limb arterial disease.
Exclusion Criteria12
- Inability to provide informed consent
- A diagnosis of chronic obstructive pulmonary disease or other respiratory disease that currently requires home oxygen therapy
- A resting oxygen saturation (measured at time of screening and in the absence of oxygen therapy) below 92%
- eGFR less than or equal to 40 at time of screening
- Symptomatic heart failure impairing an ability to lie flat on for imaging purposes or requiring supplemental oxygen therapy
- A prior below knee, above knee or higher, lower limb amputation of the other limb
- Acute lower limb ischemia requiring urgent revascularisation or emergent amputation
- Prior orthopaedic surgery of the lower limb with foreign material remaining in-situ
- In-patients requiring nurse escort for inter-hospital transport
- Recent or current lung cancer or cancer of the lower limb (excluding Non-melanoma skin cancer)
- Known cardiac arrhythmia that precludes ECG gating
- Known or suspected allergy to iodine contrat
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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
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ACTRN12622000442707