None listed
Conditions
Brief summary
This pilot study aims to leverage the novel imaging capabilities available at the Australian National Total Body PET Facility to identify peripheral nerve amyloidosis in populations with amyloidosis due to either AL or ATTR with the typical length dependent neuropathy, proximal nerve involvement, small and autonomic neuropathy alone and in populations of ATTRwt with neuropathy not explained by alternate causes. We will evaluate for differences in uptake which could differentiate patients with AL versus ATTR amyloidosis and assess for direct nerve infiltration in ATTRwt. We will evaluate Florbetaben uptake in organs and compare this to routine organ screening investigations, and will aim to quantify previously difficult to identify muscle and tenosynovial uptake. Finally, we will explore the feasibility of generating a global amyloid burden score to provide a quantitative measure of whole-body amyloid load, which would have potential to be used in future clinical trials of amyloid depleters.
Interventions
This pilot study is a cross-sectional study to evaluate the utility of [18F] Florbetaben-PET to evaluate peripheral nerve and whole-body amyloid uptake.
Whole-body [18F]Florbetaben PET-CT scans will be performed in 25 individuals (20 participants and 5 healthy controls) recruited from Westmead and St Vincent’s Amyloidosis Centres. Five patients will be recruited for each amyloid neuropathy pattern, including: Length-dependent large fibre neuropathy, Plexopathy or Mononeuritis multiplex, Isola
This pilot study is a cross-sectional study to evaluate the utility of [18F] Florbetaben-PET to evaluate peripheral nerve and whole-body amyloid uptake. Whole-body [18F]Florbetaben PET-CT scans will be performed in 25 individuals (20 participants and 5 healthy controls) recruited from Westmead and St Vincent’s Amyloidosis Centres. Five patients will be recruited for each amyloid neuropathy pattern, including: Length-dependent large fibre neuropathy, Plexopathy or Mononeuritis multiplex, Isolated small fibre and autonomic neuropathy and wildtype tranthyretin amyloidosis (ATTRwt) with neuropathy, not explained by an alternate aetiology. The five healthy controls will be recruited from family members of participants attending appointments at the Amyloidosis Centre, and staff from each Amyloidosis centres. Participants will be phenotyped including evaluation of their clinical history, examination findings, investigations, and both clinical and organ staging, as part of their routine clinical care. This routine testing includes clinical staging scores, examination, blood testing, echocardiogram, cardiac bone-scintigraphy and nerve conduction studies. All participants will visit the Australian National Total Body PET Facility for a single whole-body [18F] Florbetaben PET/CT scan. Standard clinical procedures will be followed using the Siemens Biograph Vision Quadra PET/CT scanner. The imaging agent, [18F]Florbetaben (150 ± 10% MBq), will be administered by a radiologist or radiographer as a bolus intravenous injection 90 minutes prior to imaging to allow for maximum specific binding to amyloid deposits and achieve optimal signal-to-background ratio. Following injection, participants will rest in a quiet uptake room. After the 90-minute uptake period, they will be positioned supine on the scanning bed, instructed to remain still and breathe normally. A low-dose CT scan (120 kVp, Qref 40 mAs intensity modulation with DoseCare4D) will be performed for anatomical localization and attenuation correction of the PET data. Following the CT scan, a short 10-minute whole-body PET acquisition will be performed. Post scan care will include removal of the intravenous cannula. Participants will be checked to ensure they are not adversely affected.
Sponsors
University of Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Diagnosis
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria Interventional group: 1. Adults between 18 and 90 years of age 2. Confirmed or suspected light chain (AL) or transthyretin (TTR) amyloidosis, meeting diagnostic criteria for one of the following categories: a. Length-dependent large fibre neuropathy b. Plexopathy or Mononeuritis multiplex c. Isolated small fibre and autonomic neuropathy d. ATTR wildtype (ATTRwt) with neuropathy, not explained by an alternate aetiology 3. Willingness to provide written informed consent and willingness to participate and comply with the study requirements. Inclusion criteria control group: 1. Adults between 18 and 90 years of age 2. No evidence of neuropathy 3. Willingness to provide written informed consent and willingness to participate and comply with the study requirements
Exclusion criteria
Exclusion criteria for Intervention and control groups: 1. Pre-existing neuropathy of alternate aetiology 2. Significant renal or hepatic impairment that may affect tracer metabolism and clearance. 3. Use of investigational anti-amyloid therapies within the past 6 months. 4. Unstable cardiovascular disease, including recent myocardial infarction (=6 months) or uncontrolled arrhythmias. 5. Active malignancy or history of cancer requiring treatment within the past 6 months 6. Active systemic infection or inflammatory disease that could cause non-specific tracer uptake. 7. Severe claustrophobia or inability to remain supine for imaging. 8. Pregnancy or breastfeeding 9. Body weight exceeding scanner limitations (>200 kg). 10. Recent chemotherapy or radiation therapy (<6 weeks prior to imaging) that may alter amyloid burden. 11. Inability to provide informed consent or cognitive impairment affecting study participation. 12. History of severe psychiatric illness that may interfere with study compliance.
Outcome results
None listed