PET Imaging of MMP Activation in AAA: Clinical Component

Overview

A first-in-human evaluation of \[64Cu\]-RYM2 with PET/CT will be performed to: a) assess its safety, biodistribution, and radiation dosimetry in normal volunteers (WU) and; b) in AAA patients undergoing surgery (WU and Yale), evaluate radiotracer pharmacodynamics and correlate PET imaging characteristics (WU) with ex vivo tissue measurements (Yale).

Detailed description

A first-in-human evaluation of \[64Cu\]-RYM2 with PET/CT will be performed to: a) assess its safety, biodistribution, and radiation dosimetry in normal volunteers (WU) and; b) in AAA patients undergoing surgery (WU and Yale), evaluate radiotracer pharmacodynamics and correlate PET imaging characteristics (WU) with ex vivo tissue measurements (Yale).

Interventions

• Drug Cu-64-RYM2
  PET/CT scan
• Drug PET imaging using Cu-64
  PET/CT at different timepoints

Primary outcome measures

• Verification Cu-64RYM2-2 signal in AAA segments. This will be performed by measuring Standard Uptake Values obtained from analysis of the Cu-64RYM2 images, in AAA patients. [Time frame: 2 years]

Secondary outcome measures (1)

• Cu-64RYM-2 signal is higher [Time frame: 2 years]

Eligibility criteria

Inclusion Criteria: Healthy Volunteers

• No history of claustrophobia or other preventing condition that has previously or would interfere with completion of protocol-specified imaging sessions.
• Able to comprehend and willing to follow instructions for the study procedures as called for by the protocol.
• Capable of lying still and supine within the PET/CT scanner for \~1 hour and follow instructions for breathing protocol during the CT portion.
• No illicit drug use or other inhaled drug use (including pharmacologic agents, recreational agents, or illicit drugs) within the past year.
• No known history of cardiac, pulmonary, hepatic or renal disease or diabetes
• BMI ≤ 40

Exclusion Criteria: Healthy Volunteers

• Inability to receive and sign informed consent;
• Pregnant (confirmed by urine pregnancy test) and/or breastfeeding
• Patient with chronic renal disease whose glomerular filtration rate (GFR) is less than 30 mL/min/1.73 m2
• Patients with an unstable clinical condition that in the opinion of the principal investigators or designee precludes participation in the study.
• Is deemed likely to be unable to perform all research procedures for any reason, (e.g., subjects unable to lie still or inability to tolerate up to 60 minutes in a supine position with arms up during the PET imaging procedures due to chronic back/shoulder pain or arthritis as assessed by physical examination and medical history).
• Currently using recreational drugs.
• Body weight of >300 lbs. (weight limit of the PET table).
• Currently enrolled in another study using an investigational drug or underwent a study the last year involving investigational use of radiotracers or CT would confound results or with a radiation exposure when combined with this study would be deemed as excessive by the Sponsor-Investigator.

Inclusion Criteria: Patients with AAA electively or semi-electively scheduled for surgical repair

• Men or women 40-80 years of age
• Willing and able to provide informed consent
• Medically managed hypertension and hyperlipidemia
• No history of claustrophobia or other preventing condition that has previously or would interfere with completion of protocol-specified imaging sessions
• Able to comprehend and willing to follow instructions for the study procedures as called for by the protocol
• Patients with AAA indicated for surgical repair (5.0 \[female\] - 5.5cm \[male\]), incidentally identified large(r) AAAs (>5.5 or 6.0 cm), and rapidly expanding AAAs (> 0.5 cm in 6 months or > 1 cm in 12 months) per Guidelines of the Society for Vascular Surgery.

Exclusion Criteria: Patients with AAA electively or semi-electively scheduled for surgical repair

• Inability to receive and sign informed consent.
• Currently enrolled in another study using an investigational drug
• Pregnant (confirmed by urine pregnancy test) and/or breastfeeding
• Patient with chronic renal disease whose GFR is less than 30 mL/min/1.73 m2
• Documented allergy to iodinated contrast and/or shellfish
• Patients with an unstable clinical condition that in the opinion of the principal investigators or designee precludes participation in the study.
• Inability to tolerate 60 minutes in a supine position with arms down at sides, as necessary for PET/CT.
• Other conditions such as symptomatic/recently treated coronary disease, cancer requiring oncologic management, or autoimmune/inflammatory diseases (e.g., rheumatoid arthritis or multiple sclerosis).
• Non-AAA volunteers may not carry a diagnosis of aortoiliac occlusive disease, as documented by their treating vascular surgeon, as significantly progressed atherosclerotic disease may demonstrate exaggerated, associated MMP activity.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• Washington University School of Medicine — St Louis

Publications

• Zhang J, Nie L, Razavian M, Ahmed M, Dobrucki LW, Asadi A, Edwards DS, Azure M, Sinusas AJ, Sadeghi MM. Molecular imaging of activated matrix metalloproteinases in vascular remodeling. Circulation. 2008 Nov 4;118(19):1953-60. doi: 10.1161/CIRCULATIONAHA.108.789743. Epub 2008 Oct 20. PMID 18936327
• Davis FM, Rateri DL, Daugherty A. Abdominal aortic aneurysm: novel mechanisms and therapies. Curr Opin Cardiol. 2015 Nov;30(6):566-73. doi: 10.1097/HCO.0000000000000216. PMID 26352243
• Curci JA, Beckman JA. Positron Emission Tomography Fluorine-18-Labeled 2-Deoxy-2-Fluoro-d-Glucose Tells a Complicated Story in the Aortic Aneurysm Wall. Circ Cardiovasc Imaging. 2016 Nov;9(11):e005689. doi: 10.1161/CIRCIMAGING.116.005689. No abstract available. PMID 27903546
• Golestani R, Sadeghi MM. Emergence of molecular imaging of aortic aneurysm: implications for risk stratification and management. J Nucl Cardiol. 2014 Apr;21(2):251-67; quiz 268-70. doi: 10.1007/s12350-013-9845-5. Epub 2014 Jan 1. PMID 24381115
• Kent KC. Clinical practice. Abdominal aortic aneurysms. N Engl J Med. 2014 Nov 27;371(22):2101-8. doi: 10.1056/NEJMcp1401430. No abstract available. PMID 25427112
• Davis FM, Rateri DL, Daugherty A. Mechanisms of aortic aneurysm formation: translating preclinical studies into clinical therapies. Heart. 2014 Oct;100(19):1498-505. doi: 10.1136/heartjnl-2014-305648. Epub 2014 Jul 24. PMID 25060754
• Toczek J, Meadows JL, Sadeghi MM. Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification. Circ Cardiovasc Imaging. 2016 Jan;9(1):e003023. doi: 10.1161/CIRCIMAGING.115.003023. PMID 26763279

Identifiers

NCT: NCT07473102 · 202505027

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗