PET Imaging of MMP Activation in AAA: Clinical Component

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).

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.