Abstract 16389: Molecular Imaging of Vulnerable Plaque With Thrombus-Specific NanoQ Copper Nanocolloids
Introduction: Sensitive detection of ruptured plaque, the sine qua non of stroke and myocardial infarction, remains an unmet challenge. Previous gadolinium-peptide conjugates lacked clinical efficacy and posed a risk for Nephrogenic Systemic Fibrosis.
Objective: The objective was to develop and characterize the first molecular imaging (MI) agent for fibrin based on copper-based nanocolloids.
Methods: Nanocolloids of copper (Cu) (NanoQ) were synthesized (Dav=217 nm, ζ=−13mV) and characterized for MI of thrombus. MR properties of NanoQ in suspension were defined at 3.0 T at 25C followed by MR imaging of fibrin clots with NanoQ or a control (n=3/group) using fibrin-specific antibodies (NIB5F3). In vivo pharmacokinetics and 24 hour biodistribution, and bioelimination of NanoQ was evaluated in rodents.
Results: The particulate relaxivity of the NanoQ was high, r1=66,000±2200 (s•mmol [NanoQ])−1, while the ionic r1 relaxivitiy (4.3±0.1 (s•mmol [Cu])−1) was similar to Gd-DTPA. The particulate r2 relaxivities were r2=135,000±2900 and ionic r2 relaxivities of 10.4±0.34 (s•mmol [Cu])−1, respectively. NanoQ targeted to fibrin clot phantoms provided strong contrast enhancement (400%, p<0.05), while control clots (non-targeted and targeted no metal) had no signal enhancement. NanoQ given i.v. had a long half-life (100 min, n=3), determined by fitting two-compartment bi-exponential model fit (R2>0.99). Twenty-four hours post injection approximately 90% of the metal was eliminated from the animal with the residual copper measured in the feces, liver, and kidney.
Conclusions: Fibrin-specific NanoQ is a novel, high relaxivity, non-gadolinium, MI agent that could afford sensitive noninvasive MR imaging of thrombus associated with ruptured plaques in high risk patients.
- Magnetic resonance imaging
- Myocardial infarction
- Vulnerable plaque
- Contrast media
- Noninvasive cardiac imaging
- © 2011 by American Heart Association, Inc.