Abstract 19030: Targeted Spectral Computed Tomography Molecular Imaging of Arterial Thrombus in Rabbits
Background: Although Spectral CT is still in its early clinical development stages, K-edge contrast agents designed to specifically target thrombus could provide rapid stratification of ED patients with unclear CP etiology.
Objective: To develop and demonstrate a systemically administered Spectral CT molecular imaging agent to diagnose intravascular thrombus in rabbits.
Materials: A nanocolloid (~200nm) comprised of bismuth oleate in oil (20 vol%) encapsulated with phosphatidylcholine and functionalized with an anti-fibrin peptide -PEG2000-phosphatidylethanolamine conjugate was developed (Anti-fibrin BiOL NC).
Results: Rabbits with iliac thrombus received anti-fibrin BiOL NC (1.5 ml/kg) via ear vein, which circulated for 2 hrs. The vessels were excised and imaged with a first generation Spectral CT scanner. K-edge contrast enhancement was appreciated in animals receiving anti-fibrin BiOL NC (n=4), but not in those given irrelevant-targeted BiOL NC, fibrin-targeted control nanocolloid or saline. (Figure) Optical imaging of clots in 96-well plates showed significant (p < 0.05) fibrin binding compared to irrelevant BiOL NC and anti-fibrin BiOL NC competitively inhibited an anti-fibrin antibody, NIB 1H10. Fibrin binding affinity (Kd) of the radiolabeled homing peptide was 16.1μM ± 6.5 μM. The pharmacokinetics of the vascular-targeted BiOL NC revealed a short half-life (~24 minutes) with unbound agent cleared from the blood rapidly. Biodistribution of BiOL NC was predominantly into the monocyte phagocytic system. Bismuth in sentinel organs was undetectable (< 10 ppm) within 7 days or less.
Conclusion: Anti-fibrin BiOL NC systemically target vascular thrombus in rabbits with rapid background blood clearance and bioelimination of the heavy metal. The emergence of Spectral CT contrast agents with continuing Spectral CT development promise more rapid triage of ED patients with CP.
Author Disclosures: A.H. Schmieder: None. D. Pan: None. C. Schirra: Employment; Significant; Philips Healthcare. G. Cui: None. A. Senpan: None. X. Yang: None. M.J. Scott: None. J.S. Allen: None. H. Zhang: None. A. Wang: Employment; Significant; Ocean NanoTech, LLC. S.D. Caruthers: Employment; Significant; Philips Healthcare. E. Roessl: Employment; Significant; Philips Technologie GmbH. R. Proksa: Employment; Significant; Philips Technologie GmbH. G.M. Lanza: Other Research Support; Modest; Philips Research Hamburg. Other; Modest; Ocean NanoTech, LLC has licensed WU IP.
- © 2014 by American Heart Association, Inc.