Abstract 2952: Nuclear Imaging of VCAM-1 Expression in Atherosclerosis
Vascular cell adhesion molecule-1 (VCAM-1) mediates recruitment of inflammatory cells into evolving atherosclerotic lesions. Noninvasive imaging of VCAM-1 expression may enable early detection of disease progression. Here we report the development of a VCAM-1 targeted nuclear agent based on peptide affinity ligands derived from phage display. Three agents were synthesized and tested: a cyclic peptide identified by in-vitro phage screen (VHSPNKK), derivatized with DOTA and then labeled with 111InCl3; a linear peptide identified by in-vivo phage screen in apoE-/ - mice (VHPKQHR); and a tetrameric ligand based on the latter. Agents were injected iv. in 6 age-matched apoE-/ - mice. After SPECT-CT imaging, aortas were excised, and biodistribution and autoradiography experiments were performed. The blood half life of probes was determined by repetitive retroorbital bleeding. The blood half-life of the cyclic, linear and terameric probes was 13, 16 and 16 minutes, respectively. The cyclic and the monomeric linear agents were rapidly (71% and 89% at 4 hrs) excreted via the renal route, whereas the tetrameric probe was excreted slower (11% at 4 hours). By in vivo imaging, peak SPECT activity 1 hr after injection of ~150uCi mapped to areas of high plaque load identified by CT, such as the aortic root (Figure⇓) and carotid arteries. % injected dose in apoE-/ - aortas was highest in mice injected with the tetrameric version (cyclic, 0.15%IDGT; linear, 0.07%IDGT, tetrameric, 0.36%IDGT), corroborated by autoradiography (Figure⇓). In conclusion, we developed a novel nuclear agent targeting VCAM-1, which allows for sensitive in-vivo assessment of inflammatory atherosclerotic plaques.