Seong Hoon Park MD, Presenter: Nothing to Disclose

Quan-Yu Cai MD, Abstract Co-Author: Nothing to Disclose

Kyu-Sil Choi, Abstract Co-Author: Nothing to Disclose

Su Yoen Kim, Abstract Co-Author: Nothing to Disclose

Seon-Kwan Jhung MD, PhD, Abstract Co-Author: Nothing to Disclose

Kwon-Ha Yoon MD, PhD, Abstract Co-Author: Nothing to Disclose

To investigate whether a novel, intercellular adhesion molecule-1 (ICAM-1) targeted MR agent can detect ICAM-1 expression in experimental cerebral infarction model of mice.

We designed inflammation-targeted T1 contrast agents which were prepared by bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and anti-intercellular adhesion molecule-1(ICAM-1) antibody. Photothrombotic infarction was induced in ten Balb/C mice by Rose-bengal dye (20 mg/kg) and cold light. We used a micro-MR system with 4.7T Phamascan spectrometer (Bruker Biospin, Germany). MR imaging was performed at every 6 hour from 0 to 36-hours after injection of Gd-DTPA-ICAM-1 antibody (9 nmoles of Gd/gm of body weight). The contrast agent was injected through tail vein at 12-hours after induction of brain infarction. A multislice 3D gradient echo sequence was acquired with TR/TE of 18.3/4.3 ms, and a flip angle of 30°. Immunohistochemical analysis was performed for correlation of expression of ICAM-1.

The Gd-DTPA-anti-ICAM-1 antibody displayed r1 which was two times higher than that of Gd-DTPA. In vivo MR imaging after injection of Gd-DTPA-anti-ICAM-1 antibody revealed signal enhancement in the peripheral zone of cerebral infarction in the mice model. The signal intensity of the lesion targeted anti-ICAM-1 antibody was peak at 18-hours after injection of the contrast agent and then decreased slowly. The targeted contrast agent showed significantly increased the circulation time compared with untargeted contrast agent. Immunohistochemical analysis for ICAM-1 expression in the brain tissues corresponded with the micro-MR imaging.

The Gd-DTPA-anti-ICAM-1 antibody allows noninvasive MR imaging of ICAM-1 expressing and identifies inflammatory cells in experimental cerebral infarction model of mice.

This clinically translatable agent can detect molecular process in early stage of inflammation in patients with cerebral infarction and monitor therapeutic responses.

Park, S, Cai, Q, Choi, K, Kim, S, Jhung, S, Yoon, K, MR Imaging Using Gd-DTPA-conjugated Anti-ICAM-1 Antibody in Cerebral Infarction Caused by Photochemical Thrombosis in Mice.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5015079.html