Magnetic resonance imaging of radiation-induced brain injury using targeted microparticles of iron oxide

Abstract

Radiation-induced brain injury (RBI) is the most serious complication of primary and metastatic brain and neck malignant tumors following radiation therapy. However, at present, RBI is difficult to diagnose in the early period. Recently, studies have demonstrated that the early stage of RBI is characterized by an inflammatory reaction, and that intercellular adhesion molecule-1 (ICAM-1) is significantly up-regulated in the irradiated brain tissues. To provide an early diagnosis of RBI using molecular magnetic resonance imaging (MRI) with microparticles of iron oxide (MPIO) targeted to ICAM-1 in the vascular endothelium of brains. A monoclonal antibody against ICAM-1 was conjugated to MPIO to form the targeted MRI contrast agent ICAM-MPIO. The adhesion of ICAM-MPIO to endothelial cells was quantified by optical imaging and MRI. Sprague-Dawley rats were irradiated to establish an animal model of the early period of RBI. ICAM-MPIO and free-MPIO were injected via tail vein, respectively. T(2) signal intensity and T(2) values of the irradiated brains and normal brains were subsequently evaluated by MRI. In vitro, the adhesion of ICAM-MPIO to the activated endothelial cells was 5 ± 0.5-fold greater than to the non-stimulated cells, which could be detected by optical imaging and MRI (R(2) = 1.0, P < 0.01). In vivo, ICAM-MPIO caused a marked negative MRI contrast effect in irradiated brains. As compared with brains without irradiation, the specific contrast effect increased more than seven-fold after administration of ICAM-MPIO (F = 751.495, P < 0.05). MPIO coated with monoclonal antibody of ICAM-1 could be used for detecting the early period of RBI by optical imaging and MRI.