Immunoliposomes for detection of rupture-prone intracranial aneurysms

Abstract

Background: It is estimated that significant (3.2%) of population carries intracranial aneurysm (IA). An increasing number of imaging studies have caused that the chance of finding an incidental aneurysm is becoming more common. Since IA rupture causes subarachnoidal hemorrhage (SAH) and have significant mortality and morbidity prophylactic treatment should be considered when IA is detected. The benefit and risk of treatment of IA is based on epidemiological estimate which takes account patient and aneurysm characteristics. However we know that aneurysm rupture is biological process where inflammation of aneurysm wall is actively leading to degeneration of aneurysm wall and finally weakens it until it bursts. Until now, there have not been imaging method to detect inflammatory process of aneurysm wall METHODS: We created targeting immunoliposome for use in the imaging of aneurysm. Immunoliposome comprises antibodies against at least one vascular inflammatory marker associated with aneurysm inflammation and a label and/or a contrast agent.

Results: Histological analysis of IAs where immunoliposome comprises antibodies against vascular inflammation with a label shows promising results for selectively detecting aneurysms inflammation. In magnetic resonance imaging (MRI) we were able to detect immunoliposomes carrying gadolinium.

Conclusion: Our work opens a new avenue for using contrast labeled immunoliposomes for detecting rupture-prone aneurysms. Immunoliposomes can cary gadolinium and selectively bind to inflammatory section of aneurysm that can be detected with MRI. Further research is needed to develop immunoliposomes to be used with MRI in humans to target treatment to those patients who benefit from it the most.

Keywords: Cerebral aneurysm; Imaging; Inflammation; Intracranial aneurysm; Liposome; Subarachnoid hemorrhage.

Fig. 1

Stainings on tonsil (A–D) or intracranial aneurysm (E–F) for aSMA- or CD31-conjugated immunoliposomes and unconjugated control liposomes, where, in each panel, the first image shows the immunostaining for antibody (green), the second image shows rhodamine-conjugated lipids (red), and the last image merges the channels with staining for DAPI (blue) for nuclei

Fig. 2

Stainings for aSMA- or CD31-conjugated immunoliposomes and unconjugated control liposomes on cultured smooth muscle cells (A–B) and endothelial cells (C–D), where, in each panel, the first image shows the immunostaining for antibody (green), the second image shows rhodamine-conjugated lipids (red), and the last image merges the channels with staining for DAPI (blue) for nuclei

Fig. 3

MRI (3 Tesla) of gadolinium-containing immunoliposomes at different concentrations in vitro with T1 sequence seen as white area in phantom, and control (tap water) seen as grey (star)