Lack of an Immune Response to Albunex®, a New Ultrasound Contrast Agent Based on Air-Filled Albumin Microspheres

Abstract

Albunex® is a new ultrasound contrast agent consisting of air-filled microspheres of heat-aggregated human albumin suspended in a 5% (w/v) solution of human albumin for infusion. The structural alterations induced in the albumin molecules during heat aggregation may cause the formation of new epitopes that may provoke an immunological response in recipients. To assess the possible immunogenicity of the contrast agent, 34 healthy volunteers were randomized to receive four injections of either Albunex or 5% human serum albumin (0.01 ml/kg) at 4-week intervals. Analysis of blood samples taken 3 weeks after each injection did not reveal any formation of IgE or IgG antibodies directed against the Albunex microsphere protein or albumin in any of the recipients. The evaluation of novel enzyme immunosorbent assays developed to detect the presence of these specific IgE and IgG antibodies is described. It was also investigated whether the heat-aggregated microsphere albumin was structurally altered in such a way that it could be recognized by cat albumin specific IgE, present in the sera of individuals allergic to cat albumin. 187 serum samples shown to contain elevated levels of cat albumin specific IgE were used in the study. No cross-reactive binding of the heat-aggregated human albumin to anticat albumin IgE could be detected. There is no evidence from the present studies that the heat-aggregated albumin of the Albunex microspheres will provoke an immunological reaction upon repeated injections or cause an adverse reaction when administered to allergic individuals having cat albumin as one of their allergens.

Detection of ultrasonic cavitation based on low-frequency analysis of acoustic signal

“…The same is possible to say about SonoVue R . Albunex TM , which is produced by sonication of preheated 5% albumin solution, has been tested immunologically in volunteers and no adverse reactions have been observed [5]. Chemical changes produced by sonication in echocontrast agents are not always taken into consideration.…”

Sonochemistry: Science and Engineering

“…In addition to the facile approach and indiscrimination towards agent selection, the other important feature of these sonochemically prepared microspheres is their innocuousness. Typical polymer based or chemically cross linked protein microspheres induce immune responses when subjected to the body, while sonochemically synthesized ones do not trigger any immune changes [177]. In addition to material synthesis, ultrasound is also used for many common applications such as cleansing, imaging, catalysis, plating, drug delivery etc.…”

“…[18][116] [43], [148], [177], [184], [185]. Similarly, economical and facile synthesis of graphene, carbon nanotubes, carbon nanoscrolls, and other chemical, biological materials via ultrasound have significantly simplified their processing [26][29] [25][31] [171].…”

Microbubble-Mediated Delivery for Cancer Therapy

“…Typically systemically administered, these reduce the intensity required for cavitation and other mechanical effects. Whilst many molecules and objects can act as ultrasound cavitation nuclei, the best studied and most clinically relevant types are microbubbles [77][78][79][80][81][82][83]. As microbubbles are highly echogenic, concurrent imaging can also be performed, allowing better target site recognition [84][85][86][87].…”