Targeted Transport of 125I-Labeled Antibody to GFAP and AMVB1 in an Experimental Rat Model of C6 Glioma

Abstract

Glioblastoma is the most common high-grade glioma characterized by strikingly poor therapeutic outcome with survival time of about a year. This makes a search for new therapeutic approaches to glioblastoma treatment an area of great clinical importance. The present study aims to explore the potential of targeted delivery of 125I-radiolabeled antibodies, specific to glial fibrillary acidic protein (GFAP) and AMVB1 (antigen of abluminal membrane of endotheliocytes predominantly expressed in glioblastoma microvessels) as a strategy for in vivo tumor targeting. Rat C6 glioma model was used to test this hypothesis. Tumor bearing animals, injected with radiolabeled monoclonal antibodies to GFAP or AMVB1, were compared to control group, which received nonspecific mouse IgG. Radioactivity of blood, brain hemispheres, and some other tissues was measured 6, 24, 48, 72, and 96 h posttreatment. Our results demonstrate accumulation of both types of antibodies in tumors. Concentrations of both antibodies were significantly increased in tumor-bearing hemisphere compared to intact hemisphere. Antibodies to GFAP specifically accumulated in brain and bound tumor tissue with the high affinity. In contrast, increased accumulation of anti-AMVB1 antibody was detected in antigen-expressing organs, such as spleen and kidney. Based on results presented, we propose that the monoclonal antibodies to GFAP can be used as vectors for the delivery of diagnostic and pharmacological agents to high-grade gliomas. Development of this strategy would open new clinical perspectives for glioblastoma diagnostics and therapy.

Visualization of Connexin 43-positive cells of glioma and the periglioma zone by means of intravenously injected monoclonal antibodies

“…This was more than 50-times higher than the radioactivity of the normal brain tissue and almost 5-times higher than accumulation of non-specific mouse IgG in the tumor under the same conditions. In the experiments with injection of 125 I-labeled MAbE2Cx43, the specific radioactivity of the glioma bearing hemisphere exceeded the radioactivity measured in our earlier study where rats with glioma were injected with 125 I-labeled monoclonal antibodies against GFAP (Chekhonin et al, 2009).…”

“…in the case of surgical resection. Since reactive astrocytes and astroblasts accompany all these areas (Chekhonin et al, 2009), their visualization would allow clear differentiation between the glioma invasion area and normal tissue. Second, recent studies have shown that the glioma invasion is the most active in the peritumoral zone.…”

Immunofluorescent Analysis of Connexin-43 Using Monoclonal Antibodies to Its Extracellular Domain

“…Purifi ed from ascitic fl uid, these monoclonal antibodies were used for immunohistochemical analysis on sections of the rat brain with experimental C6 glioma. It is known that its development is associated with an intense astroglial reaction around the tumor at all stages of its development [4,5], while GFAP-positive reactive astrocytes can produce Cx43 in high amounts [16].…”

Vegfrs in Neoplastic Angiogenesis and Prospects for Therapy Оf Brain Tumors

“…Эти особенности могут быть использованы для селективного транспор-та наноразмерных систем в малигнизированную ткань. В связи с этим принципиально новым направлением может стать внедрение контейнерных систем на основе антител для высокоселективного направленного транс-порта лекарственных средств [101][102][103][104][105].…”