Targeting arterial wall sulfated glycosaminoglycans in rabbit atherosclerosis with a mouse/human chimeric antibody.

Abstract

The progression of atherosclerosis is favored by increasing amounts of chondroitin sulfate proteoglycans in the artery wall. We previously reported the reactivity of chP3R99 monoclonal antibody (mAb) with sulfated glycosaminoglycans and its association with the anti-atherogenic properties displayed. Now, we evaluated the accumulation of this mAb in atherosclerotic lesions and its potential use as a probe for specific in vivo detection of the disease. Atherosclerosis was induced in NZW rabbits (n = 14) by the administration of Lipofundin 20% using PBS-receiving animals as control (n = 8). Accumulation of chP3R99 mAb in atherosclerotic lesions was assessed either by immunofluorescence detection of human IgG in fresh-frozen sections of aorta, or by immunoscintigraphy followed by biodistribution of the radiotracer upon administration of (99m)Tc-chP3R99 mAb. Immunofluorescence studies revealed the presence of chP3R99 mAb in atherosclerotic lesions 24 h after intravenous administration, whereas planar images showed an evident accumulation of (99m)Tc-chP3R99 mAb in atherosclerotic rabbit carotids. Accordingly, (99m)Tc-chP3R99 mAb uptake by lesioned aortic arch and thoracic segment was increased 5.6-fold over controls and it was 3.9-folds higher in carotids, in agreement with immunoscintigrams. Moreover, the deposition of (99m)Tc-chP3R99 mAb in the artery wall was associated both with the presence and size of the lesions in the different portions of evaluated arteries and was greater than in non-targeted organs. In conclusion, chP3R99 mAb preferentially accumulates in arterial atherosclerotic lesions supporting the potential use of this anti-glycosaminoglycans antibody for diagnosis and treatment of atherosclerosis.

• Authors: Yosdel Soto, Niurka Mesa, Yumisley Alfonso, Arlenis Pérez, Fernando Batlle, Tania Griñán, Adonis Pino, Justo Viera, Milagros Frómeta, Victor Brito, Armando Olivera, Francisco Zayas, Ana M Vázquez
• Journal: mAbs (MAbs) Vol. 6 Issue 5 Pg. 1340-6 ( 2014) ISSN: 1942-0870 [Electronic] United States
• PMID: 25517318 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Drug Combinations
• Glycosaminoglycans
• Organotechnetium Compounds
• Phospholipids
• Recombinant Fusion Proteins
• Sulfates
• Lipofundin
• Sorbitol
• Technetium

Topics

• Administration, Intravenous
• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacokinetics, pharmacology)
• Aorta (drug effects, metabolism, pathology)
• Atherosclerosis (chemically induced, drug therapy, metabolism)
• Drug Combinations
• Fluorescent Antibody Technique
• Glycosaminoglycans (antagonists & inhibitors, metabolism)
• Humans
• Male
• Mice
• Organotechnetium Compounds
• Phospholipids
• Rabbits
• Radioimmunodetection (methods)
• Recombinant Fusion Proteins (administration & dosage, pharmacokinetics, pharmacology)
• Sorbitol
• Sulfates (metabolism)
• Technetium
• Time Factors
• Tissue Distribution