Lung is the target organ for a monoclonal antibody to angiotensin-converting enzyme.
125I-labeled mouse monoclonal antibody (MoAb) to human angiotensin-converting enzyme (ACE), termed 9B9 and cross-reacting with rat and monkey ACE, when injected into the circulation, accumulates in the lung in up to 10 to 20 greater concentrations than in other organs and blood. That 111In-labeled MoAb 9B9 also accumulates in the lungs of both rats and monkeys very selectively, was clearly revealed by gamma-scintigraphy. Unlike polyclonal anti-ACE antibodies that induce an immunodependent lethal reaction when administered intravenously, MoAb 9B9 was well tolerated by rats even at very high doses (up to 300 mg/kg/body weight). At the same time, the administration of this antibody (which does not inhibit the catalytic activity of ACE) resulted in both a 3-fold decrease of the lung ACE activity and an increase in the activity of serum ACE. The highly organ-specific, nondamaging accumulation of the MoAb 9B9 makes it a promising vector for targeted drug delivery to the lung, for modeling of lung pathology, and for gamma-scintigraphic visualization of the lung vascular bed. We also suggest that MoAb 9B9 accumulation in the lung may serve as a highly sensitive marker of lung vessel damage upon various lung pathology.
Danilov
S M
SM
Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow.
Muzykantov
V R
VR
Martynov
A V
AV
Atochina
E N
EN
Sakharov IYu
Trakht
I N
IN
Smirnov
V N
VN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D003429:Cross Reactions; D000882:Haplorhini; D006801:Humans; D007074:Immunoglobulin G / Q000493:pharmacokinetics; D008168:Lung / Q000201:enzymology*; D051379:Mice; D009929:Organ Size; D007703:Peptidyl-Dipeptidase A / Q000276:immunology*; D011877:Radionuclide Imaging; D051381:Rats; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007703:Peptidyl-Dipeptidase A