![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 300, Issue 3, 777-786, March 2002
Institute of Environmental Medicine and Department of Pharmacology
(J.C.M., D.W.H., V.R.M.) and Division of Pulmonary, Allergy, and
Critical Care, Department of Medicine (A.S., R.W., M.C.S., E.H.,
S.M.A.), University of Pennsylvania, Philadelphia, Pennsylvania;
Department of Pediatrics, University of Pennsylvania at the Children
Hospital of Philadelphia, Philadelphia, Pennsylvania (J.J.R.);
Departments of Cell Biology and Pharmacology, University of Pittsburgh,
Pittsburgh, Pennsylvania (S.A., S.C.W.); and Centocor, Malvern,
Pennsylvania (M.N.)
Therapeutic molecules conjugated with antibodies to the
platelet-endothelial cell adhesion molecule-1 (PECAM-1) accumulate in
the pulmonary endothelium after i.v. injection in mice. In this study,
we characterized PECAM-directed targeting to the lung and heart after
local versus systemic intravascular administration in a large animal
model, pigs. Radiolabel tracing showed that 1 h post-i.v.
injection, 35% of anti-PECAM versus 2.5% of control IgG had
accumulated in the lungs. Infusion of anti-PECAM via a catheter placed
in the right pulmonary artery (RPA) resulted in a 3-fold elevation of
the uptake in the right lower lobe and 2-fold reduction of uptake in
the left lobes in the lung. Cardiac uptake of anti-PECAM was negligible
after i.v. and RPA infusion. In contrast, delivery with a catheter
placed in the right coronary artery (RCA) resulted in a 4-fold
elevation of cardiac uptake of anti-PECAM, but not IgG, compared with
i.v. injection. To estimate the targeting of an active reporter enzyme,
streptavidin-conjugated 
-galactosidase (-Gal) was coupled to
anti-PECAM or IgG (anti-PECAM/-Gal and IgG/-Gal) and injected
into the RCA. -Gal activity was markedly elevated in the heart and
lungs (5- and 25-fold increased, respectively) after injection of
anti-PECAM/-Gal, but not IgG/-Gal. Image analysis confirmed
endothelial targeting of anti-PECAM/-Gal in the heart and lung. In
summary, anti-PECAM antibody conjugates deliver agents to the pulmonary
endothelium regardless of injection route, whereas local arterial
infusion permits targeting to the cardiac vasculature. This paradigm
may be useful for drug targeting to endothelium in lungs, heart, and
possibly other organs.
This article has been cited by other articles:
|
|
 |
|
  B.-S. Ding, N. Hong, J.-C. Murciano, K. Ganguly, C. Gottstein, M. Christofidou-Solomidou, S. M. Albelda, A. B. Fisher, D. B. Cines, and V. R. Muzykantov Prophylactic thrombolysis by thrombin-activated latent prourokinase targeted to PECAM-1 in the pulmonary vasculature Blood, February 15, 2008; 111(4): 1999 - 2006. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. V. Shuvaev, S. Tliba, M. Nakada, S. M. Albelda, and V. R. Muzykantov Platelet-Endothelial Cell Adhesion Molecule-1-Directed Endothelial Targeting of Superoxide Dismutase Alleviates Oxidative Stress Caused by Either Extracellular or Intracellular Superoxide J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 450 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Danielyan, B.-S. Ding, C. Gottstein, D. B. Cines, and V. R. Muzykantov Delivery of Anti-Platelet-Endothelial Cell Adhesion Molecule Single-Chain Variable Fragment-Urokinase Fusion Protein to the Cerebral Vasculature Lyses Arterial Clots and Attenuates Postischemic Brain Edema J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 947 - 952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-S. Ding, C. Gottstein, A. Grunow, A. Kuo, K. Ganguly, S. M. Albelda, D. B. Cines, and V. R. Muzykantov Endothelial targeting of a recombinant construct fusing a PECAM-1 single-chain variable antibody fragment (scFv) with prourokinase facilitates prophylactic thrombolysis in the pulmonary vasculature Blood, December 15, 2005; 106(13): 4191 - 4198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Christofidou-Solomidou, A. Scherpereel, R. Wiewrodt, K. Ng, T. Sweitzer, E. Arguiri, V. Shuvaev, C. C. Solomides, S. M. Albelda, and V. R. Muzykantov PECAM-directed delivery of catalase to endothelium protects against pulmonary vascular oxidative stress Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L283 - L292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-C. Murciano, S. Muro, L. Koniaris, M. Christofidou-Solomidou, D. W. Harshaw, S. M. Albelda, D. N. Granger, D. B. Cines, and V. R. Muzykantov ICAM-directed vascular immunotargeting of antithrombotic agents to the endothelial luminal surface Blood, May 15, 2003; 101(10): 3977 - 3984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Muro, R. Wiewrodt, A. Thomas, L. Koniaris, S. M. Albelda, V. R. Muzykantov, and M. Koval A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1 J. Cell Sci., April 15, 2003; 116(8): 1599 - 1609. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
