PT  - JOURNAL ARTICLE
AU  - Arnaud Scherpereel
AU  - Jonathan J. Rome
AU  - Rainer Wiewrodt
AU  - Simon C. Watkins
AU  - David Winslow Harshaw
AU  - Sean Alder
AU  - Melpo Christofidou-Solomidou
AU  - Elliott Haut
AU  - Juan-Carlos Murciano
AU  - Marian Nakada
AU  - Steven M. Albelda
AU  - Vladimir R. Muzykantov
TI  - Platelet-Endothelial Cell Adhesion Molecule-1-Directed Immunotargeting to Cardiopulmonary Vasculature
AID  - 10.1124/jpet.300.3.777
DP  - 2002 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 777--786
VI  - 300
IP  - 3
4099  - http://jpet.aspetjournals.org/content/300/3/777.short
4100  - http://jpet.aspetjournals.org/content/300/3/777.full
SO  - J Pharmacol Exp Ther2002 Mar 01; 300
AB  - 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 β-galactosidase (β-Gal) was coupled to anti-PECAM or IgG (anti-PECAM/β-Gal and IgG/β-Gal) and injected into the RCA. β-Gal activity was markedly elevated in the heart and lungs (5- and 25-fold increased, respectively) after injection of anti-PECAM/β-Gal, but not IgG/β-Gal. Image analysis confirmed endothelial targeting of anti-PECAM/β-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. The American Society for Pharmacology and Experimental Therapeutics