In vivo uptake of radiolabeled antibody to proliferating smooth muscle cells in a swine model of coronary stent restenosis.
Z2D3 is a monoclonal chimeric antibody fragment that is directed against a protein expressed on the surface of proliferating smooth muscle cells. The purpose of this study was to investigate the uptake of 111In-labeled Z2D3 F(ab')2 in a swine model of coronary neointimal proliferation after overexpansion coronary stenting.


METHODS
Twenty-two domestic swine underwent overexpansion coronary stenting of 2 vessels. Fifteen swine survived 2-4 wk, at which time they received an injection of 111In Z2D3 F(ab')2 and underwent planar imaging. After the swine were killed, the hearts were excised and imaged on the detector. The cross-sectional area of each stented vessel was measured with digital morphometry.


RESULTS
Pathology could be correlated with imaging for 24 vessels. The cross-sectional area of stenosis comprising neointimal proliferation ranged from 8% to 95%, with a mean +/- SD of 41% +/- 21%. The maximal stenosis ranged from 13% to 95%, with a mean of 51% +/- 20%. Seventeen of 24 vessels (71%) showed focal uptake on in vivo imaging, and 7 of 24 (29%) did not. Twenty of 24 (83%) showed uptake on ex vivo imaging. Of 11 stented vessels with maximal vessel stenosis less than 50%, 7 (64%) showed uptake both in vivo and ex vivo, and of 13 stented vessels with maximal vessel stenosis greater than 50%, 10 (77%) showed uptake both in vivo and ex vivo.


CONCLUSIONS
Uptake of a radiolabeled antibody directed against a component of proliferating neointimal tissue can be visualized in the coronary arteries on in vivo imaging using a scintillation gamma camera.
Johnson
L L
LL
Department of Medicine, Rhode Island Hospital, Providence 02903, USA.
Schofield
L M
LM
Verdesca
S A
SA
Sharaf
B L
BL
Jones
R M
RM
Virmani
R
R
Khaw
B A
BA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology; D002455:Cell Division; D003327:Coronary Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology*; D007074:Immunoglobulin G / Q000494:pharmacology; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D011475:Prosthesis Failure; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C116410:indium 111-cT84.66 monoclonal antibody