Imaging of vascular injury with 99mTc-labeled monoclonal antiplatelet antibody S12. Preliminary experience in human percutaneous transluminal angioplasty.

BACKGROUND: To evaluate the in vivo safety, biodistribution, and diagnostic accuracy of a monoclonal Fab' antibody (S12) that is specific for the platelet membrane glycoprotein (GMP-140) expressed during platelet activation at vascular injury sites, 11 peripheral percutaneous transluminal angioplasty (PTA) patients (age, 61 +/- 8 years) with severe vascular disease had serial 99mTcS12 radionuclide imaging at 5 and 90 minutes, 4-6 hours, and 20-24 hours after a total of 23 angiographically successful PTA procedures. No acute allergic reactions or hematologic toxicity occurred. METHODS AND RESULTS: The average PTA percent angiographic diameter stenosis (DS) at all 23 sites decreased from 85 +/- 12% to 12 +/- 11%, with a mean before-to-after-PTA change of 73 +/- 14% (p less than 0.01). The mean radionuclide image-derived ratio of 99mTc S12 activity in PTA versus contralateral non-PTA arterial segments for all angioplasty sites was 1.6 +/- 0.5. Vascular 99mTc S12 antibody activity was qualitatively evident in the majority (78%) of PTA sites at 4-6 hours after injection. 99mTc S12 target-to-background (muscle) ratio equaled 2.3 +/- 0.6 at PTA sites. Nine PTA sites (39%) had residual 99mTc S12 activity at 24 hours after injection (mean PTA site-to-contralateral artery ratio, 1.5 +/- 0.4). The mean vascular 99mTc S12 activity ratios in 10 procedurally complicated (defined as extensive dilation [greater than 2 cm] or grade I or greater arterial dissection) and 13 uncomplicated PTA segments were 1.9 +/- 0.5 versus 1.2 +/- 0.1, respectively (p less than 0.01). The associated before-to-after-PTA angiographic improvement was significantly less in procedurally complicated PTA sites (66 +/- 12% versus 80 +/- 12% DS; p less than 0.01). CONCLUSIONS: 99mTc S12 activity is significantly increased at angiographically patent PTA sites that are procedurally complicated and are associated with less significant before-to-after-PTA angiographic improvement. 99mTc S12 monoclonal Fab' antibody imaging permits noninvasive identification of local vascular platelet activation resulting from angioplasty balloon injury in humans.

Aortic bifurcation stenosis: treatment with intravascular stents.

Balloon-expandable intravascular stents were employed to correct atherosclerotic stenosis of the aortic bifurcation. The devices were placed in the proximal iliac arteries with the cephalic end of the stents contacting in the midline. This arrangement provided an adequate lumen for the distal portion of the aortic wall and the proximal iliac arteries. Six of seven patients who received this form of treatment had hemodynamic and clinical improvement of their vascular insufficiency at an average follow-up of 1 year.

In vivo technetium-99m S12 antibody imaging of platelet alpha-granules in rabbit endothelial neointimal proliferation after angioplasty.

To examine the specificity of technetium-99m monoclonal antibody (S12) imaging for identifying activated platelets at interventional injury sites in atherosclerotic rabbit arteries, subgroups of unheparinized rabbits (n = 39) underwent serial percutaneous transluminal aortic angioplasty (PTA) procedures (with or without intravascular stent placement) followed by in vivo and then ex vivo gamma camera imaging, scanning, and immunoelectron microscopy to determine the intravascular loci of S12 Fab' antibody binding. Despite angiographic vessel patency, image-derived ratios of in vivo S12 binding in injured versus uninjured vascular segments were significantly increased (p less than 0.05) after one PTA (1.3 +/- 0.17, n = 7), PTA twice at 6-week intervals (1.4 +/- 0.22, n = 7), and PTA plus stent placement (1.6 +/- 0.28, n = 7) compared with control experiments (1.1 +/- 0.13, n = 7). Ex vivo imaging of blood-free excised aortas confirmed S12 localization at PTA (2 +/- 0.4, n = 3) and PTA plus stent placement (5 +/- 3.8, n = 7) sites (both p less than 0.05 versus controls). S12 antibody uptake decreased significantly (p less than 0.05) at 1 week after PTA plus stent placement in vivo (1.1 +/- 0.10, n = 4) and ex vivo (1.6 +/- 0.7, n = 3). Electron microscopic studies confirmed dense platelet, fibrin, and red blood cell deposition in regions of acute injury, with endothelial neointimal proliferation at 1 week after PTA. Immunoelectron microscopic studies confirmed specific in vivo S12 binding (22:1 versus nonrelevant IgG) at sites of alpha-granule GMP-140 expression in activated platelets. Therefore, S12 studies may be useful to localize sites of platelet-derived mitogen release at arterial PTA injury sites.

Placement of balloon-expandable intraluminal stents in iliac arteries: first 171 procedures.

Balloon-expandable intraluminal stents were used to treat iliac artery stenoses or occlusions that failed to respond to conventional balloon angioplasty. One hundred seventy-one procedures were performed in 154 patients, of whom 48 had a limb at risk for amputation. Thirty-six had severe and 70 had moderate intermittent claudication. At the latest follow-up examination (average, 6 months; range, 1-24 months), 137 patients demonstrated clinical benefit, 113 of whom had become asymptomatic. Eleven patients showed no initial benefit, and six improved initially but later developed new vascular symptoms. Complications occurred in 18 patients. In three patients, complications were directly related to the device. Two occlusions were successfully recanalized, and an intramural collection of contrast material secondary to balloon perforation evolved favorably. The remaining patients had groin hematoma (n = 6), distal embolization (n = 4), extravasation (n = 2), transient renal failure (n = 1), pseudoaneurysm at the puncture site (n = 1), or subintimal dissection (n = 1). All stents have remained patent to the latest follow-up examination without evidence of migration or aneurysm formation.

Evaluation of polymer-coated balloon-expandable stents in bile ducts.

The long-term patency of and biologic response to the presence of polymer-coated balloon-expandable intraluminal stents in the bile ducts was studied in 18 dogs. Metallic stents coated with two different polymers (silicone rubber and segmented polyether-polyurethane) were placed in 12 dogs and uncoated stents in six, and animals were killed after 4, 12, and 24 weeks of observation. Cholangiograms were obtained at 1, 4, 6, 12, and 24 weeks, depending on length of follow-up. All bile duct segments containing stents remained patent throughout the follow-up periods. Characteristic luminal narrowings due to hyperplastic papillary mucosa occurred with all three stent types. although no difference could be found in the degree of narrowing of the most restrictive segment among the three stent types, mucosal proliferation was most extensive with the uncoated stent. Lack of concretion buildup and benign tissue response encourage the development of a clinically useful expandable biliary endoprosthesis.