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(Circulation. 2003;108:1310.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Phase I Drug and Light Dose-Escalation Trial of Motexafin Lutetium and Far Red Light Activation (Phototherapy) in Subjects With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention and Stent Deployment

Procedural and Long-Term Results

Dean J. Kereiakes, MD; Arthur M. Szyniszewski, MD; Dennis Wahr, MD; Howard C. Herrmann, MD; Daniel I. Simon, MD; Campbell Rogers, MD; Paul Kramer, MD; Wendy Shear, MD; Alan C. Yeung, MD; Kendrick A. Shunk, MD, PhD; Tony M. Chou, MD; Jeffrey Popma, MD; Peter Fitzgerald, MD; Tanya E. Carroll, BS; David Forer, MS; Daniel C. Adelman, MD

From The Lindner Center and Ohio Heart Health Center (D.J.K.), Cincinnati, Ohio; Michigan Heart & Vascular (A.M.S., D.W.), Ypsilanti, Mich; University of Pennsylvania Medical Center (H.C.H.), Philadelphia, Pa; Interventional Cardiology (D.I.S.) and Division of Cardiovascular Diseases (J.P.), Brigham & Women’s Hospital (C.R.), Boston, Mass; Harvard-MIT Division of Health Sciences and Technology (C.R.), Cambridge, Mass; Mid-America Heart Institute (P.K.), Kansas City, Mo; University of Minnesota (W.S.), Minneapolis, Minn; Stanford University Medical Center (A.C.Y., P.F.), Stanford, Calif; University of California (K.A.S., T.M.C.), San Francisco, Calif; and Pharmacyclics, Inc (T.E.C., D.F., D.C.A.), Sunnyvale, Calif.

Correspondence to Dean J. Kereiakes, MD, The Lindner Center for Research & Education, 2123 Auburn Ave, Suite 424, Cincinnati, OH 45219. E-mail lindner{at}fuse.net

Received February 7, 2003; de novo received April 21, 2003; revision received June 23, 2003; accepted June 24, 2003.

Background— Motexafin lutetium (MLu; Antrin) is a photosensitizer that is taken up by atherosclerotic plaque and concentrated within macrophages and vascular smooth muscle cells. After photoactivation with far red light, MLu facilitates production of cytotoxic oxygen radicals that mediate apoptosis. We assessed the safety and tolerability of phototherapy (PT) with MLu in patients undergoing percutaneous coronary intervention with stent deployment.

Methods and Results— An open-label, phase I, drug and light dose-escalation clinical trial of MLu PT enrolled 80 patients undergoing de novo coronary stent deployment. MLu was administered to 79 patients by intravenous infusion 18 to 24 hours before procedure, and photoactivation was performed after balloon predilatation and before stent deployment. Clinical evaluation, serial quantitative angiography, and intravascular ultrasound were performed periprocedurally and at 6 months follow-up. MLu PT was well tolerated without serious dose-limiting toxicities, and side effects (paresthesia and rash) were minor. No adverse angiographic outcomes were attributed to phototherapy.

Conclusions— This study demonstrates that coronary MLu PT seems safe, and the maximum well-tolerated MLu dose and range of tolerated light doses were identified. These data can be used in phase II efficacy trials of MLu PT for the treatment of coronary atherosclerosis or vulnerable plaque.

Key Words: motexafin lutetium • phototherapy • atherosclerosis • restenosis

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