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(Circulation. 2009;119:2333-2342.)
© 2009 American Heart Association, Inc.

Imaging

Evaluation of the Novel Myocardial Perfusion Positron-Emission Tomography Tracer ¹⁸F-BMS-747158-02

Comparison to ¹³N-Ammonia and Validation With Microspheres in a Pig Model

S.G. Nekolla, PhD; S. Reder, RT; A. Saraste, MD; T. Higuchi, MD; G. Dzewas, RT; A. Preissel, DVM; M. Huisman, PhD; T. Poethko, PhD; T. Schuster, MSc; M. Yu, PhD; S. Robinson, PhD; D. Casebier, PhD; J. Henke, DVM; H.J. Wester, PhD; M. Schwaiger, MD

From Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München (S.G.N., S.R., A.S., T.H., G.D., M.H., T.P., H.J.W., M.S.), München, Germany; Zentrum für Präklinische Forschung der Technischen Universität München (A.P., J.H.), München, Germany; Institut für medizinische Statistik und Epidemiologie der Technischen Universität München (T.S.), München, Germany; and Departments of Discovery Chemistry and Discovery Biology (M.Y., D.C.), Lantheus Medical Imaging, North Billerica, Mass.

Correspondence to Stephan G. Nekolla, PhD, Nuklearmedizinische Klinik der Technischen Universität München, Ismaningerstrasse 22, D-81675 München, Germany.

Received June 11, 2008; accepted January 30, 2009.

Background— Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. ¹⁸F-BMS-747158-02 (¹⁸F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with ¹³N-ammonia (¹³NH₃) and with radioactive microspheres in a pig model.

Methods and Results— Fourteen pigs injected with 500 MBq of ¹³NH₃ or 100 to 200 MBq of ¹⁸F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, ¹⁸F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with ¹⁸F-BMS. Ratios of myocardial tracer uptake to surrounding tissues were determined, and myocardial blood flow was quantified by compartmental modeling. Both tracers showed high and homogeneous myocardial uptake. Compared with ¹³NH₃, ¹⁸F-BMS showed higher activity ratios between myocardium and blood (rest 2.5 versus 4.1; stress 2.1 versus 5.8), liver (rest 1.2 versus 1.8; stress 0.7 versus 2.0), and lungs (rest 2.5 versus 4.2; stress 2.9 versus 6.4). Regional myocardial blood flow assessed with ¹⁸F-BMS PET showed good correlation (r=0.88, slope=0.84) and agreement (mean difference –0.10 [25th percentile –0.3, 75th percentile 0.1 mL · min^–1 · g^–1]) with that measured with radioactive microspheres over a flow range from 0.1 to 3.0 mL · min^–1 · g^–1. The extent of defects induced by left anterior descending coronary artery constriction measured by ¹⁸F-BMS and microspheres also correlated closely (r=0.63, slope=1.1).

Conclusions— ¹⁸F-BMS-747158-02 is a very attractive new PET perfusion tracer that allows quantitative assessment of regional myocardial perfusion over a wide flow range. The long half-life of ¹⁸F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

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