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

Abstract

Background— Positron-emission tomography (PET) tracers for myocardial perfusion are commonly labeled with short-lived isotopes that limit their widespread clinical use. 18 F-BMS-747158-02 ( 18 F-BMS) is a novel pyridaben derivative that was evaluated for assessment of myocardial perfusion by comparison with 13 N-ammonia ( 13 NH 3 ) and with radioactive microspheres in a pig model. Methods and Results— Fourteen pigs injected with 500 MBq of 13 NH 3 or 100 to 200 MBq of 18 F-BMS underwent dynamic PET at rest and during pharmacological stress. In 8 of these pigs, 18 F-BMS was injected during stress combined with transient, 2.5-minute constriction of the left anterior descending coronary artery. Radioactive microspheres were coinjected with 18 F-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 13 NH 3 , 18 F-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 18 F-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 18 F-BMS and microspheres also correlated closely ( r =0.63, slope=1.1). Conclusions— 18 F-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 18 F renders this tracer useful for clinical PET/CT applications in the workup of patients with suspected or proven coronary artery disease.

Simplified Quantification of Myocardial Flow Reserve with flurpiridaz F 18: Validation with Microspheres in a Pig Model

“…Thus, extraction is higher for flurpiridaz F 18 than for the currently used SPECT and PET tracers. flurpiridaz F 18 is also an interesting alternative because its half-life (110 min) is longer than that of the conventional PET tracers, making it potentially suitable for MBF and MFR quantification in the clinical setting (21,22,30,36).…”

“…The PET images were analyzed using MunichHeart software (developed at Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München), which has been previously validated for flurpiridaz F 18 PET quantitative analyses (22).…”

“…Image Quantification: Uptake, MBF, and Retention flurpiridaz F 18-derived MBF (at rest and stress) was quantitatively analyzed using a 3-compartment tracer kinetic model as shown previously (22). In short, since the single-pass extraction fraction of flurpiridaz F 18 is high (0.94) and almost unchanged at high flow rates (30), no correction terms for a flow-dependent extraction were used.…”

“…This means that MBF can be measured reliably with a kinetic model even at high flow rates and that the image quality is excellent (20)(21)(22). We hypothesize that high extraction and the long tissue half-life of this tracer allow for quantitative analysis of MBF using a simplified analysis, which would be easier to introduce into the clinical routine.…”

An isolated perfused pig heart model for the development, validation and translation of novel cardiovascular magnetic resonance techniques

“…Graded ischaemia [19], ischaemic preconditioning [20] and the coronary microcirculation [21] have all been studied in different porcine models. In vivo imaging in pig models has previously been used to study coronary blood-flow using coloured microspheres [22], microvascular function using computer tomography (CT) [23], and to validate novel perfusion tracers for positron emission tomography (PET) [24]. Other applications include validation of MR-guided real time coronary catheterization or percutaneous transluminal balloon angioplasty in aortic coarctation [25,26].…”