Characterization and Validation of Radiotracer Kinetics Using the Langendorff Isolated Perfused Heart

The Langendorff isolated perfused heart is a physiologically relevant and controllable ex vivo model well suited to characterizing and validating novel radiotracers for a wide range of molecular imaging applications. It allows the monitoring of first pass tracer uptake kinetics either as a bolus injection or as a continuous infusion in beating myocardial tissue with a high degree of experimental control in terms of cardiac workload, perfusion, energy substrate delivery and composition, and drug co-administration. The radiotracer pharmacokinetic data that it provides is not contaminated by confounding factors such as off-target tracer metabolism, and as a non-imaging technique, time activity curves can be acquired with very high temporal resolution. In this chapter, we describe the basic principles and practice for setting up and using Langendorff isolated perfused hearts for the assessment of novel radiotracers and outline their potential for modeling pathophysiological conditions relevant to cardiovascular disease.