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.

Synthesis and biological evaluation of gallium-68 labelled NODAGA chelates assessing cardiac uptake and retention.

Radiolabelled lipophilic cations can be used to non-invasively report on mitochondrial dysfunction in diseases such as cardiovascular disease, cardiotoxicity and cancer. Several such lipophilic cations are currently used clinically to map myocardial perfusion using SPECT imaging. Since PET offers significant advantages over SPECT in terms of sensitivity, resolution and the capacity for dynamic imaging to allow pharmacokinetic modelling, we have synthesised and radiolabelled a series of NODAGA-based radiotracers, with triarylphosphonium-functionalisation, with gallium-68 to develop PET-compatible cationic complexes.

Detection of anthracycline-induced cardiotoxicity using perfusion-corrected Tc sestamibi SPECT.

By the time cardiotoxicity-associated cardiac dysfunction is detectable by echocardiography it is often beyond meaningful intervention. Tc-sestamibi is used clinically to image cardiac perfusion by single photon emission computed tomography (SPECT) imaging, but as a lipophilic cation its distribution is also governed by mitochondrial membrane potential (ΔΨ). Correcting scans for variations in perfusion (using a ΔΨ-independent perfusion tracer such as (bis(N-ethoxy-N-ethyldithiocarbamato)nitrido Tc(V)) (Tc-NOET) could allow Tc-sestamibi to be repurposed to specifically report on ΔΨ as a readout of evolving cardiotoxicity.