Application of Cardiac Molecular Imaging Using Positron Emission Tomography in Evaluation of Drug and Therapeutics for Cardiovascular Disorders

Abstract

The incidence of cardiovascular disease is increasing with the aging population. This has stimulated a need for innovative means to evaluate and develop therapeutic strategies intended to improve patient care. Positron emission tomography (PET) imaging is an advanced nuclear imaging technology. The advantage of PET over other non-invasive imaging modalities is its ability to accurately measure tissue concentrations of specific radiolabeled compounds. These radioligands can be used as molecular probes to quantify physiological processes and the effects of therapy. Molecular imaging with PET has been applied to evaluate new and established drugs and therapies, as well as their effects on physiological parameters. New radiolabeled receptor ligands will also allow in vivo pharmacokinetic studies following drug treatment, yielding insights into drug delivery, optimal drug occupancy, and mechanism of action at the receptor level. These exciting tissue pharmacokinetic data could revolutionize evaluation of drug therapies in cardiovascular diseases. In addition, serial evaluations of these processes are now possible in both animals and humans permitting sensitive means to evaluate disease progression and therapies. New tools for imaging such as PET/CT and small animal PET broaden the potential of PET in drug evaluation. This review will describe the accuracy of PET as a non-invasive modality to quantify various parameters, and the application of PET in evaluating new and established therapies. This paper will also review the application of receptor ligand imaging and the principles of using surrogate physiological end-points in early drug development and evaluation.

Quantitative analysis of coronary endothelial function with generator-produced 82Rb PET: comparison with 15O-labelled water PET

“…We have demonstrated coronary endothelial dysfunction in young smokers otherwise no coronary risk factors testing using 15 O-water PET and CPT [13] . We also assessed the effects of therapeutic interventions in patients with hypertension using 15 O-water PET and CPT [4].…”

“…Each subject underwent rest and CPT imaging with both 15 O-water and 82 Rb PET. The 15 O-water and 82 Rb imaging were performed in randomized order (mean interval 17.6 ± 13.1 days).…”

“…We also assessed the effects of therapeutic interventions in patients with hypertension using 15 O-water PET and CPT [4]. In most previous studies, PET MBF measurements have been performed using either 15 O-water or 13 N-ammonia, which require immediate access to an on-site cyclotron [14][15].…”

“…Rubidium-82 ( 82 Rb) is a PET perfusion tracer produced from a strontium-82 ( 82 Sr)/ 82 Rb generator and is widely used in PET centers without immediate access to a cyclotron for the diagnosis of coronary artery disease [15][16]. Thus, it is possible to apply 82 Rb perfusion studies in larger populations [17][18].…”

“…However, there are limited data reported on MBF quantification using 82 Rb [19][20][21][22][23], and to our knowledge there has been no published data evaluating the MBF response during CPT to measure coronary endothelial function. The purpose of the current study was to develop coronary endothelial function measurements using 82 Rb, evaluate MBF response during CPT in smokers, and compare these results to those observed using 15 O-water PET.…”