Application of cardiac molecular imaging using positron emission tomography in evaluation of drug and therapeutics for cardiovascular disorders.
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.
Yoshinaga
Keiichiro
K
National Cardiac PET Centre, University of Ottawa Heart Institute, Ontario, Canada.
Chow
Benjamin J W
BJ
dekemp
Robert A
RA
Thorn
Stephanie
S
Ruddy
Terrence D
TD
Davies
Ross A
RA
DaSilva
Jean N
JN
Beanlands
Rob
R
D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003952:Diagnostic Imaging; D004353:Drug Evaluation, Preclinical; D015316:Genetic Therapy; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism; D049268:Positron-Emission Tomography; D011956:Receptors, Cell Surface / Q000378:metabolism; D013312:Stress, Physiological / Q000503:physiopathology
D002317:Cardiovascular Agents; D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface