Cardiac Radionuclide Imaging in Rodents: A Review of Methods, Results, and Factors at Play

Abstract

The interest around small-animal cardiac radionuclide imaging is growing as rodent models can be manipulated to allow the simulation of human diseases. In addition to new radiopharmaceuticals testing, often researchers apply well-established probes to animal models, to follow the evolution of the target disease. This reverse translation of standard radiopharmaceuticals to rodent models is complicated by technical shortcomings and by obvious differences between human and rodent cardiac physiology. In addition, radionuclide studies involving small animals are affected by several extrinsic variables, such as the choice of anesthetic. In this paper, we review the major cardiac features that can be studied with classical single-photon and positron-emitting radiopharmaceuticals, namely, cardiac function, perfusion and metabolism, as well as the results and pitfalls of small-animal radionuclide imaging techniques. In addition, we provide a concise guide to the understanding of the most frequently used anesthetics such as ketamine/xylazine, isoflurane, and pentobarbital. We address in particular their mechanisms of action and the potential effects on radionuclide imaging. Indeed, cardiac function, perfusion, and metabolism can all be significantly affected by varying anesthetics and animal handling conditions.

Multi-Scale Imaging of Vascular Pathologies in Cardiovascular Disease

“…Clinically established imaging of vascular pathologies includes structural imaging, such as echocardiography and cardiac MRI ( 27 ), contrast-enhanced ultrasound imaging to measure microvascular blood flow and blood volume ( 23 ), as well as targeted dual-isotope PET viability studies with 13 N-ammonia and 18 F-FDG, to measure myocardial perfusion and viability ( 20 , 24 , 26 , 27 ). Other examples of clinically targeted vascular imaging include imaging of vascular permeability of carotid arteries ( 38 , 110 ), imaging of vessel inflammation by iron oxide nanoparticles ( 59 ), PET/MRI to detect α v β 3 integrin activation and predict outcome in infarct patients ( 89 ) and magnetization transfer MRI for fibrosis evaluation ( 111 ).…”

“…An in vivo mouse study using a clinical SPECT system showed perfect estimation of perfusion defects and non-invasive quantitation of myocardial infarct size (25). Perfusion imaging using either gated blood pool SPECT with 99m Tc-sestamibi or SPECT with labeled erythrocytes using 99m Tc-pertechnetate has low resolution and is mainly used to non-invasively quantify myocardial infarct size (26). Previous studies have used 13 Nammonia for detection of myocardial perfusion, as well as radiolabeled fluorodeoxyglucose (FDG), a glucose tracer, for detection of myocardial glucose metabolism, viability and left ventricular function (26).…”

“…Perfusion imaging using either gated blood pool SPECT with 99m Tc-sestamibi or SPECT with labeled erythrocytes using 99m Tc-pertechnetate has low resolution and is mainly used to non-invasively quantify myocardial infarct size (26). Previous studies have used 13 Nammonia for detection of myocardial perfusion, as well as radiolabeled fluorodeoxyglucose (FDG), a glucose tracer, for detection of myocardial glucose metabolism, viability and left ventricular function (26). These methods are also widely used to quantify myocardial perfusion defects in MI patients (27).…”

Model Corrected Blood Input Function to Compute Cerebral FDG Uptake Rates From Dynamic Total-Body PET Images of Rats in vivo

“…A recent review article ( 16 ) has identified WKY and Sprague–Dawley (SD) rats as commonly used strains in both cardiac PET and SPECT imaging studies. Previous studies have computed and measured cerebral K i in SD rats ( 1 , 11 ).…”

Multiparametric Evaluation of Post-MI Small Animal Models Using Metabolic ([18F]FDG) and Perfusion-Based (SYN1) Heart Viability Tracers

“…The SYN1 tracer has several advantages when compared to other clinically used compounds, including the half-life of the radioisotope ( 18 F) ensuring stable signal and safety to the patients when compared with other isotopes in use (incl. 201 Tl, 82 Rb, 13 N) [8][9][10][11]. SYN1 combines a reasonable half-life of 110 min and the positrons of the lowest energy.…”