Abstract
BackgroundThe “back-translation” of clinically available protocols to measure myocardial perfusion to preclinical imaging in mouse models of human disease is attractive for basic biomedical research. With respect to single-photon emission computed tomography (SPECT) approaches, clinical myocardial perfusion imaging protocols are established with different 99mTc-labeled perfusion tracers; however, studies evaluating and optimizing protocols for these tracers in high-resolution pinhole SPECT in mice are lacking. This study aims at evaluating two clinically available 99mTc-labeled myocardial perfusion tracers (99mTc-sestamibi vs. 99mTc-Tetrofosmin) in mice using four different imaging protocols.MethodsAdult C57BL/6 male mice were injected with 99mTc-sestamibi (MIBI) or 99mTc-Tetrofosmin (TETRO) (4 MBq/g body weight) either intravenously through the tail vein (n = 5) or retroorbitally (n = 5) or intraperitoneally (i.p.) under anesthesia (n = 3) or i.p. in an awake state (n = 3) at rest. Immediately after injection, a multi-frame single-photon emission computed tomography/computed tomography (SPECT/CT) acquisition was initiated with six subsequent time frames of 10 min each. Reconstructed images of the different protocols were assessed and compared by visual analysis by experts and by time-activity-curves generated from regions-of-interest for various organs (normalized uptake values).ResultsVisually assessing overall image quality, the best image quality was found for MIBI for both intravenous injection protocols, whereas TETRO only had comparable image quality after retroorbital injections. These results were confirmed by quantitative analysis where left ventricular (LV) uptake of MIBI after tail vein injections was found significantly higher for all time points accompanied with a significantly slower washout of 16% for MIBI vs. 33% for TETRO (p = 0.009) from 10 to 60 min post injection (PI). Interestingly, LV washout from 10 to 60 min PI was significantly higher for TETRO when applied by tail vein injections when compared to retroorbital injections (22%, p = 0.008). However, liver uptake was significant and comparable for both tracers at all time points. Radioactivity concentration in the lungs was negligible for all time points and both tracers.ConclusionIntravenous MIBI injection (both tail vein and retroorbital) results in the best image quality for assessing myocardial perfusion of the murine heart by SPECT/CT. TETRO has a comparable image quality only for the retroorbital injection route.
Highlights
The “back-translation” of clinically available protocols to measure myocardial perfusion to preclinical imaging in mouse models of human disease is attractive for basic biomedical research
From the three commercially available tracers for singlephoton emission computed tomography (SPECT), 201Thallium, 99mTechnetium-2-methoxy-isobutyl-isonitrile (MIBI) and 99mTechnetium-6,9-bis(2-ethoxyethyl)3,12-dioxa-6,9 diphosphatetradecane (TETRO), the 99mTc-labeled-isonitriles are the ones most frequently employed for myocardial perfusion scintigraphy, mainly due to the convenience of a kit formulation and inhouse labeling, a favorable energy spectrum of 99mTc for myocardial SPECT imaging, and a lower radiation exposure when compared with 201Tl [3,4]
For the intravenous injection routes, mice were injected with 99mTc-sestamibi (MIBI) presented with the best image quality scores for both retroorbital (4.0 ± 0.3) and tail vein (4.0 ± 0.3), whereas TETRO had a slightly lower image quality score of 3.6 ± 0.2 for retroorbital and characteristically lower image quality score of 3.0 ± 0.3 for tail vein injections
Summary
The “back-translation” of clinically available protocols to measure myocardial perfusion to preclinical imaging in mouse models of human disease is attractive for basic biomedical research. With respect to singlephoton emission computed tomography (SPECT) approaches, clinical myocardial perfusion imaging protocols are established with different 99mTc-labeled perfusion tracers; studies evaluating and optimizing protocols for these tracers in high-resolution pinhole SPECT in mice are lacking. This study aims at evaluating two clinically available 99mTc-labeled myocardial perfusion tracers (99mTc-sestamibi vs 99mTc-Tetrofosmin) in mice using four different imaging protocols. Myocardial perfusion scintigraphy is a well-established method in clinical diagnostic algorithms to study patients with coronary heart disease, cardiomyopathies, and other heart diseases and provides at the same time, information on stress and rest perfusion and functional parameters (gated) and prognostic information with both high sensitivity and specificity [1,2]. As shown in various studies the quantitative information provided by these small animal, SPECT systems is sufficiently accurate and reproducible to allow noninvasive assessment of radiotracer biodistribution [7,8]
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