Myocardial Perfusion Imaging Agent < Sup > 99 M < / Sup > Tc - N - Dbodc5 Biological Distribution Characteristics And Diagnosis Of Coronary Heart Disease Research

PART I^99mTc-N-DBODC5, a New Myocardial Perfusion Imaging Agent:Biodistribution Characteristics in RatsObjection: To observed biodistribution characteristics of "mTc-N-DBODC5in rat.Methods: A total of16male Sprague-Dawley rats （200-240g）.①Eight rats wererandomly selected in vivo imaging studies for^99mTc-N-DBODC5and^99mTc-MIBIunder anesthesia; Anterior planar y-camera images were collected at5，15，30，45，60，and120min after injection tracer, with organ uptake quantiifed by region-of-interestanalysis.②After the end of imaging study over7days,16SD rats were randomlyinto four groups,15min group （n=4），30min group （n=4），60min group（n=4） and90min group （n=4）. Rats were euthanized at either15，30，60，or90min after injection^99mTc-N-DBODC5and丫-well counting was performed on excised organ （heart, lungs,liver, kidneys，stomach, mall intestine, muscle） and blood sample.Results: The in vivo biodistribution results show that^99mTc-N-DBODC5signiifcantaccumulation in the myocardium in early at5min and prolonged retention.Myocardial uptake counts of^99mTc-N-DBODC5were slightly lower than the^99mTc-MIBI. The fast liver washout of^99mTc-N-DBODC5was signiifcantly fasterthan the hepatic clearance of^99mTc-MIBI in15min （1.27士O.Olvs.1.83士0.01，/7<0.001）. Lungs uptake of^99mTc-N-DBODC5less than that of^99mTc-MIBI. And therapid lungs clearance of^99mTc-N-DBODC5during the whole experiment. Because ofthe rapid hepatic clearance of^99mTc-N-DBODC5, heart-to-liver ratio of^99mTc-N-DBODC5was signiifcantly higher than^99mTc-MIBI after injection tracer at15min （1.62土0.02vs.0<.73土0.01，/?0.001）. Heart-to-liver ratio of^99mTc-N-DBODC5reached a peak was3.32士0.08and heart-to-liver ratio of "mTc-MIBI was0.95士0.01after injection tracer at60min. The biodistribution in the isolated organs demonstratedthe same trend.Conclusion:^99mTc-N-DBODC5is a promising new myocardial perfusion imagingagent with superior biodistribution properties. The rapid liver clearance of ^99mTc-N-DBODC5may shorten the duration of imaging, and overcome the photonscatter from the liver with high activity which interfered the inferoapical wall onmyocardial images. PART IIBiodistribution and SPECT images of the New Cardiac Tracer^99mTc-N-DBODC5in healthy human volunteersObjection: To evaluate biodistribution behavior and tomography images in healthyhuman volunteers of the new myocardial perfusion tracer bis [（dimethoxypropyl-phosphanyl）ethyl] ethoxyethylamine N，N9-bis（ethoxyethyl）dithiocarbamato nitrido technetium（V）(^99mTc-N-DBODC5).Methods:①Whole-body planar imaging： ifve healthy male volunteers were injectedwith^99mTc-N-DBODC5under both stress and rest conditions. Anterior, posteriorplanar and tomography SPECT images were collected at5，30，60，90，120，150，180and240min after injection, with organ uptake quantiifed by region-of-inetrestanalysis.②SPECT myocardial perfusion imaging： myocardial perfusion imaging（MPI） were performed at the corresponding1，2，and4hour point while whole-bodyplanar imaging were completed at1，2，and4hour.Results:①Afetr injection,^99mTc-N-DBODC5showed signiifcant accumulation inthe myocardium and prolonged retention. Under rest conditions, mean uptake in theheart, lungs, and liver at5min after injection was3.02%士0.03%，2.17%土0.03%and11.470/o士0.02o/o，respectively, of administered activity. Under stress conditions, heartuptake was higher （3.44%土0.06%） at5min. Mean radioactivity in the liver decreasedto5.79%士0.06%and3.28%士0.03%at60and240mm, respectively, after injection.This rapid liver clearance led to favorable heart-to-liver ratios, reaching values of0.81土0.01at rest and1.35士0.01during exercise60min after tracer administration.Radiation dose estimates were comparable to those obtained with other myocardialperfusion cationic compounds.? Tracer evenly was distributed on myocardial ofleft ventricular at1，2，4hour under exercise-rest condition. A clear myocardialperfusion imaging was still seen at4hour.Conclusion:^99mTc-N-DBODC5with high labelled ratio and good biodistributioncharacteristics; and clear myocardial perfusion imaging was seen on healthy volunteers; more importantly, this study provides the basis for the clinical diagnosisof coronary heart disease. PART IIIClinical Study of^99mTc-N-DBODC5as Novel Myocardial Perfusion ImagingAgent for Diagnosis of Coronary Artery DiseaseObjective The aim of this study was to assess the diagnostic value of^99mTc-N-DBODC5for the detection of coronary artery disease （CAD）.Methods①Forty-six patients were numbered according to the order of treatment.Patients were randomly assigned to the experimental group (^99mTc-N-DBODC5) andthe control group (^99mTc-MIBI). If the patient was allotted an odd number, he/shewould ifrst complete exercise-resting^99mTc-N-DBODC5imaging, and then everyother day exercise-resting^99mTc-MIBI imaging. If the patient was assigned an evennumber, he/she would ifrst complete exercise-resting^99mTc-MIBI imaging, and thenevery other day complete exercise-resting^99mTc-N-DBODC5imaging.②Forty-sixpatients with suspected CAD had stress-rest^99mTc-N-DBODC5and technetiumsestamibi (^99mTc-MIBI) myocardial perfusion imaging （MPI） studies with imaging30minutes post-stress and60minutes post-rest injection.? Coronary angiography（CAG） was undertaken1month after of^99mTc-N-DBODC5and^99mTc-MIBI MPI.Results of MPI were compared with coronary angiography in all patients andcorrelation was deifned as the kappa value （k）.④^99mTc-N-DBODC5and^99mTc-MIBIheart-to-organ count ratios were calculated from the anterior projection of eachtomographic acquisition. Regions of interest （ROIs） were drawn around the entire leftventricular myocardium, over the hepatic margin adjacent to the infero-apical wall ofthe left ventricle, excluding the biliary tree, and over the inferior left ventricular walladjacent large intestine activity. The mean counts per pixel in the three ROIs werenormalized to the injected tracer activity after decay correction and to a standardacquisition time of1min.⑤Image quality was scored using a3-point scale system（2=good，1^medium,0^unacceptable）.Results In all the46patients,29had abnormal CAG data and17had normal CAGdata. Overall sensitivity, speciifcity and accuracy of the detection of CAD werehigher with^99mTc-N-DBODC5compared to^99mTc-MIBI. Sensitivity, speciifcity and accuracy were not signiifcantly different but better for^99mTc-N-DBODC5groupwhen compared to^99mTc-MIBI （sensitivity,86-86%; specificity,88-65%; accuracy,87-78%）. Angiography agreement was very good for^99mTc-N-DBODC5（k=0.73）and moderate for^99mTc-MIBI （k=0.52）.Conclusion This study in the clinical trial conifrmed the usefulness of^99mTc-N-DBODC5as a myocardial perfusion imaging agent.