Non-invasive detection and quantification of acute myocardial infarction in rabbits using mono-[123I]iodohypericin microSPECT.

AIMS Mono-[(123)I]iodohypericin ([(123)I]MIH) has been reported to have high avidity for necrosis. In the present study, by using rabbit models of acute myocardial infarction, we explored the suitability of [(123)I]MIH micro single photon emission computed tomography (microSPECT) for non-invasive visualization of myocardial infarcts in comparison with [(13)N]ammonia micro positron emission tomography (microPET) imaging, postmortem histomorphometry, and [(123)I]MIH autoradiography. METHODS AND RESULTS Fourteen rabbits were divided into four groups. The left circumflex coronary artery was permanently occluded in group A (n = 3), reperfused by releasing the ligature after 15 min in group B (n = 3) or 90 min in group C (n = 6), or not occluded in group D (n = 2). Animals received [(13)N]ammonia microPET perfusion imaging 18 h after infarct induction followed by microSPECT imaging at 2-3.5, 9-11, and 22-24 h post injection (p.i.) of [(123)I]MIH. The cardiac images were assembled into polar maps for assessment of tracer uptake. Animals were sacrificed and the excised heart was sliced for autoradiography, triphenyl tetrazolium chloride, and haematoxylin-eosin staining. Using [(123)I]MIH microSPECT, infarcts were well delineated at 9 h p.i. Mean microSPECT infarct size was 38.8 and 32.7% of left ventricular area for groups A and C, respectively, whereas group B showed low uptake of [(123)I]MIH. Highest mean infarct/viable tissue activity ratio of 61/1 was obtained by autoradiography in group C animals at 24 h p.i. CONCLUSION The study indicates the suitability of [(123)I]MIH for in vivo visualization of myocardial infarcts.

[1]  Guy Marchal,et al.  Necrosis Avid Contrast Agents: Functional Similarity Versus Structural Diversity , 2004, Investigative radiology.

[2]  P Suetens,et al.  Model-based quantification of myocardial perfusion images from SPECT. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[3]  D. Meruelo,et al.  The chemical and biological properties of hypericin—a compound with a broad spectrum of biological activities , 1995, Medicinal research reviews.

[4]  H. Strauss,et al.  Comparison of technetium-99m-glucarate and thallium-201 for the identification of acute myocardial infarction in rats. , 1992, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  Michel Defrise,et al.  Interest of the ordered subsets expectation maximization (OS-EM) algorithm in pinhole single-photon emission tomography reconstruction: a phantom study , 2000, European Journal of Nuclear Medicine.

[6]  E. Braunwald,et al.  Myocardial reperfusion: a double-edged sword? , 1985, The Journal of clinical investigation.

[7]  Y. Ni,et al.  Evaluation of tumor affinity of mono-[(123)I]iodohypericin and mono-[(123)I]iodoprotohypericin in a mouse model with a RIF-1 tumor. , 2007, Contrast media & molecular imaging.

[8]  Simon R. Cherry,et al.  Noninvasive Measurement of Myocardial Activity Concentrations and Perfusion Defect Sizes in Rats With a New Small-Animal Positron Emission Tomograph , 2002, Circulation.

[9]  J. Leppo,et al.  A review of cardiac imaging with sestamibi and teboroxime. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[10]  M. Cowley,et al.  Status of the myocardium and infarct-related coronary artery in 19 necropsy patients with acute recanalization using pharmacologic (streptokinase, r-tissue plasminogen activator), mechanical (percutaneous transluminal coronary angioplasty) or combined types of reperfusion therapy. , 1987, Journal of the American College of Cardiology.

[11]  H. Gold,et al.  Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[12]  G Mariani,et al.  Detection of acute myocardial infarction by 99mTc-labeled D-glucaric acid imaging in patients with acute chest pain. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[13]  A. Jaffe,et al.  Quantification of myocardial infarction: a comparison of single photon-emission computed tomography with pyrophosphate to serial plasma MB-creatine kinase measurements. , 1985, Circulation.

[14]  S. Siegel,et al.  Performance evaluation of the microPET focus: a third-generation microPET scanner dedicated to animal imaging. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[15]  Donald W. Wilson,et al.  High-resolution imaging with (99m)Tc-glucarate for assessing myocardial injury in rat heart models exposed to different durations of ischemia with reperfusion. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[16]  M. Welch,et al.  The Dependence of Accumulation of 13NH3 by Myocardium on Metabolic Factors and Its Implications for Quantitative Assessment of Perfusion , 1980, Circulation.

[17]  Guy Marchal,et al.  First preclinical evaluation of mono-[123I]iodohypericin as a necrosis-avid tracer agent , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[18]  G. Bormans,et al.  Preparation, analysis and biodistribution in mice of iodine-123 labelled derivatives of hypericin , 2004 .

[19]  J. Fallon,et al.  Specificity of Localization of Myosin‐specific Antibody Fragments in Experimental Myocardial Infarction: Histologic, Histochemical, Autoradiographic and Scintigraphic Studies , 1979, Circulation.

[20]  G. Takemura,et al.  "Apoptotic" myocytes in infarct area in rabbit hearts may be oncotic myocytes with DNA fragmentation: analysis by immunogold electron microscopy combined with In situ nick end-labeling. , 1998, Circulation.

[21]  J. Nuyts,et al.  Experimental validation of a new quantitative method for the analysis of infarct size by cardiac perfusion tomography (SPECT) , 1993, The International Journal of Cardiac Imaging.

[22]  T. Onodera,et al.  A clinicopathologic study of patients with hemorrhagic myocardial infarction treated with selective coronary thrombolysis with urokinase. , 1986, Circulation.

[23]  R. Gibbons,et al.  Reproducibility of measurements of regional myocardial blood flow in a model of coronary artery disease: Comparison of H215O and 13NH3 PET techniques. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[24]  P. Agostinis,et al.  Hypericin in cancer treatment: more light on the way. , 2002, The international journal of biochemistry & cell biology.

[25]  Robert Woolard,et al.  Missed Diagnoses of Acute Cardiac Ischemia in the Emergency Department , 2000 .

[26]  H. Wellens,et al.  Cardiomyocyte Death Induced by Myocardial Ischemia and Reperfusion: Measurement With Recombinant Human Annexin-V in a Mouse Model , 2000, Circulation.

[27]  R Roberts,et al.  Electrocardiographic and clinical criteria for recognition of acute myocardial infarction based on analysis of 3,697 patients. , 1983, The American journal of cardiology.

[28]  J. Narula,et al.  Very early noninvasive detection of acute experimental nonreperfused myocardial infarction with 99mTc-labeled glucarate. , 1997, Circulation.

[29]  Paul Suetens,et al.  Optimization of geometrical calibration in pinhole SPECT , 2005, IEEE Transactions on Medical Imaging.