Tenascin-C, an extracellular matrix glycoprotein, appears only in the early stages of embryonic development. It is not normally expressed in the adult heart but does reappear transiently in distinct areas in association with active tissue remodeling. The aim of this study was to explore serial changes in the expression of tenascin-C after myocardial ischemia and reperfusion, using ¹²⁵I-labeled anti–tenascin-C antibody (¹²⁵I-TNC-Ab) in a rat model of acute ischemia and reperfusion. Methods: The left coronary artery was occluded for 20 or 30 min, followed by reperfusion for 1, 3, or 7 d in rats with 20 min of ischemia and for 1, 3, 7, 14, or 28 d in rats with 30 min of ischemia. At the time of the study, ¹²⁵I-TNC-Ab (1.0–2.5 MBq) was injected. Three to 5 h later, to verify the area at risk, ^99mTc-methoxyisobutylisonitrile (100–200 MBq) was injected intravenously just after the left coronary artery reocclusion and the rats were sacrificed 1 min later. Dual-tracer autoradiography was performed to assess ¹²⁵I-TNC-Ab uptake and the area at risk. Results: In rats with 20 min of ischemia, ¹²⁵I-TNC-Ab uptake peaked at 3 d after reperfusion, followed by faint uptake after 7 d (uptake ratios at 1, 3, and 7 d after reperfusion were 1.81 ± 0.53, 2.46 ± 0.79, and 1.23 ± 0.17, respectively [P < 0.05 vs. 3 d]). In rats with 30 min of ischemia, uptake was high at 1 and 3 d after reperfusion (2.99 ± 0.90 and 2.71 ± 0.80, respectively), decreased at 7 and 14 d (1.94 ± 0.23 and 2.06 ± 0.37, respectively), and was weak at 28 d (1.47 ± 0.27, P < 0.005 vs. 1 d, P < 0.05 vs. 3 d). Conclusion: These data indicate that ¹²⁵I-TNC-Ab imaging may be a way to monitor myocardial injury and its repair process after ischemia and reperfusion by visualizing tenascin-C expression.

A relationship between l-[methyl-¹¹C]methionine (¹¹C-methionine) uptake and angiogenesis has been suggested in gliomas. However, methionine uptake in myocardial ischemia and reperfusion has received little attention. We investigated the serial changes and mechanisms of ¹⁴C-methionine uptake in a rat model of myocardial ischemia and reperfusion. Methods: The left coronary artery was occluded for 30 min, followed by reperfusion for 1–28 d. At the time of the study, ¹⁴C-methionine (0.74 MBq) and ²⁰¹Tl (14.8 MBq) were injected intravenously at 20 and 10 min before sacrifice, respectively. One minute before sacrifice, the left coronary artery was reoccluded, and ^99mTc-hexakis-2-methoxyisobutylisonitrile (150–180 MBq) was injected to verify the area at risk. Histologic sections of the heart were immunohistochemically analyzed using anti-CD68, anti–smooth-muscle α-actin (SMA), and antitroponin I and compared with the autoradiography findings. Results: Both ¹⁴C-methionine (uptake ratio, 0.71 ± 0.13) and ²⁰¹Tl uptake were reduced in the area at risk at 1 d after reperfusion. However, 3 d after reperfusion, an increased ¹⁴C-methionine uptake (1.79 ± 0.23) was observed corresponding to the area of still-reduced ²⁰¹Tl uptake, and the ¹⁴C-methionine uptake gradually declined until 28 d. The increased ¹⁴C-methionine uptake area at 3 and 7 d corresponded well to the macrophage infiltrations demonstrated by positive CD68 staining. Anti-SMA staining appeared at 7 d, after which CD68 staining was gradually replaced by the SMA staining, suggesting that methionine uptake in the early phase after ischemia and reperfusion might reflect inflammatory activity. Conclusion: ¹⁴C-methionine accumulated in the infarcted area, and its uptake corresponded closely to macrophage infiltration at 3–7 d after reperfusion. Methionine imaging may be useful for inflammatory imaging early after myocardial infarction.

^99mTc-Annexin-V imaging has been proved to be feasible to detect phosphatidylserine, which externalizes on the outer cell membrane early in the process of apoptosis. To determine whether postconditioning suppresses myocardial cell damage or apoptosis, we evaluated the intensity and distribution of ^99mTc-annexin-V uptake after postconditioning in a rat model of ischemia and reperfusion and compared the effect to that of ischemic preconditioning and pretreatment with caspase inhibitor. Methods: In control rats (n = 13), after thoracotomy the left coronary artery was occluded for 20 min followed by reperfusion for 30 or 90 min and injection of ^99mTc-annexin-V (80–150 MBq). One hour later, to verify the area at risk, ²⁰¹Tl (0.74 MBq) was injected intravenously just beyond the left coronary artery reocclusion, and the rats were sacrificed 1 min later. In the groups of rats with various interventions, postconditioning (n = 11) was performed just after the reperfusion, and preconditioning (n = 11) and caspase inhibitor treatment (n = 11) were performed before ischemia. Dual-tracer autoradiography was performed to assess ^99mTc-annexin-V uptake and area at risk. Results: In all control rats, intense ^99mTc-annexin-V uptake was observed in the area at risk (uptake ratios at 30 or 90 min after reperfusion, 4.15 ± 1.89 and 3.70 ± 1.41, respectively). Postconditioning suppressed ^99mTc-annexin-V uptake (uptake ratios at 30 or 90 min after reperfusion, 2.09 ± 0.56, P < 0.05, and 1.88 ± 0.69, P < 0.05, respectively). Preconditioning also suppressed uptake (uptake ratios at 30 and 90 min after reperfusion, 1.17 ± 0.29, P < 0.005, and 1.33 ± 0.74, P < 0.01, respectively), as did caspase inhibitor (uptake ratios at 30 and 90 min after reperfusion, 2.08 ± 0.50, P < 0.05, and 1.27 ± 0.24, P < 0.005, respectively). In all interventions, the percentage of cells positive on deoxyuride-5′-triphosphate biotin nick end labeling and histologic changes with myocardial cell degeneration and cell infiltrations were suppressed markedly. Conclusion: These data indicate that ^99mTc-annexin-V imaging may be a way to monitor myocardial injury and its response to novel therapeutic interventions including postconditioning, preconditioning, and antiapoptotic therapy.

Detecting culprit coronary arteries in patients with ischemia using only myocardial perfusion single-photon emission computed tomography (SPECT) can be challenging. This study aimed to improve the detection of culprit regions using an artificial neural network (ANN) to analyze hybrid images of coronary computed tomography angiography (CCTA) and myocardial perfusion SPECT. This study enrolled 59 patients with stable coronary artery disease (CAD) who had been assessed by coronary angiography within 60 days of myocardial perfusion SPECT. Two nuclear medicine physicians interpreted the myocardial perfusion SPECT and hybrid images with four grades of confidence, then drew regions on polar maps to identify culprit coronary arteries. The gold standard was determined by the consensus of two other nuclear cardiology specialist based on coronary angiography findings and clinical information. The ability to detect culprit coronary arteries was compared among experienced nuclear cardiologists and the ANN. Receiver operating characteristics (ROC) curves were analyzed and areas under the ROC curves (AUC) were determined. Using hybrid images, observer A detected CAD in the right (RCA), left anterior descending (LAD), and left circumflex (LCX) coronary arteries with 83.6%, 89.3%, and 94.4% accuracy, respectively and observer B did so with 72.9%, 84.2%, and 89.3%, respectively. The ANN was 79.1%, 89.8%, and 89.3% accurate for each coronary artery. Diagnostic accuracy was comparable between the ANN and experienced nuclear medicine physicians. The AUC was significantly improved using hybrid images in the RCA region (observer A: from 0.715 to 0.835, p = 0.0031; observer B: from 0.771 to 0.843, p = 0.042). To detect culprit coronary arteries in perfusion defects of the inferior wall without using hybrid images was problematic because the perfused areas of the LCX and RCA varied among individuals. Hybrid images of CCTA and myocardial perfusion SPECT are useful for detecting culprit coronary arteries. Diagnoses using artificial intelligence are comparable to that by nuclear medicine physicians.