Visualization of Dynamic Expression of Myocardial Sigma-1 Receptor After Myocardial Ischemia and Reperfusion Using Radioiodine-Labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) Imaging
Background:This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion.Methods and Results:The left coronary a...
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| Published in | Circulation Journal Vol. 85; no. 11; pp. 2102 - 2108 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Japan
The Japanese Circulation Society
25.10.2021
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 1346-9843 1347-4820 |
| DOI | 10.1253/circj.CJ-21-0320 |
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| Abstract | Background:This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion.Methods and Results:The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5–6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area.Conclusions:The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion. |
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| AbstractList | This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion.Methods and Results:The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with
I-OI5V and
Tc-MIBI was performed to assess the spatiotemporal changes in
I-OI5V uptake (n=5-6). Significant and peaked
I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the
I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with
I-OI5V,
Tc-MIBI, and
TlCl was performed to evaluate
I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The
I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area.
I-OI5V and
Tc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of
I-OI5V in the perfusion defect area.
The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with
I or
I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion. Background:This study chronologically evaluated the expression of the intensity and distribution of the sigma-1 receptor (σ1R) demonstrated by radiolabeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) in a rat model of myocardial ischemia and reperfusion.Methods and Results:The left coronary artery was occluded for 30 min, followed by reperfusion. Dual-tracer autoradiography with 125I-OI5V and 99 mTc-MIBI was performed to assess the spatiotemporal changes in 125I-OI5V uptake (n=5–6). Significant and peaked 125I-OI5V uptake in the ischemic area was observed at 3 days after reperfusion, and the 125I-OI5V uptake ratio of ischemic area to normally perfused left ventricular area decreased gradually from 3 to 28 days (mean value±SD; 0.90±0.12 at 1 day, 1.89±0.19 at 3 days, 1.52±0.17 at 7 days, 1.34±0.13 at 14 days, and 1.16±0.14 at 28 days, respectively). Triple-tracer autoradiography with 125I-OI5V, 99 mTc-MIBI, and 201TlCl was performed to evaluate 125I-OI5V uptake in the ischemic area in relation to the residual perfusion at 7 days (n=4). The 125I-OI5V uptake ratio of the non-salvaged area was higher compared to that of the salvaged area in the ischemic area. 123I-OI5V and 99 mTc-MIBI SPECT/CT was performed 3 days after reperfusion (n=3), and the in vivo images showed clear uptake of 123I-OI5V in the perfusion defect area.Conclusions:The present study confirmed the spatiotemporal expression pattern of σ1R expression. Non-invasive σ1R imaging with 123I or 125I-OI5V was feasible to monitor the expression of σ1R after myocardial ischemia and reperfusion. |
| ArticleNumber | CJ-21-0320 |
| Author | Shiba, Kazuhiro Kinuya, Seigo Ogawa, Kazuma Inaki, Anri Kozaka, Takashi Akatani, Norihito Wakabayashi, Hiroshi Hiromasa, Tomo Mori, Hiroshi Taki, Junichi |
| Author_xml | – sequence: 1 fullname: Kozaka, Takashi organization: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University – sequence: 1 fullname: Ogawa, Kazuma organization: Institute for Frontier Science Initiative, Kanazawa University – sequence: 1 fullname: Taki, Junichi organization: Department of Nuclear Medicine, Kanazawa University Hospital – sequence: 1 fullname: Akatani, Norihito organization: Department of Nuclear Medicine, Kanazawa University Hospital – sequence: 1 fullname: Hiromasa, Tomo organization: Department of Nuclear Medicine, Kanazawa University Hospital – sequence: 1 fullname: Wakabayashi, Hiroshi organization: Department of Nuclear Medicine, Kanazawa University Hospital – sequence: 1 fullname: Inaki, Anri organization: Department of Nuclear Medicine, Kanazawa University Hospital – sequence: 1 fullname: Shiba, Kazuhiro organization: Division of Tracer Kinetics, Advanced Science Research Center, Kanazawa University – sequence: 1 fullname: Mori, Hiroshi organization: Department of Nuclear Medicine, Kanazawa University Hospital – sequence: 1 fullname: Kinuya, Seigo organization: Department of Nuclear Medicine, Kanazawa University Hospital |
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| Cites_doi | 10.1073/pnas.93.15.8072 10.1088/0031-9155/55/7/015 10.1007/s12149-015-0966-6 10.1517/14728222.2010.509348 10.1162/153535003322556877 10.1093/cvr/cvu049 10.1111/bph.13888 10.33549/physiolres.934052 10.1016/0922-4106(94)90115-5 10.1152/ajpheart.00198.2010 10.1016/0014-2999(95)00424-J 10.3389/fphys.2018.00755 10.2174/1570159X15666170529104323 10.1016/j.tips.2016.01.003 10.1038/aps.2015.145 10.1016/0165-6147(92)90030-A 10.1161/JAHA.118.009775 10.1007/s12149-020-01552-w 10.1161/CIRCIMAGING.110.961854 10.1016/j.ijcha.2019.100449 10.1093/brain/awq367 |
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| Keywords | Myocardial ischemia Memory imaging Sigma-1 receptor OI5V |
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| References | 8. Vilner BJ, John CS, Bowen WD. Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. Cancer Res 1995; 55: 408–413. 19. Zhou H, Wang S, Hu S, Chen Y, Ren J. ER-Mitochondria microdomains in cardiac ischemia-reperfusion injury: A fresh perspective. Front Physiol 2018; 9: 755. 24. Bhuiyan MS, Tagashira H, Shioda N, Fukunaga K. Targeting sigma-1 receptor with fluvoxamine ameliorates pressure-overload-induced hypertrophy and dysfunctions. Expert Opin Ther Targets 2010; 14: 1009–1022. 16. Ela C, Barg J, Vogel Z, Hasin Y, Eilam Y. Sigma receptor ligands modulate contractility, Ca++ influx and beating rate in cultured cardiac myocytes. J Pharmacol Exp Ther 1994; 269: 1300–1309. 23. Liu MQ, Chen Z, Chen LX. Endoplasmic reticulum stress: A novel mechanism and therapeutic target for cardiovascular diseases. Acta Pharmacol Sin 2016; 37: 425–443. 4. Hanner M, Moebius FF, Flandorfer A, Knaus HG, Striessnig J, Kempner E, et al. Purification, molecular cloning, and expression of the mammalian sigma1-binding site. Proc Natl Acad Sci USA 1996; 93: 8072–8077. 17. Novakova M, Ela C, Barg J, Vogel Z, Hasin Y, Eilam Y. Inotropic action of sigma receptor ligands in isolated cardiac myocytes from adult rats. Eur J Pharmacol 1995; 286: 19–30. 3. Hellewell SB, Bruce A, Feinstein G, Orringer J, Williams W, Bowen WD. Rat liver and kidney contain high densities of sigma 1 and sigma 2 receptors: Characterization by ligand binding and photoaffinity labeling. Eur J Pharmacol 1994; 268: 9–18. 7. Penke B, Fulop L, Szucs M, Frecska E. The role of Sigma-1 receptor, an intracellular chaperone in neurodegenerative diseases. Curr Neuropharmacol 2018; 16: 97–116. 2. Quirion R, Bowen WD, Itzhak Y, Junien JL, Musacchio JM, Rothman RB, et al. A proposal for the classification of sigma binding sites. Trends Pharmacol Sci 1992; 13: 85–86. 14. Miwa K, Inubushi M, Takeuchi Y, Katafuchi T, Koizumi M, Saga T, et al. Performance characteristics of a novel clustered multi-pinhole technology for simultaneous high-resolution SPECT/PET. Ann Nucl Med 2015; 29: 460–466. 6. Su TP, Su TC, Nakamura Y, Tsai SY. The Sigma-1 receptor as a pluripotent modulator in living systems. Trends Pharmacol Sci 2016; 37: 262–278. 5. Stracina T, Novakova M. Cardiac sigma receptors: An update. Physiol Res 2018; 67: S561–S576. 12. Sahul ZH, Mukherjee R, Song J, McAteer J, Stroud RE, Dione DP, et al. Targeted imaging of the spatial and temporal variation of matrix metalloproteinase activity in a porcine model of postinfarct remodeling: Relationship to myocardial dysfunction. Circ Cardiovasc Imaging 2011; 4: 381–391. 20. Ruscher K, Shamloo M, Rickhag M, Ladunga I, Soriano L, Gisselsson L, et al. The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke. Brain 2011; 134: 732–746. 1. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 1976; 197: 517–532. 18. Lewis R, Li J, McCormick PJ, Huang CLH, Jeevaratnam K. Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies?: A systematic review. Int J Cardiol Heart Vasc 2019; 26: 100449. 21. Tarone G, Brancaccio M. Keep your heart in shape: Molecular chaperone networks for treating heart disease. Cardiovasc Res 2014; 102: 346–361. 22. Wang S, Binder P, Fang Q, Wang Z, Xiao W, Liu W, et al. Endoplasmic reticulum stress in the heart: Insights into mechanisms and drug targets. Br J Pharmacol 2018; 175: 1293–1304. 10. Tagashira H, Bhuiyan S, Shioda N, Hasegawa H, Kanai H, Fukunaga K. Sigma1-receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice. Am J Physiol Heart Circ Physiol 2010; 299: H1535–H1545. 11. Shigeno T, Kozaka T, Kitamura Y, Ogawa K, Taki J, Kinuya S, et al. In vitro and in vivo evaluation of [(125/123)I]-2-[4-(2-iodophenyl)piperidino]cyclopentanol([(125/123)I]-OI5V) as a potential sigma-1 receptor ligand for SPECT. Ann Nucl Med 2021; 35: 167–175. 13. Branderhorst W, Vastenhouw B, Beekman FJ. Pixel-based subsets for rapid multi-pinhole SPECT reconstruction. Phys Med Biol 2010; 55: 2023–2034. 15. Loening AM, Gambhir SS. AMIDE: A free software tool for multimodality medical image analysis. Mol Imaging 2003; 2: 131–137. 9. Abdullah CS, Alam S, Aishwarya R, Miriyala S, Panchatcharam M, Bhuiyan MAN, et al. Cardiac dysfunction in the Sigma 1 receptor knockout mouse associated with impaired mitochondrial dynamics and bioenergetics. J Am Heart Assoc 2018; 7: e009775. 11 22 12 23 13 24 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 10 21 34456203 - Circ J. 2021 Oct 25;85(11):2109-2110 |
| References_xml | – reference: 24. Bhuiyan MS, Tagashira H, Shioda N, Fukunaga K. Targeting sigma-1 receptor with fluvoxamine ameliorates pressure-overload-induced hypertrophy and dysfunctions. Expert Opin Ther Targets 2010; 14: 1009–1022. – reference: 19. Zhou H, Wang S, Hu S, Chen Y, Ren J. ER-Mitochondria microdomains in cardiac ischemia-reperfusion injury: A fresh perspective. Front Physiol 2018; 9: 755. – reference: 6. Su TP, Su TC, Nakamura Y, Tsai SY. The Sigma-1 receptor as a pluripotent modulator in living systems. Trends Pharmacol Sci 2016; 37: 262–278. – reference: 23. Liu MQ, Chen Z, Chen LX. Endoplasmic reticulum stress: A novel mechanism and therapeutic target for cardiovascular diseases. Acta Pharmacol Sin 2016; 37: 425–443. – reference: 13. Branderhorst W, Vastenhouw B, Beekman FJ. Pixel-based subsets for rapid multi-pinhole SPECT reconstruction. Phys Med Biol 2010; 55: 2023–2034. – reference: 1. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE. The effects of morphine- and nalorphine- like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 1976; 197: 517–532. – reference: 11. Shigeno T, Kozaka T, Kitamura Y, Ogawa K, Taki J, Kinuya S, et al. In vitro and in vivo evaluation of [(125/123)I]-2-[4-(2-iodophenyl)piperidino]cyclopentanol([(125/123)I]-OI5V) as a potential sigma-1 receptor ligand for SPECT. Ann Nucl Med 2021; 35: 167–175. – reference: 8. Vilner BJ, John CS, Bowen WD. Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines. Cancer Res 1995; 55: 408–413. – reference: 4. Hanner M, Moebius FF, Flandorfer A, Knaus HG, Striessnig J, Kempner E, et al. Purification, molecular cloning, and expression of the mammalian sigma1-binding site. Proc Natl Acad Sci USA 1996; 93: 8072–8077. – reference: 2. Quirion R, Bowen WD, Itzhak Y, Junien JL, Musacchio JM, Rothman RB, et al. A proposal for the classification of sigma binding sites. Trends Pharmacol Sci 1992; 13: 85–86. – reference: 15. Loening AM, Gambhir SS. AMIDE: A free software tool for multimodality medical image analysis. Mol Imaging 2003; 2: 131–137. – reference: 17. Novakova M, Ela C, Barg J, Vogel Z, Hasin Y, Eilam Y. Inotropic action of sigma receptor ligands in isolated cardiac myocytes from adult rats. Eur J Pharmacol 1995; 286: 19–30. – reference: 10. Tagashira H, Bhuiyan S, Shioda N, Hasegawa H, Kanai H, Fukunaga K. Sigma1-receptor stimulation with fluvoxamine ameliorates transverse aortic constriction-induced myocardial hypertrophy and dysfunction in mice. Am J Physiol Heart Circ Physiol 2010; 299: H1535–H1545. – reference: 3. Hellewell SB, Bruce A, Feinstein G, Orringer J, Williams W, Bowen WD. Rat liver and kidney contain high densities of sigma 1 and sigma 2 receptors: Characterization by ligand binding and photoaffinity labeling. Eur J Pharmacol 1994; 268: 9–18. – reference: 9. Abdullah CS, Alam S, Aishwarya R, Miriyala S, Panchatcharam M, Bhuiyan MAN, et al. Cardiac dysfunction in the Sigma 1 receptor knockout mouse associated with impaired mitochondrial dynamics and bioenergetics. J Am Heart Assoc 2018; 7: e009775. – reference: 18. Lewis R, Li J, McCormick PJ, Huang CLH, Jeevaratnam K. Is the sigma-1 receptor a potential pharmacological target for cardiac pathologies?: A systematic review. Int J Cardiol Heart Vasc 2019; 26: 100449. – reference: 21. Tarone G, Brancaccio M. Keep your heart in shape: Molecular chaperone networks for treating heart disease. Cardiovasc Res 2014; 102: 346–361. – reference: 7. Penke B, Fulop L, Szucs M, Frecska E. The role of Sigma-1 receptor, an intracellular chaperone in neurodegenerative diseases. Curr Neuropharmacol 2018; 16: 97–116. – reference: 20. Ruscher K, Shamloo M, Rickhag M, Ladunga I, Soriano L, Gisselsson L, et al. The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke. Brain 2011; 134: 732–746. – reference: 5. Stracina T, Novakova M. Cardiac sigma receptors: An update. Physiol Res 2018; 67: S561–S576. – reference: 14. Miwa K, Inubushi M, Takeuchi Y, Katafuchi T, Koizumi M, Saga T, et al. Performance characteristics of a novel clustered multi-pinhole technology for simultaneous high-resolution SPECT/PET. Ann Nucl Med 2015; 29: 460–466. – reference: 12. Sahul ZH, Mukherjee R, Song J, McAteer J, Stroud RE, Dione DP, et al. Targeted imaging of the spatial and temporal variation of matrix metalloproteinase activity in a porcine model of postinfarct remodeling: Relationship to myocardial dysfunction. Circ Cardiovasc Imaging 2011; 4: 381–391. – reference: 16. Ela C, Barg J, Vogel Z, Hasin Y, Eilam Y. Sigma receptor ligands modulate contractility, Ca++ influx and beating rate in cultured cardiac myocytes. J Pharmacol Exp Ther 1994; 269: 1300–1309. – reference: 22. Wang S, Binder P, Fang Q, Wang Z, Xiao W, Liu W, et al. Endoplasmic reticulum stress in the heart: Insights into mechanisms and drug targets. Br J Pharmacol 2018; 175: 1293–1304. – ident: 1 – ident: 4 doi: 10.1073/pnas.93.15.8072 – ident: 13 doi: 10.1088/0031-9155/55/7/015 – ident: 14 doi: 10.1007/s12149-015-0966-6 – ident: 24 doi: 10.1517/14728222.2010.509348 – ident: 15 doi: 10.1162/153535003322556877 – ident: 21 doi: 10.1093/cvr/cvu049 – ident: 16 – ident: 22 doi: 10.1111/bph.13888 – ident: 5 doi: 10.33549/physiolres.934052 – ident: 3 doi: 10.1016/0922-4106(94)90115-5 – ident: 10 doi: 10.1152/ajpheart.00198.2010 – ident: 17 doi: 10.1016/0014-2999(95)00424-J – ident: 19 doi: 10.3389/fphys.2018.00755 – ident: 7 doi: 10.2174/1570159X15666170529104323 – ident: 6 doi: 10.1016/j.tips.2016.01.003 – ident: 8 – ident: 23 doi: 10.1038/aps.2015.145 – ident: 2 doi: 10.1016/0165-6147(92)90030-A – ident: 9 doi: 10.1161/JAHA.118.009775 – ident: 11 doi: 10.1007/s12149-020-01552-w – ident: 12 doi: 10.1161/CIRCIMAGING.110.961854 – ident: 18 doi: 10.1016/j.ijcha.2019.100449 – ident: 20 doi: 10.1093/brain/awq367 – reference: 34456203 - Circ J. 2021 Oct 25;85(11):2109-2110 |
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| SubjectTerms | Animals Coronary Artery Disease Cyclopentanes Humans Iodine Radioisotopes Memory imaging Myocardial ischemia Myocardial Ischemia - diagnostic imaging Myocardial Reperfusion Myocardium OI5V Radiopharmaceuticals Rats Receptors, sigma Reperfusion Sigma-1 Receptor Technetium Tc 99m Sestamibi |
| Title | Visualization of Dynamic Expression of Myocardial Sigma-1 Receptor After Myocardial Ischemia and Reperfusion Using Radioiodine-Labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) Imaging |
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