Skip to main content

Advertisement

SpringerLink
Log in

Phosphatidylethanolamine targeting for cell death imaging in early treatment response evaluation and disease diagnosis

  • Review
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Phosphatidylethanolamine (PE) is one of the most abundant phospholipids in mammalian plasma membranes. In healthy cells, PE resides predominantly in the inner leaflet of the cell membrane. In dead or dying cells on the other hand, PE is externalized to the outer leaflet of the plasma membrane. The exposure of PE on the cell surface has therefore become an attractive target for the molecular imaging of cell death using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). This has motivated the development of PE-specific probes to measure cell death in vitro and non-invasively in vivo. In this review, we highlight the biological roles of PE on cell membranes, and PE exposure as a biomarker of cell death in disease processes, along with the use of PE-binding molecular probes to target PE for the characterization of cell death on a cellular and tissue level. We specifically emphasize the preclinical applications of radiolabeled duramycin for the non-invasive imaging of cell death in animal models of disease and in tumors after therapy. In addition, we discuss the clinical relevance, limitations and future perspectives of this imaging approach of cell death.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Adapted from reference [44]

Fig. 5
Fig. 6

Adapted from reference [71]

Fig. 7

Adapted from reference [82]

Fig. 8

Adapted from reference [89]

Fig. 9

Adapted from reference [91]. (Color figure online)

Similar content being viewed by others

References

  1. van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9(2):112–124. doi:10.1038/nrm2330

    Article  PubMed  PubMed Central  Google Scholar 

  2. Fadeel B, Xue D (2009) The ins and outs of phospholipid asymmetry in the plasma membrane: roles in health and disease. Crit Rev Biochem Mol Biol 44(5):264–277. doi:10.1080/10409230903193307

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Orr JW, Newton AC (1992) Interaction of protein kinase C with phosphatidylserine. 2. Specificity and regulation. BioChemistry 31(19):4667–4673

    Article  CAS  PubMed  Google Scholar 

  4. Emoto K, Toyama-Sorimachi N, Karasuyama H, Inoue K, Umeda M (1997) Exposure of phosphatidylethanolamine on the surface of apoptotic cells. Exp Cell Res 232(2):430–434. doi:10.1006/excr.1997.3521

    Article  CAS  PubMed  Google Scholar 

  5. Zhao M, Li Z, Bugenhagen S (2008) 99mTc-labeled duramycin as a novel phosphatidylethanolamine-binding molecular probe. J Nucl Med 49(8):1345–1352. doi:10.2967/jnumed.107.048603

    Article  CAS  PubMed  Google Scholar 

  6. Blankenberg FG, Katsikis PD, Tait JF, Davis RE, Naumovski L, Ohtsuki K, Kopiwoda S, Abrams MJ, Darkes M, Robbins RC, Maecker HT, Strauss HW (1998) In vivo detection and imaging of phosphatidylserine expression during programmed cell death. Proc Natl Acad Sci USA 95(11):6349–6354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Benali K, Louedec L, Azzouna RB, Merceron O, Nassar P, Al Shoukr F, Petiet A, Barbato D, Michel JB, Sarda-Mantel L, Le Guludec D, Rouzet F (2014) Preclinical validation of 99mTc-annexin A5-128 in experimental autoimmune myocarditis and infective endocarditis: comparison with 99mTc-HYNIC-annexin A5. Mol Imaging. doi:10.2310/7290.2014.00049

    PubMed  Google Scholar 

  8. Maffey KG, Keil LB, DeBari VA (2001) The influence of lipid composition and divalent cations on annexin V binding to phospholipid mixtures. Ann Clin Lab Sci 31(1):85–90

    CAS  PubMed  Google Scholar 

  9. Belhocine TZ, Blankenberg FG, Kartachova MS, Stitt LW, Vanderheyden JL, Hoebers FJ, Van de Wiele C (2015) 99mTc-Annexin A5 quantification of apoptotic tumor response: a systematic review and meta-analysis of clinical imaging trials. Eur J Nucl Med Mol Imaging 42(13):2083–2097. doi:10.1007/s00259-015-3152-0

    Article  CAS  PubMed  Google Scholar 

  10. Boersma HH, Kietselaer BL, Stolk LM, Bennaghmouch A, Hofstra L, Narula J, Heidendal GA, Reutelingsperger CP (2005) Past, present, and future of annexin A5: from protein discovery to clinical applications. J Nucl Med 46(12):2035–2050

    CAS  PubMed  Google Scholar 

  11. Schutters K, Reutelingsperger C (2010) Phosphatidylserine targeting for diagnosis and treatment of human diseases. Apoptosis 15(9):1072–1082. doi:10.1007/s10495-010-0503-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) The lipid bilayer. In: Molecular biology of the cell, 4th edn. Garland Science, New York. https://www.ncbi.nlm.nih.gov/books/NBK26871/

  13. Hullin-Matsuda F, Makino A, Murate M, Kobayashi T (2016) Probing phosphoethanolamine-containing lipids in membranes with duramycin/cinnamycin and aegerolysin proteins. Biochimie 130:81–90. doi:10.1016/j.biochi.2016.09.020

    Article  CAS  PubMed  Google Scholar 

  14. Post JA, Verkleij AJ, Langer GA (1995) Organization and function of sarcolemmal phospholipids in control and ischemic/reperfused cardiomyocytes. J Mol Cell Cardiol 27(2):749–760

    Article  CAS  PubMed  Google Scholar 

  15. Emoto K, Kobayashi T, Yamaji A, Aizawa H, Yahara I, Inoue K, Umeda M (1996) Redistribution of phosphatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis. Proc Natl Acad Sci USA 93(23):12867–12872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sprong H, van der Sluijs P, van Meer G (2001) How proteins move lipids and lipids move proteins. Nat Rev Mol Cell Biol 2(7):504–513

    Article  CAS  PubMed  Google Scholar 

  17. van der Wel PC, Pott T, Morein S, Greathouse DV, Koeppe RE 2nd, Killian JA (2000) Tryptophan-anchored transmembrane peptides promote formation of nonlamellar phases in phosphatidylethanolamine model membranes in a mismatch-dependent manner. BioChemistry 39(11):3124–3133

    Article  PubMed  Google Scholar 

  18. Vance JE, Tasseva G (2013) Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells. Biochim Biophys Acta 1831(3):543–554. doi:10.1016/j.bbalip.2012.08.016

    Article  CAS  PubMed  Google Scholar 

  19. Vance JE (2008) Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids. J Lipid Res 49(7):1377–1387. doi:10.1194/jlr.R700020-JLR200

    Article  CAS  PubMed  Google Scholar 

  20. Jin XH, Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N (2007) Discovery and characterization of a Ca2+-independent phosphatidylethanolamine N-acyltransferase generating the anandamide precursor and its congeners. J Biol Chem 282(6):3614–3623. doi:10.1074/jbc.M606369200

    Article  CAS  PubMed  Google Scholar 

  21. Gao X, van der Veen JN, Vance JE, Thiesen A, Vance DE, Jacobs RL (2015) Lack of phosphatidylethanolamine N-methyltransferase alters hepatic phospholipid composition and induces endoplasmic reticulum stress. Biochim Biophys Acta 1852(12):2689–2699. doi:10.1016/j.bbadis.2015.09.006

    Article  CAS  PubMed  Google Scholar 

  22. Steenbergen R, Nanowski TS, Beigneux A, Kulinski A, Young SG, Vance JE (2005) Disruption of the phosphatidylserine decarboxylase gene in mice causes embryonic lethality and mitochondrial defects. J Biol Chem 280(48):40032–40040. doi:10.1074/jbc.M506510200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Leventis PA, Grinstein S (2010) The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys 39:407–427. doi:10.1146/annurev.biophys.093008.131234

    Article  CAS  PubMed  Google Scholar 

  24. Bratton DL, Fadok VA, Richter DA, Kailey JM, Guthrie LA, Henson PM (1997) Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated nonspecific flip-flop and is enhanced by loss of the aminophospholipid translocase. J Biol Chem 272(42):26159–26165

    Article  CAS  PubMed  Google Scholar 

  25. Verhoven B, Schlegel RA, Williamson P (1995) Mechanisms of phosphatidylserine exposure, a phagocyte recognition signal, on apoptotic T lymphocytes. J Exp Med 182(5):1597–1601

    Article  CAS  PubMed  Google Scholar 

  26. Williamson P, Schlegel RA (2002) Transbilayer phospholipid movement and the clearance of apoptotic cells. Biochim Biophys Acta 1585(2–3):53–63

    Article  CAS  PubMed  Google Scholar 

  27. Aoki Y, Uenaka T, Aoki J, Umeda M, Inoue K (1994) A novel peptide probe for studying the transbilayer movement of phosphatidylethanolamine. J Biochem 116(2):291–297

    Article  CAS  PubMed  Google Scholar 

  28. Suzuki J, Umeda M, Sims PJ, Nagata S (2010) Calcium-dependent phospholipid scrambling by TMEM16F. Nature 468(7325):834–838. doi:10.1038/nature09583

    Article  CAS  PubMed  Google Scholar 

  29. Suzuki J, Denning DP, Imanishi E, Horvitz HR, Nagata S (2013) Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science 341(6144):403–406. doi:10.1126/science.1236758

    Article  CAS  PubMed  Google Scholar 

  30. Barnett Foster D, Abul-Milh M, Huesca M, Lingwood CA (2000) Enterohemorrhagic Escherichia coli induces apoptosis which augments bacterial binding and phosphatidylethanolamine exposure on the plasma membrane outer leaflet. Infect Immun 68(6):3108–3115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Marconescu A, Thorpe PE (2008) Coincident exposure of phosphatidylethanolamine and anionic phospholipids on the surface of irradiated cells. Biochim Biophys Acta 1778(10):2217–2224. doi:10.1016/j.bbamem.2008.05.006

    Article  CAS  PubMed  Google Scholar 

  32. Fadeel B, Gleiss B, Hogstrand K, Chandra J, Wiedmer T, Sims PJ, Henter JI, Orrenius S, Samali A (1999) Phosphatidylserine exposure during apoptosis is a cell-type-specific event and does not correlate with plasma membrane phospholipid scramblase expression. Biochem Biophys Res Commun 266(2):504–511. doi:10.1006/bbrc.1999.1820

    Article  CAS  PubMed  Google Scholar 

  33. Vallabhapurapu SD, Blanco VM, Sulaiman MK, Vallabhapurapu SL, Chu Z, Franco RS, Qi X (2015) Variation in human cancer cell external phosphatidylserine is regulated by flippase activity and intracellular calcium. Oncotarget 6(33):34375–34388. doi:10.18632/oncotarget.6045

    PubMed  PubMed Central  Google Scholar 

  34. Wesselborg S, Engels IH, Rossmann E, Los M, Schulze-Osthoff K (1999) Anticancer drugs induce caspase-8/FLICE activation and apoptosis in the absence of CD95 receptor/ligand interaction. Blood 93(9):3053–3063

    CAS  PubMed  Google Scholar 

  35. Ferraro-Peyret C, Quemeneur L, Flacher M, Revillard JP, Genestier L (2002) Caspase-independent phosphatidylserine exposure during apoptosis of primary T lymphocytes. J Immunol 169(9):4805–4810

    Article  PubMed  Google Scholar 

  36. Bezabeh T, Mowat MR, Jarolim L, Greenberg AH, Smith IC (2001) Detection of drug-induced apoptosis and necrosis in human cervical carcinoma cells using 1 H NMR spectroscopy. Cell Death Differ 8(3):219–224. doi:10.1038/sj.cdd.4400802

    Article  CAS  PubMed  Google Scholar 

  37. Hamon Y, Broccardo C, Chambenoit O, Luciani MF, Toti F, Chaslin S, Freyssinet JM, Devaux PF, McNeish J, Marguet D, Chimini G (2000) ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine. Nat Cell Biol 2(7):399–406. doi:10.1038/35017029

    Article  CAS  PubMed  Google Scholar 

  38. Umeda M, Emoto K (1999) Membrane phospholipid dynamics during cytokinesis: regulation of actin filament assembly by redistribution of membrane surface phospholipid. Chem Phys Lipids 101(1):81–91

    Article  CAS  PubMed  Google Scholar 

  39. Ran S, Thorpe PE (2002) Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy. Int J Radiat Oncol Biol Phys 54(5):1479–1484

    Article  CAS  PubMed  Google Scholar 

  40. Stafford JH, Thorpe PE (2011) Increased exposure of phosphatidylethanolamine on the surface of tumor vascular endothelium. Neoplasia 13(4):299–308

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Niu G, Chen X (2010) Apoptosis imaging: beyond annexin V. J Nucl Med 51(11):1659–1662. doi:10.2967/jnumed.110.078584

    Article  CAS  PubMed  Google Scholar 

  42. Guder A, Wiedemann I, Sahl HG (2000) Posttranslationally modified bacteriocins: the lantibiotics. Biopolymers 55(1):62–73. doi:10.1002/1097-0282(2000)55:1<62::AID-BIP60>3.0.CO;2-Y

    Article  CAS  PubMed  Google Scholar 

  43. Kessler H, Steuernagel S, Will M, Jung G, Kellner R, Gillessen D, Kamiyama T (1988) The structure of the polycyclic nonadecapeptide Ro 09-0198. Helv Chim Acta 71(8):1924–1929. doi:10.1002/hlca.19880710811

    Article  CAS  Google Scholar 

  44. Zhao M (2011) Lantibiotics as probes for phosphatidylethanolamine. Amino Acids 41(5):1071–1079. doi:10.1007/s00726-009-0386-9

    Article  CAS  PubMed  Google Scholar 

  45. Machaidze G, Ziegler A, Seelig J (2002) Specific binding of Ro 09-0198 (cinnamycin) to phosphatidylethanolamine: a thermodynamic analysis. BioChemistry 41(6):1965–1971

    Article  CAS  PubMed  Google Scholar 

  46. Machaidze G, Seelig J (2003) Specific binding of cinnamycin (Ro 09-0198) to phosphatidylethanolamine. Comparison between micellar and membrane environments. BioChemistry 42(43):12570–12576. doi:10.1021/bi035225b

    Article  CAS  PubMed  Google Scholar 

  47. Iwamoto K, Hayakawa T, Murate M, Makino A, Ito K, Fujisawa T, Kobayashi T (2007) Curvature-dependent recognition of ethanolamine phospholipids by duramycin and cinnamycin. Biophys J 93(5):1608–1619. doi:10.1529/biophysj.106.101584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Choung SY, Kobayashi T, Takemoto K, Ishitsuka H, Inoue K (1988) Interaction of a cyclic peptide, Ro09-0198, with phosphatidylethanolamine in liposomal membranes. Biochim Biophys Acta 940(2):180–187

    Article  CAS  PubMed  Google Scholar 

  49. Cotter PD, Hill C, Ross RP (2005) Bacteriocins: developing innate immunity for food. Nat Rev Microbiol 3(10):777–788. doi:10.1038/nrmicro1273

    Article  CAS  PubMed  Google Scholar 

  50. Makino A, Baba T, Fujimoto K, Iwamoto K, Yano Y, Terada N, Ohno S, Sato SB, Ohta A, Umeda M, Matsuzaki K, Kobayashi T (2003) Cinnamycin (Ro 09-0198) promotes cell binding and toxicity by inducing transbilayer lipid movement. J Biol Chem 278(5):3204–3209. doi:10.1074/jbc.M210347200

    Article  CAS  PubMed  Google Scholar 

  51. Rzeznicka II, Sovago M, Backus EH, Bonn M, Yamada T, Kobayashi T, Kawai M (2010) Duramycin-induced destabilization of a phosphatidylethanolamine monolayer at the air-water interface observed by vibrational sum-frequency generation spectroscopy. Langmuir 26(20):16055–16062. doi:10.1021/la1028965

    Article  CAS  PubMed  Google Scholar 

  52. Wakamatsu K, Choung SY, Kobayashi T, Inoue K, Higashijima T, Miyazawa T (1990) Complex formation of peptide antibiotic Ro09-0198 with lysophosphatidylethanolamine: 1 H NMR analyses in dimethyl sulfoxide solution. BioChemistry 29(1):113–118

    Article  CAS  PubMed  Google Scholar 

  53. Hou S, Johnson SE, Zhao M (2015) A one-step staining probe for phosphatidylethanolamine. ChemBioChem. doi:10.1002/cbic.201500127

    PubMed  Google Scholar 

  54. Broughton LJ, Giuntini F, Savoie H, Bryden F, Boyle RW, Maraveyas A, Madden LA (2016) Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy. J Photochem Photobiol B 163:374–384. doi:10.1016/j.jphotobiol.2016.09.001

    Article  CAS  PubMed  Google Scholar 

  55. Li Z, Wells CW, Esmon CT, Zhao M (2009) Phosphatidylethanolamine at the endothelial surface of aortic flow dividers. J Thromb Haemost 7(1):227–229. doi:10.1111/j.1538-7836.2008.03193.x

    Article  CAS  PubMed  Google Scholar 

  56. Zhao M, Li Z (2012) A single-step kit formulation for the 99mTc-labeling of HYNIC-duramycin. Nucl Med Biol 39(7):1006–1011. doi:10.1016/j.nucmedbio.2012.03.006

    Article  CAS  PubMed  Google Scholar 

  57. Wang L, Wang F, Fang W, Johnson SE, Audi S, Zimmer M, Holly TA, Lee DC, Zhu B, Zhu H, Zhao M (2015) The feasibility of imaging myocardial ischemic/reperfusion injury using 99mTc-labeled duramycin in a porcine model. Nucl Med Biol 42(2):198–204. doi:10.1016/j.nucmedbio.2014.09.002

    Article  PubMed  Google Scholar 

  58. Elvas F, Vangestel C, Rapic S, Verhaeghe J, Gray B, Pak K, Stroobants S, Staelens S, Wyffels L (2015) Characterization of [99mTc]duramycin as a SPECT imaging agent for early assessment of tumor apoptosis. Mol Imaging Biol 17(6):838–847. doi:10.1007/s11307-015-0852-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Yao S, Hu K, Tang G, Liang X, Du K, Nie D, Jiang S, Zang L (2014) Positron emission tomography imaging of cell death with [(18)F]FPDuramycin. Apoptosis 19(5):841–850. doi:10.1007/s10495-013-0964-x

    Article  CAS  PubMed  Google Scholar 

  60. Jones CJ, Thornback JR (2007) Diagnostic medicine. In: Medicinal applications of coordination chemistry. Royal Society of Chemistry, Cambridge, pp 101–200. doi:10.1039/9781847557759-00101

    Google Scholar 

  61. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  62. Wong RS (2011) Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res 30:87. doi:10.1186/1756-9966-30-87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Goodwin RA, Asmis TR (2009) Overview of systemic therapy for colorectal cancer. Clin Colon Rectal Surg 22(4):251–256. doi:10.1055/s-0029-1242465

    Article  PubMed  PubMed Central  Google Scholar 

  64. Erdem ZN, Schwarz S, Drev D, Heinzle C, Reti A, Heffeter P, Hudec X, Holzmann K, Grasl-Kraupp B, Berger W, Grusch M, Marian B (2017) Irinotecan upregulates fibroblast growth factor receptor 3 expression in colorectal cancer cells, which mitigates irinotecan-induced apoptosis. Trans Int Soc Cell 10(3):332–339. doi:10.1016/j.tranon.2017.02.004

    Google Scholar 

  65. Elvas F, Vangestel C, Pak K, Vermeulen P, Gray B, Stroobants S, Staelens S, Wyffels L (2016) Early prediction of tumor response to treatment: preclinical validation of 99mTc-duramycin. J Nucl Med 57(5):805–811. doi:10.2967/jnumed.115.168344

    Article  PubMed  Google Scholar 

  66. Luo R, Niu L, Qiu F, Fang W, Fu T, Zhao M, Zhang YJ, Hua ZC, Li XF, Wang F (2016) Monitoring apoptosis of breast cancer xenograft after paclitaxel treatment with 99mTc-labeled duramycin SPECT/CT. Mol Imaging. doi:10.1177/1536012115624918

    PubMed  PubMed Central  Google Scholar 

  67. Rahmanian N, Hosseinimehr SJ, Khalaj A (2016) The paradox role of caspase cascade in ionizing radiation therapy. J Biomed Sci 23(1):88. doi:10.1186/s12929-016-0306-8

    Article  PubMed  PubMed Central  Google Scholar 

  68. De Saint-Hubert M, Bauwens M, Mottaghy FM (2014) Molecular imaging of apoptosis for early prediction of therapy efficiency. Curr Pharm Des 20(14):2319–2328

    Article  PubMed  Google Scholar 

  69. Van de Wiele C, Vermeersch H, Loose D, Signore A, Mertens N, Dierckx R (2004) Radiolabeled annexin-V for monitoring treatment response in oncology. Cancer Biother Radiopharm 19(2):189–194. doi:10.1089/108497804323071968

    Article  PubMed  Google Scholar 

  70. Labi V, Erlacher M (2015) How cell death shapes cancer. Cell Death Dis 6:e1675. doi:10.1038/cddis.2015.20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Elvas F, Boddaert J, Vangestel C, Pak K, Gray B, Kumar-Singh S, Staelens S, Stroobants S, Wyffels L (2016) 99mTc-Duramycin SPECT imaging of early tumor response to targeted therapy: a comparison with 18F-FDG PET. J Nucl Med. doi:10.2967/jnumed.116.182014

    Google Scholar 

  72. Kostakoglu L, Goldsmith SJ (2003) 18F-FDG PET evaluation of the response to therapy for lymphoma and for breast, lung, and colorectal carcinoma. J Nucl Med 44(2):224–239

    PubMed  Google Scholar 

  73. Ben-Haim S, Ell P (2009) 18F-FDG PET and PET/CT in the evaluation of cancer treatment response. J Nucl Med 50(1):88–99. doi:10.2967/jnumed.108.054205

    Article  PubMed  Google Scholar 

  74. Chang JM, Lee HJ, Goo JM, Lee HY, Lee JJ, Chung JK, Im JG (2006) False positive and false negative FDG-PET scans in various thoracic diseases. Korean J Radiol 7(1):57–69. doi:10.3348/kjr.2006.7.1.57

    Article  PubMed  PubMed Central  Google Scholar 

  75. Ran S, Downes A, Thorpe PE (2002) Increased exposure of anionic phospholipids on the surface of tumor blood vessels. Cancer Res 62(21):6132–6140

    CAS  PubMed  Google Scholar 

  76. Galluzzi L, Vitale I, Vacchelli E, Kroemer G (2011) Cell death signaling and anticancer therapy. Front Oncol 1:1–18. doi:10.3389/fonc.2011.00005

    PubMed  PubMed Central  Google Scholar 

  77. Konstantinidis K, Whelan RS, Kitsis RN (2012) Mechanisms of cell death in heart disease. Arterioscler Thromb Vasc Biol 32(7):1552–1562. doi:10.1161/ATVBAHA.111.224915

    Article  CAS  PubMed  Google Scholar 

  78. Narula J, Zaret BL (2002) Noninvasive detection of cell death: from tracking epitaphs to counting coffins. J Nucl Cardiol 9(5):554–560

    Article  PubMed  Google Scholar 

  79. Musters RJ, Otten E, Biegelmann E, Bijvelt J, Keijzer JJ, Post JA, Op den Kamp JA, Verkleij AJ (1993) Loss of asymmetric distribution of sarcolemmal phosphatidylethanolamine during simulated ischemia in the isolated neonatal rat cardiomyocyte. Circ Res 73(3):514–523

    Article  CAS  PubMed  Google Scholar 

  80. Post JA, Clague JR, Langer GA (1993) Sarcolemmal phospholipid asymmetry and Ca fluxes on metabolic inhibition of neonatal rat heart cells. Am J Physiol 265(2 Pt 2):H461–H468

    CAS  PubMed  Google Scholar 

  81. Salerno M, Beller GA (2009) Noninvasive assessment of myocardial perfusion. Circulation 2(5):412–424. doi:10.1161/circimaging.109.854893

    PubMed  Google Scholar 

  82. Audi S, Li Z, Capacete J, Liu Y, Fang W, Shu LG, Zhao M (2012) Understanding the in vivo uptake kinetics of a phosphatidylethanolamine-binding agent 99mTc-duramycin. Nucl Med Biol 39(6):821–825. doi:10.1016/j.nucmedbio.2012.02.004

    Article  CAS  PubMed  Google Scholar 

  83. Taki J, Higuchi T, Kawashima A, Tait JF, Kinuya S, Muramori A, Matsunari I, Nakajima K, Tonami N, Strauss HW (2004) Detection of cardiomyocyte death in a rat model of ischemia and reperfusion using 99mTc-labeled annexin V. J Nucl Med 45(9):1536–1541

    CAS  PubMed  Google Scholar 

  84. Dumont EA, Hofstra L, van Heerde WL, van den Eijnde S, Doevendans PA, DeMuinck E, Daemen MA, Smits JF, Frederik P, Wellens HJ, Daemen MJ, Reutelingsperger CP (2000) Cardiomyocyte death induced by myocardial ischemia and reperfusion: measurement with recombinant human annexin-V in a mouse model. Circulation 102(13):1564–1568

    Article  CAS  PubMed  Google Scholar 

  85. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P (1996) Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest 74(1):86–107

    CAS  PubMed  Google Scholar 

  86. Kostin S, Pool L, Elsasser A, Hein S, Drexler HC, Arnon E, Hayakawa Y, Zimmermann R, Bauer E, Klovekorn WP, Schaper J (2003) Myocytes die by multiple mechanisms in failing human hearts. Circ Res 92(7):715–724. doi:10.1161/01.RES.0000067471.95890.5C

    Article  CAS  PubMed  Google Scholar 

  87. Tabas I, Seimon T, Timmins J, Li G, Lim W (2009) Macrophage apoptosis in advanced atherosclerosis. Ann N Y Acad Sci 1173(Suppl 1):E40–E45. doi:10.1111/j.1749-6632.2009.04957.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Andres V, Pello OM, Silvestre-Roig C (2012) Macrophage proliferation and apoptosis in atherosclerosis. Curr Opin Lipidol 23(5):429–438. doi:10.1097/MOL.0b013e328357a379

    Article  CAS  PubMed  Google Scholar 

  89. Liu Z, Larsen BT, Lerman LO, Gray BD, Barber C, Hedayat AF, Zhao M, Furenlid LR, Pak KY, Woolfenden JM (2016) Detection of atherosclerotic plaques in ApoE-deficient mice using 99mTc-duramycin. Nucl Med Biol 43(8):496–505. doi:10.1016/j.nucmedbio.2016.05.007

    Article  CAS  PubMed  Google Scholar 

  90. Broughton BR, Reutens DC, Sobey CG (2009) Apoptotic mechanisms after cerebral ischemia. Stroke 40(5):e331–e339. doi:10.1161/STROKEAHA.108.531632

    Article  PubMed  Google Scholar 

  91. Zhang Y, Stevenson GD, Barber C, Furenlid LR, Barrett HH, Woolfenden JM, Zhao M, Liu Z (2013) Imaging of rat cerebral ischemia-reperfusion injury using 99mTc-labeled duramycin. Nucl Med Biol 40(1):80–88. doi:10.1016/j.nucmedbio.2012.09.004

    Article  PubMed  Google Scholar 

  92. Audi SH, Jacobs ER, Zhao M, Roerig DL, Haworth ST, Clough AV (2015) In vivo detection of hyperoxia-induced pulmonary endothelial cell death using 99mTc-duramycin. Nucl Med Biol 42(1):46–52. doi:10.1016/j.nucmedbio.2014.08.010

    Article  CAS  PubMed  Google Scholar 

  93. Clough AV, Audi SH, Haworth ST, Roerig DL (2012) Differential lung uptake of 99mTc-hexamethylpropyleneamine oxime and 99mTc-duramycin in the chronic hyperoxia rat model. J Nucl Med 53(12):1984–1991. doi:10.2967/jnumed.112.108498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Johnson SE, Li Z, Liu Y, Moulder JE, Zhao M (2013) Whole-body imaging of high-dose ionizing irradiation-induced tissue injuries using 99mTc-duramycin. J Nucl Med 54(8):1397–1403. doi:10.2967/jnumed.112.112490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Medhora M, Haworth S, Liu Y, Narayanan J, Gao F, Zhao M, Audi S, Jacobs ER, Fish BL, Clough AV (2016) Biomarkers for radiation pneumonitis using noninvasive molecular imaging. J Nucl Med 57(8):1296–1301. doi:10.2967/jnumed.115.160291

    Article  PubMed  Google Scholar 

  96. Gao F, Fish BL, Moulder JE, Jacobs ER, Medhora M (2013) Enalapril mitigates radiation-induced pneumonitis and pulmonary fibrosis if started 35 days after whole-thorax irradiation. Radiat Res 180(5):546–552. doi:10.1667/RR13350.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular Imaging Center Antwerp, University of Antwerp, Universiteitsplein 1, Wilrijk, 2610, Belgium

    Filipe Elvas, Sigrid Stroobants & Leonie Wyffels

  2. Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium

    Filipe Elvas, Sigrid Stroobants & Leonie Wyffels

Authors
  1. Filipe Elvas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sigrid Stroobants
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leonie Wyffels
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leonie Wyffels.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elvas, F., Stroobants, S. & Wyffels, L. Phosphatidylethanolamine targeting for cell death imaging in early treatment response evaluation and disease diagnosis. Apoptosis 22, 971–987 (2017). https://doi.org/10.1007/s10495-017-1384-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10495-017-1384-0

Keywords

Search

Navigation