Molecular imaging of apoptosis in vivo with scintigraphic and optical biomarkers - A status report

Anti-Cancer Agents in Medicinal Chemistry

Volumn 9, Issue 9, 2009, Pages 968-985

  Faust, Andreas ^a   Hermann, Sven ^b   Wagner, Stefan ^a   Haufe, Günther ^b   Schober, Otmar ^a   Schäfers, Michael ^b   Kopka, Klaus ^a,b  

^a UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^b UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

Annexin A5; Dansyl derived agents; Inhibitors of caspases; Molecular imaging; Optical imaging; Positron emission tomography PET; Single photon emission computed tomography SPECT; Targeted ligands

Indexed keywords

4 FLUOROBENZOATE F 18; 6 HYDRAZINONICOTINIC ACID ANNEXIN A5 TC 99M; BIOLOGICAL MARKER; CAMPTOTHECIN; CASPASE; CASPASE INHIBITOR; CYANINE DYE 5.5; CYCLOPHOSPHAMIDE; FLUORESCENT DYE; FLUORINE 18; GADOLINIUM PENTETATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INDIUM 111; IRON OXIDE; LIPOCORTIN 5; LIPOSOME; METHOXY ISOBUTYL ISONITRILE TECHNETIUM TC 99M; MOLECULAR MARKER; N [4 [[4 FLUOROBENZYLIDINE]AMINOOXY]BUTYL]MALEIMIDE F 18; PACLITAXEL; PERTECHNETIC ACID TC 99M; PHOSPHATIDYLSERINE; PHOSPHOLIPID; RADIOISOTOPE; RADIOLIGAND; RADIOPHARMACEUTICAL AGENT; SUPERPARAMAGNETIC IRON OXIDE; TECHNETIUM 99M; TRACER; UNCLASSIFIED DRUG; UNINDEXED DRUG;

APOPTOSIS; AUTOIMMUNE DISEASE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CELL COUNT; CELL LOSS; CELL PROLIFERATION; CELL TRANSFORMATION; CELL TYPE; CLINICAL TRIAL; DEGENERATIVE DISEASE; DOWN REGULATION; EMBRYO DEVELOPMENT; ENZYME ACTIVATION; ENZYME SUBSTRATE; GROWTH; HEART INFARCTION; HOMEOSTASIS; HUMAN; IN VIVO STUDY; METHODOLOGY; MOLECULAR IMAGING; NEOPLASM; NON INVASIVE MEASUREMENT; NONHUMAN; OUTER MEMBRANE; POSITRON EMISSION TOMOGRAPHY; REVIEW; SCINTIGRAPHY; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; STROKE; UPREGULATION;

APOPTOSIS; BIOLOGICAL MARKERS; HUMANS; RADIONUCLIDE IMAGING; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON;

EID: 73449102494     PISSN: 18715206     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152009789377754     Document Type: Review

References (153)

1. Bredesen, D.E. Genetic control of neural cell apoptosis. Perspect. Dev. Neurobiol., 1996, 3(2), 101-109.
2. Kerr, J.F.R.; Wyllie, A.H.; Currie, A.R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer, 1972, 26(4), 239-257.
3. Vogt, C. Untersuchungen über die Entwicklungsgeschichte der Geburtshelferkröte (Alytes obstertricians). Solothurn, 1842, 130.
4. Böhm, I.; Schild, H. Apoptosis: the complex scenario for a silent cell death. Mol. Imaging Biol., 2003, 5(1), 2-14.
5. Brown, J.M.; Attardi, L.D. The role of apoptosis in cancer development and treatment response. Nat. Rev. Cancer, 2005, 5(3), 231-237.
6. Mishra, N.C.; Kumar, S. Apoptosis: a mitochondrial perspective on cell death. Indian J. Exp. Biol., 2005, 43(1), 25-34.
7. Vaux, D.L.; Strasser, A. The molecular biology of apoptosis. Proc. Natl. Acad. Sci. USA, 1996, 93(6), 2239-2244.
8. Danial, N.N.; Korsmeyer, S.J. Cell death: critical control points. Cell, 2004, 116(2), 205-219.
9. Newmeyer, D.D.; Ferguson-Miller, S. Mitochondria: releasing power for life and unleashing the machineries of death. Cell, 2003, 112(4), 481-490.
10. Chinnaiyan, A.M.; Tepper, C.G.; Seldin, M.F. FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumour necrosis factor receptor-induced apoptosis. J. Biol. Chem., 1996, 271(9), 4961-4965.
11. O'Brian, T.; Linton, S.T. Design of caspase inhibitors as potential clinical agents; CRC Press: Boca Raton, 2009.
12. Cory, S.; Huang, D.C.; Adams, J.M. The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene, 2003, 22(53), 8590-8607.
13. Levine, B.; Kroemer, G. Autophagy in the pathogenesis of disease. Cell, 2008, 132(1), 27-42.
14. Reed, J.C. Bcl-2-family proteins and hematologic malignancies: history and future prospects. Blood, 2008, 111(7), 3322-3330.
15. Mani, K. Programmed cell death in cardiac myocytes: strategies to maximize post-ischemic salvage. Heart Fail. Rev., 2008, 13(2), 193-209.
16. Karaflou, M.; Lambrinoudaki, I.; Christodoulakos, G. Apoptosis in atherosclerosis: a mini-review. Mini Rev. Med. Chem., 2008, 8(9), 912-918.
17. Okouchi, M.; Ekshyyan, O.; Maracine, M.; Aw, T.Y. Neuronal apoptosis in neurodegeneration. Antioxid. Redox Signal., 2007, 9(8), 1059-1096.
18. Jänicke, R.U. MCF-7 breast carcinoma cells do not express caspase-3. Breast Cancer Res. Treat., 2009, [Epub ahead of print]. DOI 10.1007/s10549-008-0217-9.
19. Hebb, A.L.; Moore, C.S.; Bhan, V.; Robertson, G.S. Targeting apoptosis to treat multiple sclerosis. Curr. Drug Discov. Technol., 2008, 5(1), 75-77.
20. McCormick, A.L.; Roback, L.; Mocarski, E.S. HtrA2/Omi terminates cytomegalovirus infection and is controlled by the viral mitochondrial inhibitor of apoptosis (vMIA). PLoS Pathog., 2008, 9, e1000063.
21. Wang, D.; Lippard, S.J. Cellular processing of platinum anticancer drugs. Nat. Rev. Drug Discov., 2005, 4(4), 307-320.
22. Mita, M.; Tolcher, A.W. Novel apoptosis inducing agents in cancer therapy. Curr. Probl. Cancer, 2005, 29(1), 8-32.
23. Fadok, V.A.; Savill, J.S.; Haslett, C.; Bratton, D.L.; Doherty, D.E.; Campbell, P.A.; Henson, P.M. Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J. Immunol., 1992, 149(12), 4029-4035.
24. Hengartner, M.O. The biochemistry of apoptosis. Nature, 2000, 407(6805), 770-776.
25. Zwaal, R.F.A.; Schroit, A.J. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood, 1997, 89(4), 1121-1132.
26. Zwaal, R.F.A.; Comfurius, P.; Bevers, E.M. Surface exposure of phosphatidylserine in pathological cells. Cell. Mol. Life Sci., 2005, 62(9), 971-988.
27. Tait, J.F.; Gibson, D. Measurements of membrane phospholipid asymmetry in normal and sickle-cell erthyrocytes by means of annexin V binding. J. Lab. Clin. Med., 1994, 123(5), 741-748.
28. van Heerde, W.L.; de Groot, P.G.; Reutelingsperger, C.P.M. The complexity of the phospholipid binding protein annexin V. Thromb. Haemost., 1995, 73(2), 172-179.
29. Wood, B.L.; Gibson, D.F.; Tait, J.F. Increased phosphatidylserine exposure in sickle cell disease: flow cytometric measurement and clinical associations. Blood, 1996, 88(5), 1873-1880.
30. Martin, S.; Pombo, I.; Poncet, P.; David, B.; Arock, M.; Blank, U. Immunologic stimulation of mast cells leads to the reversible exposure of phosphatidylserine in the absence of apoptosis. Int. Arch. Allergy Immunol., 2000, 123(3), 249-258.
31. Yang, M.Y.; Chuang, H.; Chen, R.F.; Yang, K.D. Reversible phosphatidylserine expression on blood granulocytes related to membrane perturbation but not DNA strand breaks. J. Leukoc. Biol., 2002, 71(2), 231-237.
32. mTc annexin V. J. Nucl. Med., 1999, 40(1), 184-191.
33. Huerta, S.; Goulet, E.J.; Huerta-Yepez, S.; Livingston, E.H. Screening and detection of apoptosis. J. Surg. Res., 2007, 139(1), 143-156.
34. Jaattela, M. Multiple cell death pathways as regulators of tumour initiation and progression. Oncogene, 2004, 23(16), 2746-2756.
35. Susin, S.A.; Daugas, E.; Ravagnan, L.; Samejima, K.; Zamzami, N.; Loeffler, M.; Costantini, P.; Ferri, K.F.; Irinopoulou, T.; Prévost, M.C.; Brothers, G.; Mak, T.W.; Penninger, J.; Earnshaw, W.C.; Kroemer, G. Two distinct pathways leading to nuclear apoptosis. J. Exp. Med., 2000, 192(4), 571-580.
36. Barbier, S.; Chatre, L.; Bras, M.; Sancho, P.; Roué, G.; Virely, C.; Yuste, V.J.; Baudet, S.; Rubio, M.; Esquerda, J.E.; Sarfati, M.; Merle-Béral, H.; Susin, S.A. Caspase-independent type III programmed cell death in chronic lymphocytic leukemia: the key role of the F-actin cytoskeleton. Haematology, 2009, 94(4), 507-517.
37. Blankenberg, F.G. In vivo detection of apoptosis. J. Nucl. Med., 2008, 49(Suppl. 2), 81S-95S.
38. Pollack, M.; Phaneuf, S.; Dirks, A.; Leeuwenburgh, C. The role of apoptosis in the normal aging brain, skeletal muscle, and heart. Ann. N. Y. Acad. Sci., 2002, 959, 93-107.
39. Susin, S.A.; Zamzami, N.; Kroemer, G. Mitochondria as regulators of apoptosis: doubt no more. Biochim. Biophys. Acta, 1998, 1366(1-2), 151-165.
40. Zamzami, N.; Kroemer, G. The mitochondrion in apoptosis: how Pandora's box opens. Nat. Rev. Mol. Cell Biol., 2001, 2(1), 67-71.
41. 18F-fluorobenzyl triphenyl phosphonium. J. Nucl. Med., 2009, 50(5), 774-780.
42. Ravanat, C.; Archipoff, G.; Beretz, A.; Freund, G.; Cazenave, J.P.; Freyssinet, J.M. Use of annexin-V to demonstrate the role of phosphatidylserine exposure in the maintenance of haemostatic balance by endothelial cells. Biochem. J., 1992, 282(1), 7-13.
43. Vermes, I.; Haanen, C.; Steffens-Nakken, H.; Reutelingsperger, C.P.M. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J. Immunol. Methods, 1995, 184(1), 39-51.
44. Gerke, V.; Moss, S.E. Annexins: from structure to function. Physiol. Rev., 2002, 82(2), 331-371.
45. Benz, J.; Hofmann, A. Annexins: from structure to function. Biol. Chem., 1997, 378(3-4), 177-183.
46. Delmer, D.P.; Potikha, T.S. Structures and functions of annexins in plants. Cell. Mol. Life Sci., 1997, 53(6), 546-553.
47. Martin, S.J.; Reutelingsperger, C.P.M.; McGahon, A.J.; Radler, J.A.; van-Schie R.C.A.; LaFace, D.M.; Green D.R. Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl. J. Exp. Med., 1995, 182(5), 1545-1556.
48. Van den Eijnde, S.M.; Boshart, L.; Reutelingsperger, C.P.M.; DeZeeuw, C.I; Vermeij-Keers, C. Phosphatidylserine plasma membrane asymmetry in vivo: a pancellular phenomenon which alters during apoptosis. Cell Death Differ., 1997, 4(4), 311-316.
49. Laufer E.M.; Reutelingsperger, C.P.; Narula, J.; Hofstra, L. Annexin A5: an imaging biomarker of cardiovascular risk. Basic Res. Cardiol., 2008, 103(2), 95-104.
50. Li, X.; Link, J.M.; Stekhova, S.; Yagle, K.J.; Smith, C.; Krohn, K.A.; Tait, J.F. Site-Specific labelling of Annexin V with F-18 for apoptosis imaging. Bioconjug. Chem., 2008, 19(8), 1684-1688.
51. Laakko, T.; King, L.; Fraker, P. Versatility of merocyanine 540 for the flow cytometric detection of apoptosis in human and murine cells. J. Immunol. Methods. 2002, 261(1-2), 129-139.
52. Hanshaw, RG.; Lakshmi, C.; Lambert, T.N.; Johnson, J.R.; Smith, B.D. Fluorescent detection of apoptotic cells by using zinc coordination complexes with a selective affinity for membrane surfaces enriched with phosphatidylserine. ChemBioChem, 2005, 6(12), 2214-2220.
53. Bose, S.; Tuunainen, I.; Parry, M.; Medina, O.P.; Mancini, G.; Kinnunen, P.K. Binding of cationic liposomes to apoptotic cells. Analyt. Biochem. 2004, 331(2), 385-394.
54. Quinti, L.; Weissleder, R.; Tung, C-H. A fluorescent nanosensor for apoptotic cells. Nano Lett. 2006, 6(3), 488-490.
55. Laumonier, C.; Segers, J.; Laurent, S.; Michel, A.; Coppee, F.; Belayew, A.; Elst, L.V.; Muller, R. A new peptidic vector for molecular imaging of apoptosis, identified by phage display technology. J. Biomol. Screen., 2006, 11(5), 537-545.
56. Thapa, N.; Kim, S.; So, I.-S.; Lee B.-H.; Kwon, I.-C.; Choi, K.; Kim, S. Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis. J. Cell. Mol. Med., 2008, 12(5A), 1649-1660.
57. Shi, J.; Shi, Y.; Waehrens, L.N.; Rasmussen, J.T.; Heegard, C.W.; Gilbert, G.E. Lactadherin detects early phosphatidylserine exposure on immobilized leukemia cells undergoing programmed cell death. Cytometry Part A. 2006, 69(12), 1193-1201.
58. Jung, H.I.; Kettunen, M.I.; Davletov, B.; Brindle, K.M. Detection of apoptosis using the C2A domain of synaptotagmin I. Bioconjug. Chem. 2004, 15(5), 983-987.
59. Smith, C.; Gibson, D.F.; Tait, J.F. Transmembrane voltage regulates binding of annexin V and lactadherin to cells with exposed phosphatidylserine. BMC Biochem., 2009, 10, 5.
60. Lahorte, C.M.M.; Vanderheyden, J.L.; Steinmetz, N.; Van de Wiele, C.; Dierckx, R.A.; Slegers, G. Apoptosis-detecting radioligands: current state of the art and future perspectives. Eur. J. Nucl. Med. Mol. Imaging, 2004, 31(6), 887-919.
61. 99mTc-Annexin V. British J. Radiol., 2003, 76(908), 553-560.
62. Belhocine, T.Z.; Tait, J.F.; Vanderheyden, J.L.; Li, C.; Blankenberg, F.G. Nuclear medicine in the era of genomics and proteomics: lessons from annexin V. J. Proteome Res., 2004, 3(3), 345-349.
63. Boersma, H.H.; Bas, L.J.H.; Kietselaer, B.L.J.H.; Stolk, L.M.L.; Bennaghmouch, A.; Hofstra, L.; Narula, J.; Heidendal, G.A.K.; Reutlingsperger, C.P.M. Past, present, and future of annexin A5: from protein discovery to clinical applications. J. Nucl. Med., 2005, 46(12), 2035-2050.
64. Hofstra, L.; Liem, I.H.; Dumont, E.A.; Boersma, H.H.; van Heerde, W.L.; Doevendans, P.A.; DeMuinck, E.; Wellens, H.J.J.; Kemerink, G.J.; Reutelingsperger, C.P.M.; Heidendal, G.A. Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet, 2000, 356(9225), 209-212 and comments:
65. Strauss H.W.; Narula, J.; Blankenberg, F.G. Radioimaging to identify myocardial cell death and probably injury. Lancet, 2000, 356(9225), 180-181;
66. De Sutter, J.; Lahorte, C.; Taeymans, Y.; Dierckx, R.; Slegers, G. Cell death in myocardial infarction. Lancet, 2000, 356(9239), 1439-1440;
67. Reutelingsperger, C.; Hofstra, L. Visualisation of cell death. Lancet, 2000, 356(9246), 2014.
68. 18F-labelled annexin V: a PET tracer for apoptosis imaging. Eur. J. Nucl. Med. Mol. Imaging, 2004, 31(4), 469-474.
69. Reutelingsperger, C.P.M.; Dumont, E.; Thimister, P.W.; van Gederen, H.; Kenis, H.; van de Eijnde, S.; Heidendal, G.; Hofstra, L. Visualization of cell death in vivo with the annexin A5 imaging protocol. J. Immunol. Meth., 2002, 265(1-2), 123-132.
70. Kietselaer, B.L.J.H.; Hofstra, L.; Dumont, E.A.W.J.; Reutlingsperger, C.P.M.; Heidendal, G.A.K. The role of labeled Annexin A5 in imaging of programmed cell death. From animal to clinical imaging. Q. J. Nucl. Med., 2003, 47(4), 349-361.
71. Narula, J.; Acio, E.R.; Narula, N.; Samuels, L.E.; Fyfe, B.; Wood, D.; Fitzpatrick, J.M.; Raghunath, P.N.; Tomaszewski, J.E.; Kelly, C.; Steinmetz, N.; Green, A.; Tait, J.F.; Leppo, J.; Blankenberg, F.G.; Jain, D.; Strauss, H.W. Annexin-V imaging for noninvasive detection of cardiac allograft rejection. Nat. Med., 2001, 7(12), 1347-1352.
72. 99mTc-labeled annexin A5 in heart failure. J. Nucl. Med., 2007, 48(4), 562-567.
73. Van den Brande, J.M.; Koehler, T.C.; Zelinkova, Z.; Bennink, R.J.; te Velde, A.A.; ten Cate, F.J.; van Deventer, S.J.; Peppelenbosch, M.P.; Hommes, D.W. Prediction of antitumour necrosis factor clinical efficacy by real-time visualisation of apoptosis in patients with Crohn's disease. Gut, 2007, 56(4), 509-517.
74. Kietselaer, B.L.; Narula, J.; Hofstra, L. The annexin code: revealing endocarditis. Eur. Heart J., 2007, 28(8), 948.
75. 99mTc-recombinant human annexin v imaging for differential diagnosis of aseptic loosening and low-grade infection in hip and knee prostheses. J. Nucl. Med., 2009, 50(4), 534-537.
76. Rouzet, F.; Hernandez, M.D.; Hervatin, F.; Sarda-Mantel, L.; Lefort, A.; Duval, X.; Louedec, L.; Fantin, B.; Le Guludec, D.; Michel, J.B. Technetium 99m-Labelled annexin v scintigraphy of platelet activation in vegetations of experimental endocarditis. Circulation, 2008, 117(6), 781-789.
77. Virmani, R.; Burke, A.P.; Farb, A.; Kolodgie F.D. Pathology of the unstable plaque. Proc. Cardiovasc. Dis., 2002, 44(5), 349-356.
78. Kolodgie, F.D.; Petrov, A.; Virmani, R.; Narula, N.; Verjans, J.W.; Weber, D.K.; Hartung, D.; Steinmetz, N.; Vanderheyden, J.L.; Vannan, M.A.; Gold, H.K.; Reutelingsperger, C.P.; Hofstra, L.; Narula, J. Targeting of apoptotic macrophages and experimental atheroma with radiolabelled Annexin V: a technique with potential for noninvasive imaging of vulnerable plaque. Circulation, 2003, 108(25), 3134-3139.
79. 99mTc-annexin V imaging for in vivo detection of atherosclerotic lesions in porcine coronary arteries. J. Nucl. Med., 2005, 46(7), 1186-1193.
80. Kietselaer, B.L.; Reutelingsperger, C.P.; Heidendal, G.A.; Daemen, M.J.; Mess, W.H.; Hofstra, L.; Narula, J. Noninvasive detection of plaque instability with use of radiolabeled annexin A5 in patients with carotidartery atherosclerosis. N. Engl. J. Med., 2004, 350(14), 1472-1473.
81. Van de Wiele, C.; Lahorte, C.; Vermeersch, H.; Loose, D.; Mervillie, K.; Steinmetz, N. D.; Vanderheyden, J.L.; Cuvelier, C.A.; Slegers, G.; Dierck, R.A. Quantitative tumour apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography. J. Clin. Oncol., 2003, 21(18), 3483-3487.
82. 99mTc recombinant human Annexin V in human tumours after one course of chemotherapy as a predictor of tumour response and patient prognosis. Clin. Cancer Res., 2002, 8(9), 2766-2774.
83. 99mTc-HYNIC-rh-annexin-V scintigraphy: visual and quantitative evaluation of early treatment-induced apoptosis to predict treatment outcome. Nucl. Med. Commun., 2008, 29(1), 39-44.
84. mTc EC annexin V: preliminary clinical study targeting apoptosis in breast tumours. Appl. Radiat. Isot., 2008, 66(9), 1175-1182.
85. 3-HIS-AnxV: improved imaging of apoptosis in vivo. Nuklearmedizin, 2009, 48, A58.
86. Tait, J.F.; Smith, C.; Levashova, Z.; Patel, B.; Blankenberg, F.G.; Vanderheyden, J.L. Improved detection of cell death in vivo with annexin V radiolabeled by site-specific methods. J. Nucl. Med., 2006 47(9), 1546-1553 and comment:
87. Eisenhut, M.; Haberkorn, U. Molecular position of radiolabels and its impact on functional integrity of proteins. J. Nucl. Med., 2006, 47(9), 1400-1402.
88. 99mTc-labelled annexin V fragments: a potential SPECT radiopharmaceutical for imaging cell death. Nucl. Med. Biol., 2006, 33(5), 635-643.
89. Wen, X.; Wu, Q.P.; Ke, S.; Wallace, S.; Charnsangavej, C.; Huang, P.; Liang, D.; Chow, D.; Li, C. Improved radiolabelling of PEGylated protein: PEGylated annexin V for noninvasive imaging of tumour apoptosis. Cancer Biother. Radiopharm., 2003, 18(5), 819-827.
90. 111In-labeled annexin V. J. Nucl. Med., 2004, 45(1), 108-115.
91. Li, X.; Link, J.M.; Stekhova, S.; Yagle, K.J.; Smith, C.; Krohn, K.A.; Tait, J.F. Site-specific labeling of annexin V with F-18 for apoptosis imaging. Bioconjug. Chem., 2008, 19(8), 1684-1688.
92. Zijlstra, S.; Gunawan, J.; Burchert, W. Synthesis and evaluation of a Fluorine-18 labelled recombinant annexin-V derivative, for idenfication and quantification of apoptotic cells with PET. Appl. Radiat. Isot., 2003, 58(2), 201-207.
93. Koopman, G.; Reutelingsperger, C.P.M.; Kuijten, G.A.M.; Keehnen, R.M.J.; Pals, S.T.; vanOers, M.H.J. Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis. Blood, 1994, 84(5), 1415-1420.
94. Schellenberger, E.A.; Weissleder, R.; Josephson, L. Optimal modification of annexin V with fluorescent dyes. ChemBioChem., 2004, 5(3), 271-274.
95. Vermes, I.; Haanen, C., Steffens-Nakken, H.; Reutelingsperger, C.P.M. A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J. Immunol. Methods, 1995, 184(1), 39-51.
96. Vermes, I.; Haanen, C.; Reutelingsperger, C.P.M. Flow cytometry of apoptotic cell death. J. Immunol. Methods, 2000, 243(1-2), 167-190.
97. Derby, E.; Reddy, V.; Kopp, W.; Nelson, E.; Baseler, M.; Sayers, T.; Malyguine, A. Three-color flow cytometric assay for the study of the mechanisms of cell-mediated cytotoxicity. Immunol. Lett., 2001, 78(1), 35-39.
98. Malyguine, A.; Derby, E.; Brooks, A.; Reddy, V.; Baseler, M.; Sayers, T. Study of diverse mechanisms of cell-mediated cytotoxicity in gene-targeted mice using flow cytometric cytotoxicity assay. Immunol. Lett., 2002, 83(1), 55-59.
99. Petrovsky, A.; Schellenberger, E.; Josephson, L.; Weissleder, R.; Bogdanov, A. Near-Infrared Fluorescent Imaging of Tumour Apoptosis. Cancer Res., 2003, 63(8), 1936-1942.
100. Ntziachristos, V.; Schellenberger, E.A.; Ripoll, J.; Yessayan, D.; Graves, E.; Bogdanov, A.; Josephson, L.; Weissleder, R. Visualization of antitumour treatment by means of fluorescence molecular tomography with an annexin V-Cy5.5 conjugate. Proc. Natl. Acad. Sci. USA, 2004, 101(33), 12294-12299.
101. Medarova, Z.; Bonner-Weir, S.; Lipes, M.; Moore, A. Imaging Cell Death With a Near-Infrared Probe. Diabetes, 2005, 54(6), 1780-1788.
102. Zhao, M.; Beauregard, D.A.; Loizou, L.; Davletov, B.; Brindle, K. Non-Invasive Detection of Apoptosis Using Magnetic Resonance Imaging and a Targeted Contrast Agent. Nat. Med., 2001, 7(11), 1241-1244.
103. Jung, H.I.; Kettunen, M.I.; Davletov, B.; Brindle, K.M. Detection of Apoptosis Using the C2A Domain of Synaptotagmin I. Bioconjug. Chem. 2004, 15(5), 983-987.
104. Huber, M.M.; Staubli, A.B.; Kustedjo, K.; Gray, M.H.; Shih, J.; Fraser, S.E.; Jacobs, R.E.; Meade, T.J. Fluorescently detectable magnetic resonance imaging agents. Bioconjug. Chem., 1998, 9(2), 242-249.
105. Modo, M.; Cash, D.; Mellodew, K.; Williams, S.C.; Fraser, S.E.; Meade, T.J.; Price, J.; Hodges, H. Tracking transplanted stem cell migration using bifunctional contrast agent-enhanced magnetic resonance imaging. Neuroimage, 2002, 17(2), 803-811.
106. Mulder, W.J.; Strijkers, G.J.; Griffioen, A.W.; van Bloois, L.; Molema, G.; Storm, G.; Koning, G.A.; Nicolay, K. A liposomal system for contrast-enhanced magnetic resonance imaging of molecular targets. Bioconjug. Chem., 2004, 15(4), 799-806.
107. Mulder, W.J.; Strijkers, G.J.; Habets, J.W.; Bleeker, E.J.; van der Schaft, D.W.; Storm, G.; Koning, G.A.; Griffioen, A.W.; Nicolay, K. MR Molecular imaging and fluorescence microscopy for identification of activated tumour endothelium using a bimodal lipidic nanoparticle. FASEB J., 2005, 19(14), 2008-2010.
108. Schellenberger, E.A.; Sosnovik, D.; Weissleder, R.; Josephson, L. Magneto/optical annexin v, a multimodal protein. Bioconjug. Chem., 2004, 15(5), 1062-1067.
109. Sosnovik, D.E.; Schellenberger, E.A.; Nahrendorf, M.; Novikov, M.S.; Matsui, T.; Dai, G.; Reynolds, F.; Grazette, L.; Rosenzweig, A.; Weissleder, R.; Josephson, L. Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle. Magn. Reson. Med., 2005, 54(3), 718-724.
110. van Tilborg, G.A.F.; Mulder, W.J.M.; Chin, P.T.K.; Storm, P.; Reutelingsperger, C.P.M.; Nicolay, K.; Strijkers, G.J. Annexin A5-Conjugated quantum dots with a paramagnetic lipidic coating for the multimodal detection of apoptotic cells. Bioconjug. Chem., 2006, 17(4), 865-868.
111. van Tilborg, G.A.F.; Mulder, W.J.M.; Deckers, N.; Storm, G. Reutelingsperger, C.P.M.; Strijkers, G.J.; Nicolay, K. Annexin A5-Functionalized bimodal lipid-based contrast agents for the detection of apoptosis. Bioconjug. Chem., 2006, 17(3), 741-749.
112. van Tilborg, G.A.; Geelen, T.; Duimel, H.; Bomans, P.H.; Frederik, P.M.; Sanders, H.M.; Deckers, N.M.; Deckers, R.; Reutelingsperger, C.P.M.; Strijkers, G.J.; Nicolay, K. Internalization of annexin A5-functionalized iron oxide particles by apoptotic Jurkat cells. Contrast Media Mol. Imaging, 2009, 4(1), 24-32.
113. Kenis H, van Genderen H, Bennaghmouch A. Cell surface-expressed phosphatidylserine and annexin A5 open a novel portal of cell entry. J. Biol. Chem., 2004, 279(50), 52623-52629.
114. Oling F, Santos JSDO, Govorukhina N. Structure of membrane-bound annexin A5 trimers: a hybrid Cryo-EM-X-ray crystallography study. J. Mol. Biol., 2000, 304(4), 561-573.
115. Nicholson, D.W.; Thornberry, N.A. Caspases: Killer proteases. Trends Biochem. Sci., 1997, 22(8), 299-306.
116. Waterhouse, N.J.; Trapani, J.A. CTL: Caspase terminate life, but that's not the whole story. Tissue Antigens, 2002, 59(3), 175-183.
117. Martinon, F.; Burns, K.; Tschopp, J. The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol. Cell., 2002, 10(2), 417-426.
118. Jimbo, A.; Fujita, E.; Kouroku. Y.; Ohnishi, J.; Inohara, N.; Kuida, K.; Sakamaki, K.; Yonehara, S.; Momoi, T. ER stress induces caspase-8 activation, stimulating cytochrom C release and caspase-9 activation. Exp. Cell Res., 2003, 283(2), 156-166.
119. Nakagawa, T.; Zhu, H.; Morishima, N.; Li, E.; Xu, J.; Yankner, B.A.; Yuan, J. Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature, 2000, 403(6765), 98-103.
120. Linton, S.D. Caspase inhibitors: A pharmaceutical industry perspective. Curr. Top. Med. Chem., 2005, 5(16), 1697-1717.
121. O'Brian, T.; Lee, D. Prospects for caspase inhibitors. Mini Rev. Med. Chem., 2004, 4(2), 153-165.
122. Haberkorn, U.; Kinscherf, R.; Krammer, P.H.; Mier, W.; Eisenhut, M. Investigation of a potential scintigraphic marker of apoptosis: radioiodinated Z-Val-Ala-DL-Asp(O-methyl)-fluoromethyl ketone. Nucl. Med. Biol., 2001, 28(7), 793-798.
123. Slee, E.A.; Zhu, H.; Chow, S.C.; MacFarlane, M.; Nicholson, D.W.; Cohen, G.M. Benzyloxycarbonyl-Val-Ala-Asp(OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32. Biochem. J., 1996, 315(Pt1), 21-24.
124. 131I-Labelled peptides as caspase substrates for apoptosis imaging. J. Nucl. Med., 2005, 46(6), 1066-1074.
125. Lee, D.; Long, S. A.; Murray, J. H.; Adams, J. L.; Nuttall, M. E.; Nadeau, D. P.; Kikly, K.; Winkler, J. D.; Sung, C. M.; Ryan, M. D.; Levy, M. A.; Keller, P. M.; DeWolf, W. E. Potent and selective nonpeptide inhibitors of caspases 3 and 7. J. Med. Chem., 2001, 44(12), 2015-2026.
126. Lee, D.; Long, S. A.; Adams, J. L.; Chan, G.; Vaidya, K. S.; Francis, T. A.; Kikly, K.; Winkler, J. D.; Sung, C. M.; Debouck, C.; Richardson, S.; Levy, M. A.; DeWolf, W. E., Jr.; Keller, P. M.; Tomaszek, T.; Head, M. S.; Ryan, M. D.; Haltiwanger, R. C.; Liang, P. H.; Janson, C. A.; McDevitt, P. J.; Johanson, K.; Concha, N. O.; Chan, W.; Abdel-Meguid, S. S.; Badger, A. M.; Lark, M. W.; Nadeau, D. P.; Suva, L. J.; Gowen, M.; Nuttall, M. E. Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionality. J. Biol. Chem., 2000, 275(21), 16007-16014.
127. a) Podichetty, A. K.; Faust, A.; Kopka, K.; Wagner, S.; Schober, O.; Schäfers, M.; Haufe, G. Fluorinated isatin derivatives. Part 1. New potent effector caspase inhibitors to target apoptosis. Bioorg. Med. Chem., 2009, 17(7), 2680-2688.
128. b) Podichetty, A.K.; Wagner, S.; Faust, A.; Schäfers, M.; Kopka, K.; Haufe, G. Fluorinated Isatin Derivatives. Part 1. New side-chain fluro-functionalized pyrrolidinyl sulfonyl isatins as potent caspase-3 and -7 inhibitors. Future Med. Chem., 2009, 1, 969-989.
129. Kopka, K.; Faust, A.; Keul, P.; Wagner, S.; Breyholz, H.J.; Höltke, C.; Schober, O.; Schäfers, M.; Levkau, B. 5-pyrrolidinylsulfonyl isatins as a potential tool for the molecular imaging of caspases in apoptosis. J. Med. Chem., 2006, 49(23), 6704-6715.
130. Chu, W.; Zhang, J.; Zeng, C.; Rothfuss, J.; Tu, Z.; Chu, Y.; Reichert, D.E.; Welch, M.J.; Mach, R.H. N-benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: synthesis, in vitro activity, and molecular modeling studies. J. Med. Chem., 2005, 48(24), 7637-7647.
131. Podichetty, A. K.; Wagner, S.; Schröer, S.; Faust, A. Schäfers, M.; Schober, O.; Kopka, K.; Haufe, G. Fluorinated Isatin Derivatives. Part 2. New N-substituted 5-pyrrolidinylsulfonyl isatins as potential tools for molecular imaging of caspases in apoptosis. J. Med. Chem., 2009, 52(11), 3484-3495.
132. 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis. Bioorg. Med. Chem. Lett., 2006, 16(19), 5041-5046.
133. b) Chen, D.L.; Zhou, D.; Chu, W.; Herrbrich, P.E.; Jones, L.A.; Rothfuss, J.M.; Engle, J.T.; Geraci, M.; Welch, M.J.; Mach, R.H. Comparison of radiolabelled isatin analogs for imaging apoptosis with positron emission tomography. Nucl. Med. Biol., 2009, 36(6), 651-658.
134. 18F]CbR) as potential positron emission tomography-compatible apoptosis imaging agent. Q. J. Nucl. Med. Mol. Imaging., 2007, 51(1), 67-73.
135. Ytrehus, K. The ischemic heart - experimental models. Pharmacol. Res., 2000, 42(3), 193-203.
136. 18F]fluoro-ethylazide. J. Med. Chem., 2008, 51(24), 8057-8067.
137. 11C]WC-98. Org. Biomol. Chem., 2009, 7(7), 1337-1348.
138. 99mTc-Labelled C2A Domain of Synaptotagmin I as a Target-Specific Molecular Probe for Noninvasive Imaging of Acute Myocardial Infarction. J. Nucl. Med., 2006, 47(8), 1367-1374.
139. Zhao, M.; Beauregard, D.A.; Loizou, L.; Davletov, B.; Brindle, K.M. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Nat. Med., 2001, 7(11), 1241-1244.
140. Krishnan, A.S.; Neves, A.A.; de Backer, M.M.; Hu, D.E.; Cavletov, B.; Kettunen, M.I.; Brindle, K.I. Detection of cell death in tumours by using MR imaging and a gadolinium-based targeted contrast agent. Radiology, 2008, 246(3), 854-862.
141. Weissleder, R. A clearer vision for in vivo imaging. Nat. Biotechnol., 2001, 19(4), 316-317.
142. Shao, R.; Xiong, C.; Wen, X.; Gelovani, R.G.; Li, C. Targeting phosphatidylserine on apoptotic cells with phages and peptides selected from a bacteriophage display library. Mol. Imaging, 2007, 6(6), 417-426.
143. Cohen, A.; Ziv, I.; Aloya, T.; Levin, G.; Kidron, D.; Grimberg, H.; Reshef, A.; Shirvan, A. Monitoring of chemotherapy-induced cell death in melanoma tumours by N,N-didansyl-L-cystine. Technol. Cancer Res. Treat., 2007, 6(3), 221-234.
144. Aloya, R.; Grimberg, H.; Reshef, A.; Levin, G.; Kidron, D.; Cohen, A.; Ziv, I. Molecular imaging of cell death in vivo by a novel small molecule probe. Apoptosis, 2006, 11(12), 2089-2101.
145. Damianovich, M.; Ziv, I.; Heyman, S.N.; Rosen, S.; Shina, A.; Kidron, D.; Aloya, T.; Grimberg, H.; Levin, G.; Reshef, A.; Bentolila, A.; Cohen, A.; Shirvan, A. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis. Eur. J. Nucl. Med. Mol. Imaging, 2006, 33(3), 281-291.
146. Reshef, A.; Shirvan, A.; Grimberg, H.; Levin, G.; Cohen, A.; Mayk, A.; Kidron, D.; Djaidetti, R.; Melamed, E.; Ziv, I. Novel molecular imaging of cell death in experimental cerebral stoke. Brain Res., 2007, 1144, 156-164.
147. Reshef, A.; Shirvan, A.; Waterhouse, R.N.; Grimberg, H.; Levin, G.; Cohen, A.; Ulysse, L.G.; Friedman, G.; Antoni, G.; Ziv, I. Molecular imaging of neurovascular cell death in experimental cerebral stroke by PET. J. Nucl. Med., 2008, 49(9), 1520-1528.
148. Reshef, A.; Shirvan, A.; Shohami, E.; Grimberg, H.; Levin, G.; Cohen, A.; Trembovler, V.; Ziv, I. Targeting cell death in vivo in experimental traumatic brain injury by a novel molecular probe. J. Neurotrauma, 2008, 25(6), 569-580.
149. Zeng, W.; Yao, L.; Townsend, D.; Kabalka, G.; Wall, J.; Le Puil, M.; Biggerstaff, J.; Miao, W. Synthesis, biological evaluation and radiochemical labelling of a dansylhydrazone derivative as a potential imaging agent for apoptosis. Bioorg. Med. Chem. Lett., 2008, 18(12), 3573-3577.
150. Grimberg, H.; Levin, G.; Shirvan, A.; Cohen, A.; Yogev-Falach, M.; Reshef, A.; Ziv, I. Monitoring of tumour response to chemotherapy in vivo by a novel small-molecule detector of apoptosis. Apoptosis, 2009, 14(3), 257-267.
151. 18F-fluorobenzyl triphenylphosphonium cation. Eur. J. Nucl. Med. Mol. Imaging, 2007, 34(12), 2057-2065.
152. 18F-fluorobenzyl triarylphosphonium
153. Wunder, A.; Klohs, J.; Dirnagl, U. Non-invasive visualization of CNS inflammation with nuclear and optical imaging. Neuroscience, 2009, 158(3), 1161-1173.