Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
권호 표지
DOI QR코드

DOI QR Code

[18F]Labeled 2-nitroimidazole derivatives for hypoxia imaging

  • Seelam, Sudhakara Reddy (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Lee, Yun-Sang (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Jeong, Jae Min (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine)
  • Received : 2016.11.18
  • Accepted : 2016.12.17
  • Published : 2016.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Imaging hypoxia using positron emission tomography (PET) is of great importance for cancer therapy. [$^{18}F$] Fluoromisonidazole (FMISO) was the first PET agent used for imaging tumor hypoxia. Various radiolabeled nitroimidazole derivatives such as [$^{18}F$]fluoroerythronitroimidazole (FETNIM), [$^{18}F$]1-${\alpha}$-D-(2-deoxy-2-fluoroarabinofuranosyl)-2-nitroimidazole(FAZA), 2-(2-nitroimidazol-1-yl)-N-(3,3,3-[18F]-trifluoropropyl)acetamide ([$^{18}F$]EF-3), [$^{18}F$]2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF-5), 3-[$^{18}F$]fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3,-triazol-1-yl)-propan-1-ol ([$^{18}F$]HX-4), and [$^{18}F$]fluoroetanidazole (FETA) were developed successively. However, these imaging agents still produce PET images with limited resolution; the lower blood flow in hypoxic tumors compared to normoxic tumors results in low uptake of the agents in hypoxic tumors. Thus, the development of better imaging agents is necessary.

Keywords

References

  1. de Rosales RTM, Arstad E, Blower PJ. Nuclear imaging of molecular processes in cancer. Targeted Oncol. 2009;4:183-197. https://doi.org/10.1007/s11523-009-0120-2
  2. Gambhir SS. Molecular imaging of cancer with positron emission tomography. Nature Rev Cancer. 2002;2:683-693. https://doi.org/10.1038/nrc882
  3. Harry VN, Semple SI, Parkin DE, Gilbert FJ. Use of new imaging techniques to predict tumour response to therapy. Lancet Oncol. 2010;11:92-102. https://doi.org/10.1016/S1470-2045(09)70190-1
  4. Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, Cheson BD, O'Shaughnessy J, Guyton KZ, Mankoff DA. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res. 2005;11:2785-2808. https://doi.org/10.1158/1078-0432.CCR-04-2626
  5. Lehtio K, Eskola O, Viljanen T, Oikonen V, Gronroos T, Sillanmaki L, Grenman R, Minn H. Imaging perfusion and hypoxia with PET to predict radiotherapy response in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2004;59:971-982. https://doi.org/10.1016/j.ijrobp.2003.12.014
  6. Lucignani G. PET imaging with hypoxia tracers: A must in radiation therapy. Eur J Nucl Med Mol Imaging. 2008;35:838-842. https://doi.org/10.1007/s00259-008-0740-2
  7. Rajendran JG, Schwartz DL, O'Sullivan J, Peterson LM, Ng P, Scharnhorst J, Grierson JR, Krohn KA. Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res. 2006;12:5435-5441. https://doi.org/10.1158/1078-0432.CCR-05-1773
  8. Koh W-J, Rasey JS, Evans ML, Grierson JR, Lewellen TK, Graham MM, Krohn KA, Griffin TW. Imaging of hypoxia in human tumors with [F-18] fluoromisonidazole. Int J Radiat Oncol Biol Phys. 1992;22:199-212. https://doi.org/10.1016/0360-3016(92)91001-4
  9. Valk PE, Mathis CA, Prados MD, Gilbert JC, Budinger TF. Hypoxia in human gliomas: Demonstration by PET with fluorine-18-fluoromisonidazole. J Nucl Med. 1992;33:2133-2137.
  10. Gomez FLG, Uehara T, Rokugawa T, Higaki Y, Suzuki H, Hanaoka H, Akizawa H, Arano Y. Synthesis and evaluation of diastereoisomers of 1,4,7-triazacyclononane-1, 4,7-tris-(glutaric acid) (NOTGA) for multimeric radiopharmaceuticals of gallium. Bioconjug Chem. 2012;23:2229-2238. https://doi.org/10.1021/bc300340g
  11. Sorger D, Patt M, Kumar P, Wiebe LI, Barthel H, Seese A, Dannenberg C, Tannapfel A, Kluge R, Sabri O. [18F] Fluoroazomycinarabinofuranoside (18FAZA) and [18F] Fluoromisonidazole (18FMISO): A comparative study of their selective uptake in hypoxic cells and PET imaging in experimental rat tumors. Nucl Med Biol. 2003;30:317-326. https://doi.org/10.1016/S0969-8051(02)00442-0
  12. Kachur AV, Dolbier Jr WR, Evans SM, Shiue C-Y, Shiue GG, Skov KA, Baird IR, James BR, Li A-R, Roche A, Koch CJ. Synthesis of new hypoxia markers EF1 and [$^{18}F$]-EF1. Appl Radiat Isot. 1999;51:643-650. https://doi.org/10.1016/S0969-8043(99)00096-2
  13. Mahy P, De Bast M, Leveque P, Gillart J, Labar D, Marchand J, Gregoire V. Preclinical validation of the hypoxia tracer 2-(2-nit roimidazol-1-yl)-N-(3, 3, 3-[$^{18}F$] trifluoropropyl) acetamide,[$^{18}F$] EF3. Eur J Nucl Med Mol Imaging. 2004;31:1263-1272.
  14. Ziemer L, Evans S, Kachur A, Shuman A, Cardi C, Jenkins W, Karp J, Alavi A, Dolbier W, Koch C. Noninvasive imaging of tumor hypoxia in rats using the 2-nitroimidazole 18F-EF5. Eur J Nucl Med Mol Imaging. 2003;30:259-266. https://doi.org/10.1007/s00259-002-1037-5
  15. Dubois LJ, Lieuwes NG, Janssen MHM, Peeters WJM, Windhorst AD, Walsh JC, Kolb HC, Ollers MC, Bussink J, Van Dongen GAMS, Van Der Kogel A, Lambin P. Preclinical evaluation and validation of [$^{18}F$$^{18}F$]HX4,a promising hypoxia marker for imaging. Proc Nat Acad Sci. 2011;108:14620-14625. https://doi.org/10.1073/pnas.1102526108
  16. Rasey JS, Hofstrand PD, Chin LK, Tewson TJ. Characterization of [18F] fluoroetanidazole, a new radiopharmaceutical for detecting tumor hypoxia. J Nucl Med. 1999;40:1072.
  17. Hoigebazar L, Jeong JM. Hypoxia Imaging Agents Labeled with Positron Emitters. Recent Results Cancer Res. 2013;194:285-299.
  18. Kelada OJ, Carlson DJ. Molecular imaging of tumor hypoxia with positron emission tomography. Radiat Res. 2014;181:335-349. https://doi.org/10.1667/RR13590.1
  19. Kizaka-Kondoh S, Konse-Nagasawa H. Significance of nitroimidazole compounds and hypoxia-inducible factor-1 for imaging tumor hypoxia. Cancer Sci. 2009;100:1366-1373. https://doi.org/10.1111/j.1349-7006.2009.01195.x
  20. Nunn A, Linder K, Strauss HW. Nitroimidazoles and imaging hypoxia. Eur J Nucl Med. 1995;22:265-280. https://doi.org/10.1007/BF01081524
  21. Rauth A, Melo T, Misra V. Bioreductive therapies: an overview of drugs and their mechanisms of action. Int J Radiat Oncol Biol Phys. 1998;42:755-762. https://doi.org/10.1016/S0360-3016(98)00302-2
  22. Takasawa M, Moustafa RR, Baron J-C. Applications of nitroimidazole in vivo hypoxia imaging in ischemic stroke. Stroke. 2008;39:1629-1637. https://doi.org/10.1161/STROKEAHA.107.485938
  23. Dubois L, Landuyt W, Haustermans K, Dupont P, Bormans G, Vermaelen P, Flamen P, Verbeken E, Mortelmans L. Evaluation of hypoxia in an experimental rat tumour model by 18F Fluoromisonidazole PET and immunohistochemistry. Br J Ca. 2004;91:1947-1954. https://doi.org/10.1038/sj.bjc.6602219
  24. Tang G, Wang M, Tang X, Gan M, Luo L. Fully automated one-pot synthesis of [$^{18}F$] fluoromisonidazole. Nucl Med Biol 2005;32:553-558. https://doi.org/10.1016/j.nucmedbio.2005.03.010
  25. Kumar P, Stypinski D, Xia H, McEwan AJB, Machulla HJ, Wiebe LI. Fluoroazomycin arabinoside (FAZA): Synthesis, 2H and 3H-labelling and preliminary biological evaluation of a novel 2-nitroimidazole marker of tissue hypoxia. J Label Compd Radiopharm. 1999;42:3-16. https://doi.org/10.1002/(SICI)1099-1344(199901)42:1<3::AID-JLCR160>3.0.CO;2-H
  26. Wiebe L. Radiohalogenated nitroimidazoles for single-photon scintigraphic imaging of hypoxic tissues. in Imaging of hypoxia: Tracer developments. Vol. 33, Ed. Machulla H-J. Springer Science & Business Media; 1999, pp155-169.
  27. Hoigebazar L, Jeong JM, Lee JY, Shetty D, Yang BY, Lee YS, Lee DS, Chung JK, Lee MC. Syntheses of 2-nitroimidazole derivatives conjugated with 1,4,7-triazacyclononane-N, N '-diacetic acid labeled with F-18 using an aluminum complex method for hypoxia imaging. J Med Chem. 2012;55:3155-3162. https://doi.org/10.1021/jm201611a
  28. Shetty D, Choi SY, Jeong JM, Lee JY, Hoigebazar L, Lee YS, Lee DS, Chung JK, Lee MC, Chung YK. Stable aluminium fluoride chelates with triazacyclononane derivatives proved by X-ray crystallography and $^{18}F$-labeling study. Chem Commun. 2011;47:9732-9734. https://doi.org/10.1039/c1cc13151f
  29. Shetty D, Jeong JM, Kim YJ, Lee JY, Hoigebazar L, Lee Y-S, Lee DS, Chung J-K. Development of a bifunctional chelating agent containing isothiocyanate residue for one step F-18 labeling of peptides and application for RGD labeling. Bioorg. Med. Chem. 2012;20:5941-5947. https://doi.org/10.1016/j.bmc.2012.07.050
  30. Hoigebazar L, Jeong JM, Choi SY, Choi JY, Shetty D, Lee Y-S, Lee DS, Chung J-K, Lee MC, Chung YK. Synthesis and characterization of nitroimidazole derivatives for 68Ga-labeling and testing in tumor xenografted mice. J Med Chem. 2010;53:6378-6385. https://doi.org/10.1021/jm100545a
  31. Hoigebazar L, Jeong JM, Hong MK, Kim YJ, Lee JY, Shetty D, Lee YS, Lee DS, Chung JK, Lee MC. Synthesis of 68Ga-labeled DOTA-nitroimidazole derivatives and their feasibilities as hypoxia imaging PET tracers. Bioorg Med Chem. 2011;19:2176-2181. https://doi.org/10.1016/j.bmc.2011.02.041
  32. Kizaka-Kondoh S, Inoue M, Harada H, Hiraoka M. Tumor hypoxia: A target for selective cancer therapy. Cancer Sci. 2003;94:1021-1028. https://doi.org/10.1111/j.1349-7006.2003.tb01395.x
  33. Aboagye E, Lewis A, Johnson A, Workman P, Tracy M, Huxham I. The novel fluorinated 2-nitroimidazole hypoxia probe SR-4554: Reductive metabolism and semiquantitative localisation in human ovarian cancer multicellular spheroids as measured by electron energy loss spectroscopic analysis. Br J Ca. 1995;72:312-318. https://doi.org/10.1038/bjc.1995.330
  34. Linder KE, Chan YW, Cyr JE, Malley MF, Nowotnik DP, Nunn AD. TcO (PnAO-1-(2-nitroimidazole))[BMS-181321], a new technetium-containing nitroimidazole complex for imaging hypoxia: synthesis, characterization, and xanthine oxidase-catalyzed reduction. J Med Chem. 1994;37:9-17. https://doi.org/10.1021/jm00027a002
  35. Chu T, Hu S, Wei B, Wang Y, Liu X, Wang X. Synthesis and biological results of the technetium-99m-labeled 4-nitroimidazole for imaging tumor hypoxia. Bioorg Med Chem Lett. 2004;14:747-749. https://doi.org/10.1016/j.bmcl.2003.11.017
  36. Li Z, Zhang J, Jin Z, Zhang W, Zhang Y. Synthesis and biodistribution of novel 99mTc labeled 4-nitroimidazole dithiocarbamate complexes as potential agents to target tumor hypoxia. Med Chem Comm. 2015;6:1143-1148. https://doi.org/10.1039/C5MD00042D
  37. Barthel H, Wilson H, Collingridge D, Brown G, Osman S, Luthra S, Brady F, Workman P, Price PM, Aboagye E. In vivo evaluation of $^{18}F$ fluoroetanidazole as a new marker for imaging tumour hypoxia with positron emission tomography. Br J Ca. 2004;90:2232-2242. https://doi.org/10.1038/sj.bjc.6601862
  38. Lee ST, Scott AM. Hypoxia positron emission tomography imaging with $^{18}F$-fluoromisonidazole. Semin Nucl Med. 2007:37:451-461. https://doi.org/10.1053/j.semnuclmed.2007.07.001
  39. Martin GV, Caldwell JH, Rasey JS, Grunbaum Z, Cerqueira M, Krohn KA. Enhanced binding of the hypoxic cell marker [$^3H$] fluoromisonidazole in ischemic myocardium. J Nucl Med. 1989;30:194-201.
  40. Rasey JS, Koh W-j, Evans ML, Peterson LM, Lawellen TK, Graham MM, Krohn KA. Quantifying regional hypoxia in human tumors with positron emission tomography of [$^{18}F$] fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys. 1996;36:417-428. https://doi.org/10.1016/S0360-3016(96)00325-2
  41. Bruehlmeier M, Roelcke U, Schubiger PA, Ametamey SM. Assessment of hypoxia and perfusion in human brain tumors using PET with $^{18}F$-fluoromisonidazole and $^{15}O-H2O$. J Nucl Med. 2004;45:1851-1859.
  42. Eschmann S-M, Paulsen F, Reimold M, Dittmann H, Welz S, Reischl G, Machulla H-J, Bares R. Prognostic impact of hypoxia imaging with $^{18}F$-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med. 2005;46:253-260.
  43. Guadagno JV, Donnan GA, Markus R, Gillard JH, Baron J-C. Imaging the ischaemic penumbra. Curr Opin Neurol. 2004;17:61-67. https://doi.org/10.1097/00019052-200402000-00011
  44. Markus R, Reutens D, Kazui S, Read S, Wright P, Pearce DC, Tochon-Danguy H, Sachinidis J, Donnan G. Hypoxic tissue in ischaemic stroke: Persistence and clinical consequences of spontaneous survival. Brain. 2004;127:1427-1436. https://doi.org/10.1093/brain/awh162
  45. Kubota K, Tada M, Yamada S, Hori K, Saito S, Iwata R, Sato K, Fakuda H, Ido T. Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue. Eur J Nucl Med. 1999;26:750-757. https://doi.org/10.1007/s002590050446
  46. Mahy P, De Bast M, de Groot T, Cheguillaume A, Gillart J, Haustermans K, Labar D, Gregoire V. Comparative pharmacokinetics, biodistribution, metabolism and hypoxia-dependent uptake of [$^{18}F$]-EF3 and [$^{18}F$]-MISO in rodent tumor models. Radiother Oncol. 2008;89:353-360. https://doi.org/10.1016/j.radonc.2008.06.008
  47. Krohn KA, Link JM, Mason RP. Molecular Imaging of Hypoxia. J Nucl Med. 2008;49(Suppl 2):129S-48S. https://doi.org/10.2967/jnumed.107.045914
  48. Chitneni SK, Palmer GM, Zalutsky MR, Dewhirst MW. Molecular imaging of hypoxia. J Nucl Med. 2011;52:165-168. https://doi.org/10.2967/jnumed.110.075663
  49. Gronroos T, Bentzen L, Marjamaki P, Murata R, Horsman MR, Keiding S, Eskola O, Haaparanta M, Minn H, Solin O. Comparison of the biodistribution of two hypoxia markers [$^{18}F$] FETNIM and [$^{18}F$] FMISO in an experimental mammary carcinoma. Eur J Nucl Med Mol Imaging. 2004;31:513-520. https://doi.org/10.1007/s00259-003-1404-x
  50. Zha Z, Zhu L, Liu Y, Du F, Gan H, Qiao J, Kung HF. Synthesis and evaluation of two novel 2-nitroimidazole derivatives as potential PET radioligands for tumor imaging. Nucl Med Biol. 2011;38:501-508. https://doi.org/10.1016/j.nucmedbio.2010.11.001
  51. Bejot R, Kersemans V, Kelly C, Carroll L, King RC, Gouverneur V. Pre-clinical evaluation of a 3-nitro-1, 2, 4-triazole analogue of [$^{18}F$] FMISO as hypoxia-selective tracer for PET. Nucl Med Biol. 2010;37:565-575. https://doi.org/10.1016/j.nucmedbio.2010.03.011
  52. Dubois L, Landuyt W, Cloetens L, Bol A, Bormans G, Haustermans K, Labar D, Nuyts J, Gregoire V, Mortelmans L. [$^{18}F$] EF3 is not superior to [$^{18}F$] FMISO for PET-based hypoxia evaluation as measured in a rat rhabdomyosarcoma tumour model. Eur J Nucl Med Mol Imaging. 2009;36:209-218. https://doi.org/10.1007/s00259-008-0907-x
  53. Busch TM, Hahn SM, Evans SM, Koch CJ. Depletion of tumor oxygenation during photodynamic therapy: detection by the hypoxia marker EF3 [2-(2-nitroimidazol-1 [H]-yl)-N-(3, 3, 3-trifluoropropyl) acetamide]. Cancer Res. 2000;60:2636-2642.
  54. Koch CJ. [1] Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5. Methods Enzymol. 2002;352:3-31.
  55. Troost EG, Laverman P, Kaanders JH, Philippens M, Lok J, Oyen WJ, van der Kogel AJ, Boerman OC, Bussink J. Imaging hypoxia after oxygenation-modification: comparing [$^{18}F$] FMISO autoradiography with pimonidazole immunohistochemistry in human xenograft tumors. Radiother Oncology. 2006;80:157-164. https://doi.org/10.1016/j.radonc.2006.07.023
  56. Fleming IN, Manavaki R, Blower PJ, West C, Williams KJ, Harris AL, Domarkas J, Lord S, Baldry C, Gilbert FJ. Imaging tumour hypoxia with positron emission tomography. Br J Ca. 2015;112:238-250. https://doi.org/10.1038/bjc.2014.610
  57. Piert M, Machulla H-J, Picchio M, Reischl G, Ziegler S, Kumar P, Wester HJ, Beck R, McEwan AJ, Weibe LI. Hypoxia-specific tumor imaging with $^{18}F$-fluoroazomycin arabinoside. J Nucl Med. 2005;46:106-113.
  58. Wyss MT, Honer M, Schubiger PA, Ametamey SM. NanoPET imaging of [$^{18}F$] fluoromisonidazole uptake in experimental mouse tumours. Eur J Nucl Med Mol Imaging. 2006;33:311-318. https://doi.org/10.1007/s00259-005-1951-4
  59. Cho H, Ackerstaff E, Carlin S, Lupu ME, Wang Y, Rizwan A, O’Donoghue J, Ling CC, Humm JL, Zanzonico PB. Noninvasive multimodality imaging of the tumor microenvironment: registered dynamic magnetic resonance imaging and positron emission tomography studies of a preclinical tumor model of tumor hypoxia. Neoplasia. 2009;11:247-259. https://doi.org/10.1593/neo.81360
  60. Sorensen M, Horsman MR, Cumming P, Munk OL, Keiding S. Effect of intratumoral heterogeneity in oxygenation status on FMISO PET, autoradiography, and electrode Po2 measurements in murine tumors. Int J Radiat Oncol Biol Phys. 2005;62:854-861. https://doi.org/10.1016/j.ijrobp.2005.02.044
  61. Liu RS, Chou TK, Chang CH, Wu CY, Chang CW, Chang TJ, Wang SJ, Lin WJ, Wang HE. Biodistribution, pharmacokinetics and PET imaging of [$^{18}F$]FMISO, [$^{18}F$] FDG and [$^{18}F$]FAc in a sarcoma- and inflammation-bearing mouse model. Nucl Med Biol. 2009;36:305-312. https://doi.org/10.1016/j.nucmedbio.2008.12.011
  62. Tochon-Danguy HJ, Sachinidis JI, Chan F, Chan JG, Hall C, Cher L, Stylli S, Hill J, Kaye A, Scott AM. Imaging and quantitation of the hypoxic cell fraction of viable tumor in an animal model of intracerebral high grade glioma using [$^{18}F$]fluoromisonidazole (FMISO). Nucl Med Biol. 2002;29:191-197. https://doi.org/10.1016/S0969-8051(01)00298-0
  63. Riedl CC, Brader P, Zanzonico P, Reid V, Woo Y, Wen B, Ling CC, Hricak H, Fong Y, Humm JL. Tumor hypoxia imaging in orthotopic liver tumors and peritoneal metastasis: a comparative study featuring dynamic $^{18}F$-MISO and $^{124I}IAZG$ PET in the same study cohort. Eur J Nucl Med Mol Imaging. 2008;35:39-46. https://doi.org/10.1007/s00259-007-0522-2
  64. Yang DJ, Wallace S, Cherif A, Li C, Gretzer MB, Kim EE, Podoloff DA. Development of F-18-labeled fluoroerythronitroimidazole as a PET agent for imaging tumor hypoxia. Radiology. 1995;194:795-800. https://doi.org/10.1148/radiology.194.3.7862981
  65. Reischl G, Dorow DS, Cullinane C, Katsifis A, Roselt P, Binns D, Hicks RJ. Imaging of tumor hypoxia with [124I] IAZA in comparison with [$^{18}F$]FMISO and [$^{18}F$]FAZA-first small animal PET results. J Pharm Pharma Sci. 2007;10:203-211.
  66. Seelam SR, Lee JY, Kim YJ, Lee Y-S, Jeong JM. Biodistribution and PET imaging of [$^{18}F$]FMISO in mousecolon cancer xenografted mice. J Radiopharm Mol Prob. 2015;1:137-144.
  67. Busk M, Horsman MR, Jakobsen S, Hansen KV, Bussink J, van der Kogel A, Overgaard J. Can hypoxia-PET map hypoxic cell density heterogeneity accurately in an animal tumor model at a clinically obtainable image contrast? Radiother Oncology. 2009;92:429-436. https://doi.org/10.1016/j.radonc.2009.08.026
  68. Gronroos T, Eskola O, Lehtio K, Minn H, Marjamaki P, Bergman J, Haaparanta M, Forsback S, Solin O. Pharmacokinetics of [$^{18}F$]FETNIM: A potential marker for PET. J Nucl Med. 2001;42(9):1397-1404.