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Radiopharmaceuticals for Imaging Hypoxia

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Current Directions in Radiopharmaceutical Research and Development

Part of the book series: Developments in Nuclear Medicine ((DNUM,volume 30))

Abstract

The purpose of this article is to briefly review recent research on radiolabeled agents designed for the purpose of imaging tissue hypoxia in vivo. The text of this article will present a broad brush summary of the subject matter with more detailed information contained in the literature sources referenced. Another review of this subject area has recently been published elsewhere and may offer the reader the chance to gain additional insights into work performed in this area of research [1].

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References

  1. Nunn A, Linder K, Strauss HW. Nitroimidazoles and imaging hypoxia. Eur J Nucl Med 1995;22:265–280.

    Article  PubMed  CAS  Google Scholar 

  2. Ehlry, AM, editor. Determination of tissue oxygen pressure in patients. Oxford: Pergamon Press, 1983.

    Google Scholar 

  3. Vaupel P, Kallinowski F, Okunieff P. Blood flow, oxygen consumption and tissue oxygenation of human tumors. In: J Piiper et al., editors. Oxygen transport to tissue XII. New York: Plenum Press, 1990: 895–905.

    Google Scholar 

  4. Jones DF, Aw TY, Shan X, Tribble DL. Characteristics of hypoxic cells that enhance their susceptibility to chemical injury. In: Adams GE, Breccia A, Fielden EM, Wardman P, editors. Selective activation of drugs by redox processes. New York: Plenum Press, 1990: 1–9.

    Chapter  Google Scholar 

  5. Connett RJ, Honig CR, Gayeski TEJ, Brooks GA. Defining hypoxia: a systems view of V02, glycolysis, energetics, and intracellular P02. J Appl Physiol 1990; 68: 833–842.

    PubMed  CAS  Google Scholar 

  6. Weiss JN, Shieh RC. Potassium loss during myocardial ischaemia and hypoxia: does lactate efflux play a role? Cardiovascular Res 1994; 28: 1125–32.

    Article  CAS  Google Scholar 

  7. Wilde AAM, Aksnes G. Myocardial potassium loss and cell depolarisation in ischaemia and hypoxia. Cardiovascular Res 1995; 29: 1–15.

    CAS  Google Scholar 

  8. Zhang XQ, Pang L, Eyzaguirre C. Effects of hypoxia on the intracellular K+ of clustered and isolated glomus cells of mice and rats. Brain Res 1995; 676: 413–420.

    Article  PubMed  CAS  Google Scholar 

  9. Brown JM, Giaccia AJ. Tumour hypoxia: the picture has changed in the 1990’s. Int J Radiat Biol 1994; 65: 95–102.

    Article  PubMed  CAS  Google Scholar 

  10. Denekamp J, Rojas A. Multifactorial approaches to overcoming clinical radioresistance. In: Kogelnik HD, editor. Progress in radio-oncology V. Bologna: Monduzzi Editore, 1995: 9–19.

    Google Scholar 

  11. Vaupel P, Schienger C, Knoop C, Höckel M. Oxygenation of human tumors: evaluation of tissue oxygen distribution in breast cancers by computerized 02 tension measurements. Cancer Res 1991; 51:3316–3322.

    PubMed  CAS  Google Scholar 

  12. Höckel M, Schienger C, Knoop C, Vaupel P. Oxygenation of carcinomas of the uterine cervix: evaluation by computerized 02 tension measurements. Cancer Res 1991; 51:6098–6102.

    PubMed  Google Scholar 

  13. Nordsmark, M, Bentzen SM, Overgaard J. Measurement of human tumour oxygenation status by a Polarographic needle electrode: an analysis of inter- and intratumour heterogeneity. Acta Oncol. 1994; 33: 383–389.

    Article  PubMed  CAS  Google Scholar 

  14. Gatenby RA, Kessler HB, Rosenblum JS, et al. Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys 1988; 14: 831–838.

    Article  PubMed  CAS  Google Scholar 

  15. Brown JM, Sum BG. Hypoxia-specific cytotoxins in cancer therapy. Semin Radiat Oncol 1995; 6: 22–36.

    Article  Google Scholar 

  16. Edwards DI. Nitroimidazole drugs — action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother 1993; 31: 9–20.

    Article  PubMed  CAS  Google Scholar 

  17. Kedderis GL, Miwa GT. The metabolic activation of nitroheterocyclic therapeutic agents. Drug Metab Rev 1988; 19: 33–62.

    Article  PubMed  CAS  Google Scholar 

  18. Woodrooffe ATM, Bayliss MK, Park GR. The effects of hypoxia on drug-metabolising enzymes. Drug Metab Rev 1995; 27: 471–495.

    Article  PubMed  CAS  Google Scholar 

  19. Whitmore GF, Varghese AJ. The biological properties of reduced nitroheterocyclics and possible underlying biochemical mechanisms. Biochem Pharmacol 1986; 35: 97–103.

    Article  PubMed  CAS  Google Scholar 

  20. Biaglow JE, Varnes ME, Roizen-Towle L, et al. Biochemistry of reduction of nitroheterocycles. Biochem Pharmacol 1986; 35: 77–90.

    Article  PubMed  CAS  Google Scholar 

  21. Breccia A, Cavalleri B, Adams GE, editors. Nitroimidazoles: chemistry, pharmacology and clinical application. New York: Plenum Press, 1982.

    Google Scholar 

  22. Kirkpatrick DL. Bioreductive antineoplastic agents. Drugs of Today 1990; 26: 91–108.

    CAS  Google Scholar 

  23. Olive PL, Durand RE. Misonidazole binding in SCCVII tumors in relation to the tumor blood supply. Int J Radiat Oncol Biol Phys 1989; 16: 755–761.

    Article  PubMed  CAS  Google Scholar 

  24. Overgaard J, Sand Hansen H, Andersen AP, et al. Misonidazole combined with split-course radiotherapy in the treatment of invasive carcinoma of larynx and pharynx: report from the DAHANCA 2 study. Int J Radiat Oncol Biol Phys 1989; 16: 1065–1068.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

  26. Martin, GV, Caldwell JH, Graham, MM et al. Noninvasive detection of hypoxic myocardium using fluorine-18-fluoromisonidazole and positron emission tomography. J Nucl Med 1992; 33: 2202–2208.

    PubMed  CAS  Google Scholar 

  27. Caldwell JH, Revenaugh JI, Martin GV, Johnson PM, Rasey JS, Krohn KA. Comparison of fluorine-18-fluorodeoxy glucose and tritiated fluoromisonidazole uptake during low-flow ischemia. J Nucl Med 1995; 36: 1633–1638.

    PubMed  CAS  Google Scholar 

  28. Shelton ME, Dence CS, Hwang DR, Welch MJ, Bergmann SR. Myocardial kinetics of Fluorine-18 misonidazole: a marker of hypoxic myocardium. J Nucl Med 1989; 30: 351–358.

    PubMed  CAS  Google Scholar 

  29. Koh WJ, Bergman KS, Rasey JS, et al. Evaluation of oxygenation status during fractionated radiotherapy in human non small cell lung cancers using [F-18] fluoromisonidazole positron emission tomography. Int J Radiat Oncol Biol Phys 1995; 33: 391–398.

    Article  PubMed  CAS  Google Scholar 

  30. Koh WJ, Rasey JS, Evans ML, et al. Imaging of hypoxia in human tumors with [F-18] fluoromisonidazole. Int J Radiat Oncol Biol Phys 1991, 22: 199–212.

    Article  Google Scholar 

  31. Jette DC, Wiebe LI, Flanagan RJ, Lee J, Chapman, JD. Iodoazomycin riboside (1-(5′-iodo-5′-deoxyribofuranosyl)-2-nitroimidazole), a hypoxic cell marker. Radiat Res 1986; 105: 169–179.

    Article  PubMed  CAS  Google Scholar 

  32. Mannan RH, Mercer JR, Wiebe LI, Somayaji W, Chapman JD. Radioiodinated 1-(2-fluoro-4-iodo-2,4-dideoxy-(-1-xylopyranosyl)-2-nitroimidazole: a novel probe for the noninvasive assessment of tumor hypoxia. Radiat Res 1992; 132: 368–374.

    Article  PubMed  CAS  Google Scholar 

  33. Mannan RH, Somayaji W, Lee J, Mercer JR, Chapman JD, Wiebe LI. Radioiodinated 1-(5-iodo-5-deoxy-(-d-arabmofuranosyl)-2-nitroimidazole (iodoazomycin arabinoside: IAZA): a novel marker of tissue hypoxia. J Nucl Med 1991; 32: 1764–1770.

    PubMed  CAS  Google Scholar 

  34. Parliament MB, Chapman JD, Urtasun RC, et al. Non-invasive assesment of human tumour hypoxia with 1231-iodoazomycin arabinoside: preliminary report of a clinical study. Br J Cancer 1992; 65: 90–95.

    Article  PubMed  CAS  Google Scholar 

  35. Groshar D, McEwan AJB, Parliament MB, et al. Imaging tumor hypoxia and tumor perfusion. J Nucl Med 1993; 34: 885–888.

    PubMed  CAS  Google Scholar 

  36. Linder KE, Chan YW, Cyr JE, Nowotnik DP, Eckelman WC, Nunn AD. Synthesis, characterization, and in vitro evaluation of nitroimidazole-BATO complexes: new technetium compounds designed for imaging hypoxic tissue. Bioconjug Chem 1993; 4: 326–333.

    Article  PubMed  CAS  Google Scholar 

  37. Rumsey WL, Patel B, Linder KE. Effect of graded hypoxia on retention of technetium-99m-nitroheterocycle in perfused rat heart. J Nucl Med 1995; 36: 632–636.

    PubMed  CAS  Google Scholar 

  38. Ng CK, Sinusas AJ, Zaret BL, Soufer R. Kinetic analysis of technetium-99m-labeled nitroimidazole (BMS-181321) as a tracer of myocardial hypoxia. Circulation 1995; 92: 1261–1268.

    PubMed  CAS  Google Scholar 

  39. Stone CK, Mulnix T, Nickles RJ, et al. Myocardial kinetics of a putative hypoxic tissue marker 99mTc-labeled nitroimidazole (BMS-181321), after regional ischemia and reperfusion. Circulation 1995; 92: 1246–1253.

    PubMed  CAS  Google Scholar 

  40. Rumsey WL, Cyr JE, Raju N, Narra RK. A novel [99m]technetium-labeled nitroheterocycle capable of identification of hypoxia in heart. Biochem Biophys Res Comm 1993; 193: 1239–1246.

    Article  PubMed  CAS  Google Scholar 

  41. Rumsey WL, Kuczynski B, Patel B. Detecting hypoxia in heart using phosphorescence quenching and 99m-technetium-nitroimidazoles. In: Hogan MC, et al, editors. Oxygen transport to tissue XVI. New York: Plenum Press, 1994: 99–104.

    Google Scholar 

  42. Rumsey WL, Patel B, Kuczynski B, et al. Potential of nitroimidazoles as markers of hypoxia in heart. In: Vaupel P, et al, editors. Oxygen transport to tissue XV. New York: Plenum, 1994: 263–269.

    Google Scholar 

  43. Shi CQX, Sinusas AJ, Dione DP, et al. Technetium-99m-nitroimidazole (BMS 181321). a positive imaging agent for detecting myocardial ischemia. J Nucl Med 1995; 36: 1078–1086.

    PubMed  CAS  Google Scholar 

  44. Rumsey WL, Kuczynski B, Patel B, et al. SPECT imaging of ischemic myocardium using a technetium-99m-nitroimidazole ligand. J Nucl Med 1995; 36: 1445–1450.

    PubMed  CAS  Google Scholar 

  45. Wedeking P, Yost F, Wen M, et al. Comparison of the biologic activity of the isomers of the Tc-99m-nitroimidazole complex BMS-194796. J Nucl Med 1995; 36: 17P.

    Google Scholar 

  46. Archer CM, Edwards B, Kelly JD, King AC, Burke JF, Riley, ALM. Technetium labelled agents for imaging tissue hypoxia in vivo. In: Nicolini M, Bandoli G, Mazzi U, editors. Technetium and rhenium in chemistry and nuclear medicine 4. Padova: SG Editoriali, 1995: 535–539.

    Google Scholar 

  47. Johnson III G, Nguyen KN, Edwards B, Archer CM, Okada RD. HL91-technetium-99m: effects of flow and hypoxia on the myocardial kinetics of a new hypoxia avid imaging agent. Circulation 1995; 92 (Supplement 1): 3801.

    Google Scholar 

  48. Johnson III G, Nguyen KN, Edwards B, Archer CM, Okada RD. HL91-technetium-99m: uptake and retention of a new hypoxia avid imaging agent can differentiate ischemic viable from ischemic nonviable myocardium. Circulation 1995; 92 (Supplement 1): 3791.

    Google Scholar 

  49. Fujibayashi Y, Taniuchi H, Tajima N, Yonekura Y, Konishi J, Yokoyama A. New non nitroimidazole hypoxia imaging agents, Cu-62-dithiosemicarbazone complexes with low redox potential. J Nucl Med 1995; 36: 49P.

    Google Scholar 

  50. Fujibayashi Y, Wada K, Taniuchi H, Yonekura Y, Konishi J, Yokoyama A. Mitochondria-selective reduction of 62Cu-pyruvaldehyde bis(N4-methylthio-semicarbazone) (62Cu-PTSM) in the murine brain; a novel radiopharmaceutical for brain positron emission tomography (PET) imaging. Biol Pharm Bull 1993; 16: 146–149.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Colin M. Archer
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  2. Barbara Edwards
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  3. Nigel A. Powell
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Editor information

Editors and Affiliations

  1. Department of Nuclear Medicine, Imperial Cancer Research Fund, St. Bartholomew’s Hospital, London, EC1A 7BE, UK

    Stephen J. Mather

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© 1996 Kluwer Academic Publishers

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Archer, C.M., Edwards, B., Powell, N.A. (1996). Radiopharmaceuticals for Imaging Hypoxia. In: Mather, S.J. (eds) Current Directions in Radiopharmaceutical Research and Development. Developments in Nuclear Medicine, vol 30. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1768-2_5

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  • DOI: https://doi.org/10.1007/978-94-009-1768-2_5

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-7289-2

  • Online ISBN: 978-94-009-1768-2

  • eBook Packages: Springer Book Archive

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