Clinical Development of Perfluorocarbon-based Emulsions as Red Cell Substitutes

  • Robert J. Kaufman


The use of PFCs in medicine has been the subject of much research over the past 30 years. Recent technological progress in second generation oxygen transport products has solved many of the problems of Fluosol DA® including PFC concentration, elimination of surfactant side effects and improved storage stability. Some side effects, most notably, thrombocytopenia and flu-like symptoms still remain to be solved. Two new oxygen transport formulations, Oxyfluor™ and Oxygent™ are in clinical trials at this time. Several applications of PFCs have been approved for use by the FDA but have languished in the market place. Prominent among these is the application of Fluosol DA® to PTCA and Imagent GI for MRI contrast in the bowel. Other applications such as cancer therapy, ultrasound contrast and direct19FMR imaging continue to show promise.


Oxygen Transport Functional Residual Capacity Ultrasound Contrast Agent Arterial Oxygen Tension Inspiratory Capacity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bajaj, A.K., M.A. Cobb, R. Virmani,et al.Limitation of myocardial reperfusion injury by intravenous perfluorochemicals.Circulation79: 645–656, 1989.PubMedCrossRefGoogle Scholar
  2. Behan, M., D.O. O’Connell, R.F. Mattrey, and D.N. Carney Perfluoroctyl bromide as a contrast agent for CT and sonography: preliminary clinical results.Am.J. Radiol.160: 399–405, 1993.Google Scholar
  3. Beppu, S., H. Matsuda, T. Shishido,et al.Success of myocardial contrast echocardiography by peripheral venous injection method: visualization of area at risk.Circulation88: 1-401 [abstract], 1993.Google Scholar
  4. Blauth, C.I., P.L. Smith, J.V. Arnold,et al.Influence of oxygenator type on the prevalence and extent of microembolic retinal ischemia during cardiopulmonary bypass.J. Thorac. Cardiovasc. Surg.99: 61–69, 1990.PubMedGoogle Scholar
  5. Brown, J. J., J.R. Duncan, J.P. Heiken,et al.Perfluorooctyl bromide as a gastrointestinal contrast agent for MR imaging: use with and without glucagon.Radiobiology181: 455–460, 1991.Google Scholar
  6. Bruneton, J.N., M.N. Falawese,et al.Liver, spleen and vessels: preliminary clinical results of CT with perfluorooctyl bromide.Radiology170: 179–183, 1989.PubMedGoogle Scholar
  7. Cernaianu, A.C., R.K. Spence, T. Vasilidze,et al. Transfusion triggers with perflubron (Oxygent) in a canine model of surgical hemodilution. InFifth International Symposium on Blood Substitutes: New Frontiers (T. Chang, J.G. Riess and R.M. Winslow, eds.)Google Scholar
  8. Clark, L.C., J. Ackerman, S. Thomas,et al.Perfluoiinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen.Adv. Exp. Med. Biol.180: 835–846, 1985.Google Scholar
  9. Clark, L.C., and F. Gollan. Survival of mammals breathing organic liquids equilibrated with oxygen at atmospheric pressure.Science152: 1755–1756, 1966.PubMedCrossRefGoogle Scholar
  10. Cleman, M., C.C. Jaffe, and D. Wholgelernter. Prevention of ischemia during percutaneous transluminal coronary angioplasty by transcatheter infusion of oxygenated Fluosol DA-20%.Circulation74: 555–562, 1986.PubMedCrossRefGoogle Scholar
  11. Cotter, B.O. L. Kwan, B. Kimura,et al.Evaluation of the efficacy, safety and pharmacokinetics of QW3600 (Echogen) in man.Circulation90: 1–555, 1994.Google Scholar
  12. Dardzinski, B.J., and C.H. Sotak. Rapid tissue oxygen tension mapping using 19F inversion recovery echo planar imaging of perfluoro-15-crown-5-ether.Mag. Reson. Med.32: 88–97, 1994.CrossRefGoogle Scholar
  13. DeMaria, A.N., H. Dittrich, O.L. Kwan,et al.Myocardial opacification produced by peripheral venous injection of a new ultrasonic contrast agent.Circulation88: 1-401 [abstract], 1993.Google Scholar
  14. Eidelberg, D., G. Johnson, D. Barnes,et al.19F NMR imaging of blood oxygenation in the brain.Mag. Reson. Med.6: 344–352, 1988.CrossRefGoogle Scholar
  15. Evans, R.G., B.F. Kimler, R.A. Morantz, and R.A. Batnitzky. Lack of complications in long-term survivors after treatment with Fluosol and oxygen as an adjuvant to radiation therapy for high-grade glioma.Int. J. Rad. Oncol. Bio. Phys.26: 649–652, 1989.CrossRefGoogle Scholar
  16. Flaim, S., D.R. Hazard, J. Hogan, and R.M. Peters. Characterization and mechanism of side-effects of Imagent BP (highly concentrated fluorocarbon emulsion) in swine.J. Invest. Radiol.26: S122–S124, 1991.Google Scholar
  17. Geyer, R.P., R.C. Monroe, and K. Taylor. Survival of rats totally perfused with a fluorocarbon-detergent preparation. InOrgan Perfusion and Preservation(J. Norman, ed.). New York: Appleton Century and Crofts, 1968, pp. 85–97.Google Scholar
  18. Glogar, D.H., R.A. Kloner, J. Muller,et al.Fluorocarbons reduce myocardial ischemic damage after coronary occlusion.Science211: 1439–1441, 1981.PubMedCrossRefGoogle Scholar
  19. Goodin, T.H., E.G. Grossbard, R.J. Kaufman,et al.A perfluorochemical emulsion for prehospital resuscitatien of experimental hemorrhagic shock: a prospective, randomized controlled study.Crit. Care Med.22: 680–689, 1994.PubMedCrossRefGoogle Scholar
  20. Gould, S.A, A.L. Rosen, L.R. Sehgal,et al.Fluosol DA as a red-cell substitute in acute anemia.N. Eng. J. Med.314: 1653–1656, 1986.CrossRefGoogle Scholar
  21. Greenspan, J.S., M.R. Wolfson, D. Rubenstein, and T.H. Shaffer. Liquid ventilation of human preterm neonatesJ. Pediatrics117: 106–111, 1990.CrossRefGoogle Scholar
  22. Gruber, M., M. Prados, C. Russell,et al.Phase I/II study of Fluosol and oxygen in combination® with BCNU in malignant glioma.Proc. Am. Assoc. Cancer Res.31: 190, 1990.Google Scholar
  23. Hopkins, R. Personal communication, 1994.Google Scholar
  24. Jaffe, C.C., D. Wohlgelernter, H. Cabin,et al.Preservation of left ventricular ejection fraction during percutaneous transluminal coronary angioplasty by distal transcatheter coronary perfusion of oxygenated Fluosol DA 20%.Am. Heart J.6: 1156–1164, 1988.CrossRefGoogle Scholar
  25. Joseph, P.M., Y. Yuasa, H.L. Kundel,et al.Magnetic resonance imaging of fluorine in rats infused with artificial blood.Invest. Radiol.20: 504–509, 1985PubMedCrossRefGoogle Scholar
  26. Kaufman, R.J. Medical oxygen transport using perfluorochemicals. In:Biotechnology of Blood (J. Goldstein, ed.). Boston: Butterworth-Heinemann, 1991, pp. 127–162.Google Scholar
  27. Kaufman, R.J. Perfluorochemical emulsions as blood substitutes. InEmulsions, a Fundamental and Practical Approach (J. Sjoblom, ed.). Boston: Kluwer Academic Publishers, 1992, pp. 207–226.Google Scholar
  28. Kaufman, R.J. The results of a Phase I clinical trial of a 40 v/v% emulsion of HM351 (Oxyfluor) in healthy human volunteers.Artif. Cells, Blood Substitutes, Immobil. Biotech.22: A112, 1994.Google Scholar
  29. Keipert, P. Use of Oxygent, a perfluorochemical (PFC) emulsion, as an antihypoxic agent to improve tissue oxygenation during acute blood loss. In:Blood Substitutes and Related Products: Advances in Development, Trial Design and Clinical Development( E. Scatchard and M. McBride, eds.) Southborough, MA: International Business Communications, 1994.Google Scholar
  30. Long, D.M., M.S. Liu, P.S. Szanto,et al.Efficacy and toxicity studies with radioopaque perfluorocarbon.Radiology133: 71, 1972a.Google Scholar
  31. Long, D.M., M.S. Liu, P.S. Szanto,et al.Forefront: preliminary communication–initial observations with a new x-ray contrast agent radioopaque perfluorocarbon.Rev. Surg.29: 71, 1972b.Google Scholar
  32. Long, D.M., F.K. Muiter, A.G. Greenburg,et al.Tumor imaging with x-rays using macrophage uptake of radioopaque fluorocarbon emulsions.Surgery84: 104–112, 1978.PubMedGoogle Scholar
  33. Longmaid, H., D. Adams,et al.In vivo 19F NMR imaging of liver, tumor and abcesses in rats.Invest. Radiol.20: 141–145, 1985.PubMedCrossRefGoogle Scholar
  34. Lustig, R., N. Mclntosh-Lowe, C. Rose,et al.Phase I/II study of Fluosol-DA and 100% oxygen as an adjuvant to radiation in the treatment of advanced squamous cell tumors of the head and neck.Int. J. Rad. Oncol. Biol. Phys.16: 1587–1593, 1989a.CrossRefGoogle Scholar
  35. Lustig, R., N. Lowe, L. Prosnitz,et al.Phase I/II study of Fluosol and 100% oxygen breathing as an adjuvant to radiation in the treatment of unresectable non-small cell carcinoma of the lung.Int. J. Rad. Oncol. Biol. Phys.17: 202, 1989b.CrossRefGoogle Scholar
  36. Mate, T.P., and S. Rockwell. Perfluorochemical emulsions do not affect bone marrow radiosensitivity. In:Abstracts, American Society Therapy Radiation Oncologists Meeting, Washington, D.C., Oct. 1984.Google Scholar
  37. Mattrey, R.F., F.W. Scheible, B.B. Gosink,et al.Perfluorooctyl bromide: a liver and spleen specific and a tumor imaging ultrasound contrast material.Radiology145: 759–762, 1982.PubMedGoogle Scholar
  38. Mattrey, R.F., G.R. Leopold, E. vanSonneberg,et al.Perfluorochemicals as a liver and spleen seeking ultrasound contrast agent.J. Ultrasound Med.2: 173–176, 1983.PubMedGoogle Scholar
  39. Mattrey, R.F., D.M. Long, R.A. Slutsky, and G.B. Higgins. Perfluorooctyl bromide as a blood pool contrast agent for liver, spleen and vascular imaging.J. Comput. Assist. Tombgr.8: 739–744, 1984.CrossRefGoogle Scholar
  40. Mattrey, R.F., G. Strich, R.E. Shelton,et al.Perfluorochemicals as ultrasound contrast agents for tumor imaging and hepatosplenography: preliminary clinical results.Radiology163: 339–343, 1987.PubMedGoogle Scholar
  41. Mattrey R.F., M.A. Trammert, J.J. Brown,et al.Oral contrast agents for magnetic resonance imaging.Invest. Radiol.26: S65–S66, 1991.PubMedCrossRefGoogle Scholar
  42. Modell, J.H., E.J. Newby, and B.C. Ruiz. Long-term survival of dogs after breathing oxygenated fluorocarbon liquid.Fed. Proc.34: 312–320, 1970.Google Scholar
  43. Modell, J.H., H.W. Calderwood, B.C. Ruiz,et al.Liquid ventilation of primates.Chest69: 79–81, 1976.PubMedCrossRefGoogle Scholar
  44. Moody, D.M., M.A. Bell, V.R. Challa,et al.Brain microemboli during cardiac surgery or aortography.Annu. Neurol .28: 477–486, 1990.CrossRefGoogle Scholar
  45. Nunn, G.R., G. Dance, J. Peters, and L.H. Cohn. Effect of fluorocarbon exchange transfusion on myocardial infarction in dogs.Am. J. Cardiol.52: 203–205, 1983.PubMedCrossRefGoogle Scholar
  46. Riess, J.G., and M. Leblanc. Perfluoro compounds as blood substitutes.Angewande Chemie International Edition in English17: 621–634, 1978.CrossRefGoogle Scholar
  47. Riess, J.G. Reassessment of the criteria for the selection of perfluorochemicals for second generation blood substitutes: analysis of structure-property relationships.Artif. Organs8: 44–56, 1984.PubMedCrossRefGoogle Scholar
  48. Rose, CM., R. Lustig, N. Mcintosh, and BA. Teicher. A clinical trial of Fluosol DA 20% in advanced squamous cell carcinoma of the head and neck.Int. J. Rad. Oncol. Biol. Phys.12: 1325–1327, 1986.CrossRefGoogle Scholar
  49. Schweighardt, F.K., and D. Woo. Interstitial administration of perfluorochemical emulsions for reoxygenation of hypoxic tumor cells.US Patent No. 4, 781, 676, 1988.Google Scholar
  50. Schweighardt, F.K. Perfluoro-crown ethers in fluorine magnetic resonance imaging.US PatentNo. 4,838, 274, 1989.Google Scholar
  51. Shaffer, T.H., and G.D. Moskowitz. Demand-controlled liquid ventilation of the lungs,J. Appi. Physiol.36: 208–213, 1974.Google Scholar
  52. Shaw P.J., D. Bates, N.E. Cartlidge,et al.Neurologic and neuropsychological morbidity following major surgery: comparison of coronary bypass and peripheral vascular surgery.Stroke18: 700–707, 1987.PubMedCrossRefGoogle Scholar
  53. Sloviter, H., and T. Kamimoto. Erythrocyte substitute for perfusion of brain.Nature216: 458, 1967.PubMedCrossRefGoogle Scholar
  54. Song, C.W., I. Lee, T. Kasegawa,et al.Increase in PO2 and radiosensitivity of tumors by Fluosol-DA(20%).Cancer Res. 47: 442–446, 1987.PubMedGoogle Scholar
  55. Spears, R., J. Serur, D. Baim,et. al. Myocardial protection with Fluosol-DA during prolonged coronary balloon occlusion in the dog.Circulation 73:II -245 [abstract], 1983.Google Scholar
  56. Spence, R.K. Use of Oxygent, perfluorocarbons in the twenty-first century: clinical applications as transfusion alternatives. InBlood Substitutes and Related Products (E. Scatchard and M. McBride, eds.) Southborough, MA: International Business Communications, 1994.Google Scholar
  57. Spiess, B.D., R.J. McCarthy, K.J. Turnan, A.W. Woronowicz, EA Tool, and A.D. Ivanovich. Treatment of decompression sickness with a perfluorocarbon emulsion (FC-43).Undersea Biomed. Res.15: 31–37, 1988.PubMedGoogle Scholar
  58. Taylor, K.M., J.V. Arnold, J. Fleming, A.C. Bird, E.G. Grossbard, and R.J. Kaufman. Cerebral protection during CPB using perfluorocarbon: a preliminary report. InSecond International Conference on the Brain and Cardiac Surgery. Key West FL [abstract], 1992.Google Scholar
  59. Teicher, B.A., and S. Rockwell. Increased efficacy of radiotherapy in mice treated with perfluorochemical emulsions plus oxygen.Am. Assoc. of Cancer Res. Abstract 25–28, 1983.Google Scholar
  60. Teicher, B.A., S.A. Holden, G. Ara,et al.A new concentrated perfluorochemical emulsion and carbogen breathing as a adjuvant to treatment with antitumor alkylating agents.J. Cancer Res. Clin. Oncol.118: 509–514, 1992.PubMedCrossRefGoogle Scholar
  61. Tremper, K.K., G.M. Vercellotti, and D.E. Hammerschmidt. Hemodynamic profile of adverse clinical reactions to Fluosol DA 20%.Crit. Care Med.12: 428–431, 1984.PubMedCrossRefGoogle Scholar
  62. Wall, T.C., R.M. Califf, J. Blamkenship,et al.Intravenous Fluosol in the treatment of acute myocardial infarction.Circulation90: 114–126, 1994.PubMedGoogle Scholar

Copyright information

© Birkhäuser Boston 1995

Authors and Affiliations

  • Robert J. Kaufman
    • 1
  1. 1.HemaGen / PFCSt. LouisUSA

Personalised recommendations