Seminars in Nuclear Medicine
Volume 38, Issue 2 , Pages S19-S29 , March 2008

Use of the Oak Ridge National Laboratory Tungsten-188/Rhenium-188 Generator for Preparation of the Rhenium-188 HDD/Lipiodol Complex for Trans-Arterial Liver Cancer Therapy

  • Jae Min Jeong, PhD

      Affiliations

    • Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
  • ,
  • F.F.(Russ) Knapp Jr, PhD

      Affiliations

    • Nuclear Medicine Program, Nuclear Science and Technology Division, Oak Ridge National Laboratory (ORNL), Oak Ridge, TN.
    • Corresponding Author InformationAddress reprint requests to F. F. (Russ) Knapp, Jr, PhD, Nuclear Medicine Program, Nuclear Science and Technology Division, Oak Ridge National Laboratory (ORNL), PO Box 2008, Bethel Valley Road, Oak Ridge, TN 37831-6229.

References 

  1. Lambert B, de Klerk JMH. Clinical applications of 188Re-labelled radiopharmaceuticals for radionuclide therapy. Nucl Med Commun. 2006;27:223–230
  2. Knapp FF, Turner J, Padhy AK. Issues associated with the use of the Tungsten-188/Rhenium-188 generator and concentrator system and preparation of Re-188 HDD: A report. World J Nucl Med. 2004;3:137–143
  3. Jeong JM, Chung JK. Therapy with 188Re-labeled radiopharmaceuticals: An overview of promising results from initial clinical trials. Can Biother Radiopharm. 2003;18:707–717
  4. Knapp FF. Rhenium-188—a generator-derived radioisotope for cancer therapy. Can Biother Radiopharm. 1998;13:337–349
  5. Knapp FF, Lisic EJ, Mirzadeh S, et al. A new clinical prototype W-188/Re-188 generator to provide high levels of carrier-free Rhenium-188 for radioimmunotherapy. Eur J Nucl Med. 1991;18:538
  6. Knapp FF, Beets AL, Guhlke S, et al. Development of the alumina-based Tungsten-188/Rhenium-188 generator and use of Rhenium-188-labeled radiopharmaceuticals for cancer treatment. Antican Res. 1997;17:1783–1796
  7. Hambye AS, Dobbelier A, Vervaet AM, et al. Image quality with Rhenium-188 and technetium-99m: Comparative planar and SPECT evaluation in a phantom study and implications for dosimetry. World J Nucl Med. 2002;1:12–20
  8. Palmedo H, Manka-Waluch A, Albers P, et al. Repeated bone targeted therapy for hormone-refractory prostate carcinoma: Randomized phase II trial with the new, high-energy radiopharmaceutical Rhenium-188-HEDP. J Clin Oncol. 2003;21:2869–2875
  9. Liepe K, Kropp J, Hliscs R, et al. Radiation dosimetry of Rhenium-188-HEDP in human prostate cancer skeletal metastases. J Nucl Med. 2003;44:953–960
  10. Savio E, Gaudiano J, Robles A, et al. Rhenium-188-HEDP: Pharmacokinetic characterization in osseous metastatic patients with two levels of radiopharmaceutical dose. BMC Nucl Med. 2001;1:1471–1485
  11. Zhang H, Tian M, Li S, et al. Rhenium-188-HEDP therapy for the palliation of pain due to osseous metastases in lung cancer. Can Biother Radiopharm. 2003;18:719–726
  12. Blower PJ, Kettle AG, O’Doherty MJO, et al. 99mTc(V)-DMSA quantitatively predicts 188Re(V)DMSA distribution in patients with prostate cancer metastatic to bone. Eur J Nucl Med. 2000;27:1407–1409
  13. Blower PJ, Lam ASK, O’Doherty MJ, et al. Pentavalent Rhenium-188-dimercaptosuccinic acid for targeted radiotherapy: Synthesis and preliminary animal and human studies. Eur J Nucl Med. 1998;25:613–621
  14. Singh J, Reghebi K, Lazarus CR, et al. Studies on the preparation and isomeric composition of [186Re]- and [188Re]-pentavalent Rhenium dimercaptosuccinic acid complex. Nucl Med Commun. 1993;14:197–203
  15. Buchmann I, Bunjes D, Kotzerke J, et al. Myeloablative radioimmunotherapy with Re-188-anti-CD66-antibody for conditioning of high-risk leukemia patients prior to stem cell transplantation: Biodistribution, biokinetics and immediate toxicities. Cancer Biother Radiopharm. 2002;17:151–164
  16. Bunjes D, Buchmann I, Duncker C, et al. Rhenium-188-labeled anti-CD-66 (a,b,c,e) monoclonal antibody to intensify the conditioning regimen prior to stem cell transplantation for patients with high-Risk acute myeloid leukemia or myelodyspalstic syndrome: Results of phase I-II study. Blood. 2001;98:564–572
  17. Miao Y, Owen NK, Wittener D, et al. In vivo evaluation of 188Re-labeled alpha-melanocyte stimulating hormone peptide analogs for melanoma therapy. Int J Cancer. 2002;101:480–487
  18. Miao Y, Whitener D, Feng W, et al. Evaluation of the human melanoma targeting properties of radiolabeled α-melanocyte stimulating hormone peptide analogues. Bioconj Chem. 2003;14:1177–1184
  19. Bugaj JE, Bickel EM, Azure MT, et al. Radiotherapeutic efficacy of a SSTR-targeting peptide (188Re-P2045) in a small cell lung cancer (SCLC) mouse model. J Nucl Med. 2002;43:123P;(abstr)
  20. Lee EB, Shin KC, Lee Y-J, et al. 188Re-tin-colloid as a new therapeutic agent for rheumatoid arthritis. Nucl Med Commun. 2003;24:689–696
  21. Shin CY, Son M, Ko JI, et al. DA-7911, 188Re-tin-colloid, as a new therapeutic agent of rheumatoid arthritis. Arch Pharm Res. 2003;26:168–172
  22. Reynen K, Kropp J, Koeckeritz U, et al. Intracoronary radiotherapy with a Rhenium-188 liquid-filled angioplasty balloon system in in-stent restenosis: A single center, prospective, randomized, placebo-controlled, double-blind evaluation. Coron Artery Dis. 2006;17:371–377
  23. Hoher M, Wohrle J, Wohlfrom M, et al. Intracoronary beta-irradiation with Rhenium-188-filled balloon catheter: A randomized trial in patients with de novo and restenotic lesions. Circulation. 2003;107:3022–3027
  24. Kropp J, Reynen K, Koeckeritz U, et al. Prevention of in-stent stenosis with liquid filled 188Re balloon: the Dresden in-stent restenosis trial (DIRRT). World J Nucl Med. 2002;1(suppl 2):S13;(abstr)
  25. Park SW, Hong MK, Moon DH, et al. Treatment of diffuse in-stent restenosis with rotational atherectomy followed by radiation therapy with a Rhenium-188-mercaptoacetyltriglycine-filled balloon. J Am Coll Cardiol. 2001;38:631–637
  26. Knapp FF, Guhlke S, Beets AL, et al. Endovascular beta irradiation for prevention of restenosis using solution radioisotopes: Pharmacologic and dosimetric properties of Rhenium-188 compounds. Cardiovasc Rad Med. 1999;1:86–97
  27. Jeong JM, Kim YJ, Lee YS, et al. Lipiodol solution of a lipophilic agent, 188Re-TDD, for the treatment of liver cancer. Nucl Med Biol. 2001;28:197–204
  28. Kim YJ, Lee YS, Jeong JM, et al. Increased tissue uptake and retention of lipiodol solution of 188Re-N2S2 derivatives after introduction of long chain alkyl groups. J Nuc Med. 2001;42:116;(abstr)
  29. Sundram FX, Yu SW, Jeong JM, et al. 188Rhenium-TDD-lipiodol in treatment of inoperable primary hepatocellular carcinoma—A case report. Ann Acad Med Singapore. 2001;30:542–545
  30. Lee YS, Jeong JM, Kim YJ, et al. Synthesis of 188Re-labeled long chain alkyl diaminedithiol for therapy of liver cancer. Nucl Med Commun. 2002;23:237–242
  31. Boschi A, Uccelli L, Duatti A, et al. A kit formulation of the preparation of Re-188-lipiodol: Preclinical studies and preliminary therapeutic evaluation in patients with unresectable hepatocellular carcinoma. Nucl Med Commun. 2004;25:691–699
  32. Duatti A, Martindale AA, Turner JH, et al. Rhenium-188 lipiodol kit formulation for therapy of hepatocellular carcinoma (HCC). World J Nucl Med. 2002;1(suppl 2):S180;(abstr)
  33. Lee YS, Jeong JM, Kim YJ, et al. Development of acetylated HDD kit for preparation of 188Re-HDD/lipiodol. Appl Radiat Isot. 2007;65:64–69
  34. Kumar A, Bal C, Srivastava DN, et al. Management of multiple intrahepatic recurrences after radiofrequency ablation of hepatocellular carcinoma with Rhenium-188-HDD-lipiodol. Eur J Gastroenterol Hepatol. 2006;18:219–223
  35. Kumar A, Srivastava DN, Bal C. Management of postsurgical recurrence of hepatocellular carcinoma with Rhenium-188-HDD labeled iodized oil. J Vasc Interv Radiol. 2006;17:157–161
  36. Lambert B, Bacher K, Defreyne L, et al. 188Re-HDD/lipiodol therapy for hepatocellular carcinoma: An activity escalation study. Eur J Nucl Med. 2006;33:344–352
  37. Lambert B. Advantage of 188Re-radipharmaceuticals in heptacellular cancer and liver metastases, Reply to Letter to the Editor. J Nucl Med. 2005;46:1408
  38. Bernal P, Osorio M, Esguerra R, et al. Evaluation of Rhenium-188-lipiodol dosimetry in the treatment of liver cancer: Experience from Colombia. J Nucl Med. 2004;45:387P;(abstr)
  39. Bernal P, Osorio M, Guiterrez C, et al. Evaluation of Rhenium-188 lipiodol in the treatment of liver cancer: Experience in Colombia between 2001-2003. World J Nucl Med. 2004;3(suppl 1):S128;(abstr)
  40. Chau TTM. Some preliminary experiences on treatment of inoperable liver cancer with Re-188 HTDD lipiodol. World J Nucl Med. 2004;3(suppl 1):S128;(abstr)
  41. Chaudakshetrin P, Osorio M, Padhy AK, et al. Rhenium-188 lipiodol therapy of liver cancer: Optimization of conjugate view imaging of 188Re for patient-specific dosimetry. World J Nucl Med. 2004;3(suppl 1):S128;(abstr)
  42. De Ruyck K, Lambert B, Bacher K, et al. Biologic dosimetry of 188Re-HDD/lipiodol versus 131I-lipiodol therapy in patients with hepatocellular carcinoma. J Nucl Med. 2004;45:612–618
  43. Kumar A, Srivastava DN, Acharya SK, et al. Trans-hepatic-arterial Re-188 labeled lipiodol therapy (TART) in cases of inoperable hepatocellular carcinoma (IHCC): A prospective multicentric clinical trial. J Nucl Med. 2004;45:147P;(abstr)
  44. Onkhuudai P, Gonchigsuren D, Erdenechimeg S, et al. Trans-arterial radionuclide Re-188-lipiodol treatment of HCC. World J Nucl Med. 2004;3(suppl 1):S128;(abstr)
  45. Padhy AK. IAES initiatives in liver cancer. World J Nucl Med. 2004;3(suppl 1):S128;(abstr)
  46. Sundram F, Chaur TCM, Onkhuudai P, et al. Preliminary results of trans-arterial Rhenium-188 HDD lipiodol treatment of inoperable primary hepatocellular carcinoma. Eur J Nucl Med. 2004;31:250–257
  47. Sundram FX. Preliminary results of trans-arterial Rhenium-188 HDD-lipiodol in treatment of inoperable primary hepatocellular carcinoma. World J Nucl Med. 2004;3(suppl 1):S128;(abstr)
  48. Yoo CJ, Chung JW, Park JH, et al. Transcatheter arterial embolization with Rhenium-188-HDD-labeled iodized oil in rabbit VX2 liver tumor. J Vasc Interven Radiol. 2004;15:1121–1128
  49. Bernal P, Osorio M, Guiterrez C, et al. Evaluation of Rhenium-188 lipiodol in the treatment of liver cancer: Experience in Columbia. J Nucl Med. 2003;44:176P;(abstr)
  50. Chaudakshetrin P, Osorio M, Somanesan S, et al. Rhenium-188 lipiodol therapy of liver cancer: Optimization of conjugate-view imaging of Re-188 for patient-specific dosimetry. J Nucl Med. 2003;44:324P;(abstr)
  51. Paeng JC, Jeong JM, Chang CJ, et al. Lipiodol solution of 188Re-HDD as a new therapeutic agent for transhepatic arterial embolization in liver cancer: Preclinical study in a rabbit liver cancer model. J Nucl Med. 2003;44:2033–2038
  52. Keng GH, Sundram FX, Yu SW, et al. Preliminary experience in radionuclide therapy of hepatocellular carcinoma using hepatic-arterial radioconjugates. Ann Acad Med Singapore. 2002;31:382–386
  53. Zanzonico P, Divgi C, Sundram FX, et al. Maximum-tolerated activity treatment planning protocol for intrahepatic artery 188Re-lipiodol therapy of liver cancer. J Nucl Med. 2002;43:355P
  54. Bacher K, Thierens H, Van de Putte S, et al. 188Re-Lipiodol: Prediction of the patient dose based on 131I-lipiodol bi-planar scanning and Monte Carlo simulation. Eur J Nucl Med. 2001;28:1196
  55. Chung J-K, Kim YJ, Jeong JM, et al. Preparation of lipiodol solution of 188Re-4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HTDD) for treatment of liver cancer. Eur J Nucl Med. 2001;28:1228;(abstr)
  56. Jeong JM, Kim YJ, Lee Y-S, et al. Introduction of Long Alkyl Group Helps Uptake and Retention of Lipiodol Solution of 188Re-N2S2 Derivatives in the Tissues. J Lab Cmpds Radiopharm. 2001;44(suppl 1):S532–S533
  57. Sundram FX, Yu S, Somanesan S, et al. Phase I study of trans-arterial Rhenium-188-HDD lipiodol in treatment of inoperable primary hepatocellular carcinoma—a multicentre evaluation. World J Nucl Med. 2002;1:5–11
  58. Bernal P, Osorio M, Guiterrez C, et al. Evaluation of Rhenium-188 lipiodol In the treatment of liver cancer: Experience in Columbia. J Nuc Med. 2003;44:176P
  59. Wunderlich G, Drews A, Kotzerke J. A kit for labeling of [188Re] human serum albumin microspheres for therapeutic use in nuclear medicine. Appl Radiat Isot. 2005;62:915–918
  60. Wunderlich G, Pinkert J, Stintz M, et al. Labeling and bio-distribution of different particle materials for radioembolization therapy with 188Re. Appl Radiat Isot. 2005;62:745–750
  61. Kropp J, Pinkert J, Wunderlich G, et al. Radiochemistry, evaluation and first clinical results in the treatment of oncologic diseases with Rhenium-188-labeled microspheres. In: 2003;p. 157–166Proceedings, 11th Mediterranean Symposium on Nuclear Medicine and Radiopharmaceuticals, May 25-26, 2003, Athens, Greece, Mediterrea Pub
  62. Hafeli U, Pauer G, Failing S, et al. Radiolabeling of magnetic particles with Rhenium-188 for cancer therapy. J Magnetism Magnetic Mat. 2001;225:73–78
  63. Knapp FF. Rhenium-188-labeled radioactive particles and other radiopharmaceuticals for the treatment of liver cancer. Vienna, Austria: Internal IAEA publication; 2000;Proceedings, IAEA Workshop on Radionuclide Treatment of Liver Cancer, February 14-18, Singapore.
  64. Wunderlich G, Pinkert J, Franke W-G, et al. Preparation and biodistribution of Rhenium-188-labeled albumin microspheres: A promising new agent for endoradiotherapy of tumors. Appl Radiat Isot. 2000;52:63–68
  65. Garin E, Noire N, Malbert C, et al. Development and biodistribution of 188Re-SSS lipiodol following injection into the hepatic artery of healthy pigs. Eur J Nucl Med. 2004;31:542–546
  66. Garin E, Denizot B, Noiret N, et al. 188Re-SSS lipioldol: Radiolabeling and biodistribution following injection into the hepatic artery of rats bearing hepatoma. Nucl Med Commun. 2004;25:1007–1014
  67. Luo T-Y, Hsieh B-T, Wang S-J, et al. Preparation and biodistribution of Rhenium-188 ECD/lipiodol in rats following hepatic arterial injection. Nucl Med Biol. 2004;31:671–677
  68. Sun XG, Xiu Huang G. Comparative study of the therapeutic effect of intratumoral injection of Re-188-labeled stannic sulfur suspension and chemical agents for hepatoma in an animal model. J Nucl Med. 2004;45:296P
  69. Wang S-J, Lo T-Y, Hiseh B-T, et al. A new technique for labeling of lipiodol with 188Re in the treatment of hepatic tumor. J Radioanalyt Nucl Chem. 2004;261:189–193
  70. Oh SJ, Moon DH, Park SW, et al. A new automated system for routine preparation of 188Re-labeled radiopharmaceuticals. J Nucl Med. 2001;42:265P
  71. Jaeckel B, Cripps R, Guentay S, et al. Development of semi-automated system for preparation of 188Re aqueous solutions of high and reproducible activity concentrations. Appl Radiat Isot. 2005;63:299–304
  72. Guhlke S, Beets AL, Mirzadeh S, et al. Tandem cation/anion column treatment of ammonium acetate eluants of the alumina-based Tungsten-188/Rhenium-188 generator: A new simple method for effective concentration of Rhenium-188 perrhenate solutions. J Nucl Med. 2000;41:1271–1278
  73. Beets AL, Guhlke S, Biersack H-J, et al. Availability of very high radiopurity Rhenium-188 from a clinical-scale generator using a “Tandem” concentration system. Eur J Nucl Med. 1999;26:1010
  74. Knapp FF, Guhlke S, Beets AL, et al. Endovascular beta irradiation for prevention of restenosis using solution radioisotopes: Pharmacologic and dosimetric properties of Rhenium-188 compounds. Cardiovasc Rad Med. 1999;1:86–97
  75. Mushtaq A. Preparation of high specific volume solutions of technetium-99m and Rhenium-188. Appl Radiat Isot. 2003;58:309–314
  76. Iller E, Zekel Z, Konior M, et al. Technological line for production of carrier-free 188Re in the form of sterile, isotonic solution of sodium perrhenate (VII). In: Vienna, Austria: IAEA; 2005;p. 49–50Proceedings, International Symposium on Trends in Radiopharmaceuticals (ISTR) November 14-18, Vienna, Austria. (in press)
  77. Chen SL, Wang WD, Chen YC, et al. Generator elution and concentration of Rhenium-188. J Nucl Med. 2004;45:484P
  78. Mushtaq A. Concentration of 99mTcO4-/188ReO4 by a single, compact, anion-exchange cartridge. Nucl Med Commun. 2004;25:957–962

 Conflict of Interest: None.

PII: S0001-2998(07)00119-5

doi: 10.1053/j.semnuclmed.2007.10.003

Seminars in Nuclear Medicine
Volume 38, Issue 2 , Pages S19-S29 , March 2008