Kidney protection during peptide receptor radionuclide therapy with somatostatin analogues

  • Edgar J. Rolleman
  • Marleen Melis
  • Roelf Valkema
  • Otto C. Boerman
  • Eric P. Krenning
  • Marion de Jong
Review Article


This review focuses on the present status of kidney protection during peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues. This treatment modality for somatostatin receptor-positive tumours is limited by renal reabsorption and retention of radiolabelled peptides resulting in dose-limiting high kidney radiation doses. Radiation nephropathy has been described in several patients. Studies on the mechanism and localization demonstrate that renal uptake of radiolabelled somatostatin analogues largely depends on the megalin/cubulin system in the proximal tubule cells. Thus methods are needed that interfere with this reabsorption pathway to achieve kidney protection. Such methods include coadministration of basic amino acids, the bovine gelatin-containing solution Gelofusine or albumin fragments. Amino acids are already commonly used in the clinical setting during PRRT. Other compounds that interfere with renal reabsorption capacity (maleic acid and colchicine) are not suitable for clinical use because of potential toxicity. The safe limit for the renal radiation dose during PRRT is not exactly known. Dosimetry studies applying the principle of the biological equivalent dose (correcting for the effect of dose fractionation) suggest that a dose of about 37 Gy is the threshold for development of kidney toxicity. This threshold is lower when risk factors for development of renal damage exist: age over 60 years, hypertension, diabetes mellitus and previous chemotherapy. A still experimental pathway for kidney protection is mitigation of radiation effects, possibly achievable by cotreatment with amifostine (Ethylol), a radiation protector, or with blockers of the renin-angiotensin-aldosterone system. Future perspectives on improving kidney protection during PRRT include combinations of agents to reduce renal retention of radiolabelled peptides, eventually together with mitigating medicines. Moreover, new somatostatin analogues with lower renal retention may be developed. Furthermore, knowledge on kidney protection from radiolabelled somatostatin analogues may be expanded to other peptides.


Kidney protection Peptide receptor radionuclide therapy Somatostatin analogues Somatostatin receptor-positive tumours 


  1. 1.
    Krenning EP, Bakker WH, Breeman WA, Koper JW, Kooij PP, Ausema L, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989;1:242–4.PubMedGoogle Scholar
  2. 2.
    Reubi JC, Krenning E, Lamberts SW, Kvols L. In vitro detection of somatostatin receptors in human tumors. Digestion 1993;54:76–83.PubMedGoogle Scholar
  3. 3.
    Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al. Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000;27:273–82.PubMedGoogle Scholar
  4. 4.
    Hofland LJ, van Koetsveld PM, Waaijers M, Lamberts SW. Internalisation of isotope-coupled somatostatin analogues. Digestion 1996;57(Suppl 1):2–6.PubMedGoogle Scholar
  5. 5.
    De Jong M, Bernard BF, De Bruin E, Van Gameren A, Bakker WH, Visser TJ, et al. Internalization of radiolabelled [DTPA0]octreotide and [DOTA0,Tyr3]octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy. Nucl Med Commun 1998;19:283–8.PubMedGoogle Scholar
  6. 6.
    Andersson P, Forssell-Aronsson E, Johanson V, Wangberg B, Nilsson O, Fjalling M, et al. Internalization of indium-111 into human neuroendocrine tumor cells after incubation with indium-111-DTPA-D-Phe1-octreotide. J Nucl Med 1996;37:2002–6.PubMedGoogle Scholar
  7. 7.
    Duncan JR, Stephenson MT, Wu HP, Anderson CJ. Indium-111-diethylenetriaminepentaacetic acid-octreotide is delivered in vivo to pancreatic, tumor cell, renal, and hepatocyte lysosomes. Cancer Res 1997;57:659–71.PubMedGoogle Scholar
  8. 8.
    Krenning EP, Kooij PP, Bakker WH, Breeman WA, Postema PT, Kwekkeboom DJ, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D-Phe1]-octreotide. A case history. Ann N Y Acad Sci 1994;733:496–506.PubMedGoogle Scholar
  9. 9.
    Valkema R, De Jong M, Bakker WH, Breeman WA, Kooij PP, Lugtenburg PJ, et al. Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience. Semin Nucl Med 2002;32:110–22.PubMedGoogle Scholar
  10. 10.
    Anthony LB, Woltering EA, Espenan GD, Cronin MD, Maloney TJ, McCarthy KE. Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med 2002;32:123–32.PubMedGoogle Scholar
  11. 11.
    Buscombe JR, Caplin ME, Hilson AJ. Long-term efficacy of high-activity 111In-pentetreotide therapy in patients with disseminated neuroendocrine tumors. J Nucl Med 2003;44:1–6.PubMedGoogle Scholar
  12. 12.
    Waldherr C, Pless M, Maecke HR, Schumacher T, Crazzolara A, Nitzsche EU, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med 2002;43:610–6.PubMedGoogle Scholar
  13. 13.
    Valkema R, Pauwels S, Kvols LK, Barone R, Jamar F, Bakker WH, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0,Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 2006;36:147–56.PubMedGoogle Scholar
  14. 14.
    Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, et al. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 1999;26:1439–47.PubMedGoogle Scholar
  15. 15.
    Bodei L, Cremonesi M, Zoboli S, Grana C, Bartolomei M, Rocca P, et al. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging 2003;30:207–16.PubMedGoogle Scholar
  16. 16.
    Bushnell D, O'Dorisio T, Menda Y, Carlisle T, Zehr P, Connolly M, et al. Evaluating the clinical effectiveness of 90Y-SMT 487 in patients with neuroendocrine tumors. J Nucl Med 2003;44:1556–60.PubMedGoogle Scholar
  17. 17.
    Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med 2005;46:62S–6S.PubMedGoogle Scholar
  18. 18.
    Teunissen JJ, Kwekkeboom DJ, Krenning EP. Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Clin Oncol 2004;22:2724–9.PubMedGoogle Scholar
  19. 19.
    Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, et al. Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide. Eur J Nucl Med 2001;28:426–34.PubMedGoogle Scholar
  20. 20.
    Paganelli G, Zoboli S, Cremonesi M, Macke HR, Chinol M. Receptor-mediated radionuclide therapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide: preliminary report in cancer patients. Cancer Biother Radiopharm 1999;14:477–83.PubMedGoogle Scholar
  21. 21.
    Cybulla M, Weiner SM, Otte A. End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med 2001;28:1552–4.PubMedGoogle Scholar
  22. 22.
    Stoffel MP, Pollok M, Fries J, Baldamus CA. Radiation nephropathy after radiotherapy in metastatic medullary thyroid carcinoma. Nephrol Dial Transplant 2001;16:1082–3.PubMedGoogle Scholar
  23. 23.
    Moll S, Nickeleit V, Mueller-Brand J, Brunner FP, Maecke HR, Mihatsch MJ. A new cause of renal thrombotic microangiopathy: yttrium 90-DOTATOC internal radiotherapy. Am J Kidney Dis 2001;37:847–51.PubMedGoogle Scholar
  24. 24.
    Barone R, Borson-Chazot F, Valkema R, Walrand S, Chauvin F, Gogou L, et al. Patient-specific dosimetry in predicting renal toxicity with 90Y-DOTATOC: relevance of kidney volume and dose rate in finding a dose-effect relationship. J Nucl Med 2005;46:99S–106S.PubMedGoogle Scholar
  25. 25.
    Lewis JS, Wang M, Laforest R, Wang F, Erion JL, Bugaj JE, et al. Toxicity and dosimetry of (177)Lu-DOTA-Y3-octreotate in a rat model. Int J Cancer 2001;94:873–7.PubMedGoogle Scholar
  26. 26.
    Rolleman EJ, Krenning EP, Bernard BF, de Visser M, Bijster M, Visser TJ, et al. Long-term toxicity of [(177)Lu-DOTA(0),Tyr(3)]octreotate in rats. Eur J Nucl Med Mol Imaging 2007;34:219–27.PubMedGoogle Scholar
  27. 27.
    Jaggi JS, Seshan SV, McDevitt MR, LaPerle K, Sgouros G, Scheinberg DA. Renal tubulointerstitial changes after internal irradiation with alpha-particle-emitting actinium daughters. J Am Soc Nephrol 2005;16:2677–89.PubMedGoogle Scholar
  28. 28.
    Konijnenberg M, Melis M, Valkema R, Krenning E, de Jong M. Radiation dose distribution in human kidneys by octreotides in peptide receptor radionuclide therapy. J Nucl Med 2007;48:134–42.PubMedGoogle Scholar
  29. 29.
    Maack T, Johnson V, Kau ST, Figueiredo J, Sigulem D. Renal filtration, transport, and metabolism of low-molecular-weight proteins: a review. Kidney Int 1979;16:251–70.PubMedGoogle Scholar
  30. 30.
    Maack T, Park CH. Endocytosis and lysosomal hydrolysis of proteins in proximal tubules. Methods Enzymol 1990;191:340–54.PubMedGoogle Scholar
  31. 31.
    Melis M, Krenning EP, Bernard BF, Barone R, Visser TJ, de Jong M. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues. Eur J Nucl Med Mol Imaging 2005;32:1136–43.PubMedGoogle Scholar
  32. 32.
    De Jong M, Valkema R, Van Gameren A, Van Boven H, Bex A, Van De Weyer EP, et al. Inhomogeneous localization of radioactivity in the human kidney after injection of [(111)In-DTPA]octreotide. J Nucl Med 2004;45:1168–71.PubMedGoogle Scholar
  33. 33.
    Barone R, Van Der Smissen P, Devuyst O, Beaujean V, Pauwels S, Courtoy PJ, et al. Endocytosis of the somatostatin analogue, octreotide, by the proximal tubule-derived opossum kidney (OK) cell line. Kidney Int 2005;67:969–76.PubMedGoogle Scholar
  34. 34.
    De Jong M, Barone R, Krenning E, Bernard B, Melis M, Visser T, et al. Megalin is essential for renal proximal tubule reabsorption of 111In-DTPA-octreotide. J Nucl Med 2005;46:1696–700.PubMedGoogle Scholar
  35. 35.
    Balster DA, O'Dorisio MS, Summers MA, Turman MA. Segmental expression of somatostatin receptor subtypes sst(1) and sst(2) in tubules and glomeruli of human kidney. Am J Physiol Renal Physiol 2001;280:F457–65.PubMedGoogle Scholar
  36. 36.
    Reubi JC, Horisberger U, Studer UE, Waser B, Laissue JA. Human kidney as target for somatostatin: high affinity receptors in tubules and vasa recta. J Clin Endocrinol Metab 1993;77:1323–8.PubMedGoogle Scholar
  37. 37.
    Rolleman EJ, Kooij PP, de Herder WW, Valkema R, Krenning EP, de Jong M. Somatostatin receptor subtype 2-mediated uptake of radiolabelled somatostatin analogues in the human kidney. Eur J Nucl Med Mol Imaging 2007;34:1854–60.PubMedGoogle Scholar
  38. 38.
    Stahl AR, Wagner B, Poethko T, Perutka M, Wester HJ, Essler M, et al. Renal accumulation of [111In]DOTATOC in rats: influence of inhibitors of the organic ion transport and diuretics. Eur J Nucl Med Mol Imaging 2007;34:2129–34.PubMedGoogle Scholar
  39. 39.
    Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109–22.PubMedGoogle Scholar
  40. 40.
    Boerman OC, Oyen WJ, Corstens FH. Between the Scylla and Charybdis of peptide radionuclide therapy: hitting the tumor and saving the kidney. Eur J Nucl Med 2001;28:1447–9.PubMedGoogle Scholar
  41. 41.
    O'Donoghue J. Relevance of external beam dose-response relationships to kidney toxicity associated with radionuclide therapy. Cancer Biother Radiopharm 2004;19:378–87.PubMedGoogle Scholar
  42. 42.
    Konijnenberg MW. Is the renal dosimetry for [90Y-DOTA0,Tyr3]octreotide accurate enough to predict thresholds for individual patients? Cancer Biother Radiopharm 2003;18:619–25.PubMedGoogle Scholar
  43. 43.
    Pauwels S, Barone R, Walrand S, Borson-Chazot F, Valkema R, Kvols LK, et al. Practical dosimetry of peptide receptor radionuclide therapy with 90Y-labeled somatostatin analogs. J Nucl Med 2005;46:92S–8S.PubMedGoogle Scholar
  44. 44.
    Forster GJ, Engelbach MJ, Brockmann JJ, Reber HJ, Buchholz HG, Macke HR, et al. Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumours: comparison of (86)Y-DOTATOC and (111)In-DTPA-octreotide. Eur J Nucl Med 2001;28:1743–50.PubMedGoogle Scholar
  45. 45.
    Cremonesi M, Ferrari M, Bodei L, Tosi G, Paganelli G. Dosimetry in peptide radionuclide receptor therapy: a review. J Nucl Med 2006;47:1467–75.PubMedGoogle Scholar
  46. 46.
    Wehrmann C, Senftleben S, Zachert C, Muller D, Baum RP. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm 2007;22:406–16.PubMedGoogle Scholar
  47. 47.
    Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. 86Y-DOTA(0)-d-Phe(1)-Tyr(3)-octreotide (SMT487) – a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging 2003;30:510–8.PubMedGoogle Scholar
  48. 48.
    Cremonesi M, Ferrari M, Zoboli S, Chinol M, Stabin MG, Orsi F, et al. Biokinetics and dosimetry in patients administered with (111)In-DOTA-Tyr(3)-octreotide: implications for internal radiotherapy with (90)Y-DOTATOC. Eur J Nucl Med 1999;26:877–86.PubMedGoogle Scholar
  49. 49.
    Stahl A, Schachoff S, Beer A, Winter A, Wester HJ, Scheidhauer K, et al. [(111)In]DOTATOC as a dosimetric substitute for kidney dosimetry during [(90)Y]DOTATOC therapy: results and evaluation of a combined gamma camera/probe approach. Eur J Nucl Med Mol Imaging 2006;33:1328–36.PubMedGoogle Scholar
  50. 50.
    Forrer F, Uusijarvi H, Waldherr C, Cremonesi M, Bernhardt P, Mueller-Brand J, et al. A comparison of (111)In-DOTATOC and (111)In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004;31:1257–62.PubMedGoogle Scholar
  51. 51.
    Barone R, Jamar F, Walrand S, Labar D, Carlier P, Smith C, et al. Can 111In-DTPA-octreotide (In-OC) predict kidney and tumor exposure during treatment with 90Y SMT487 (OctreoTher TM)? J Nucl Med 2000;41:110P.Google Scholar
  52. 52.
    Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007;48:508–18.PubMedGoogle Scholar
  53. 53.
    Buchmann I, Henze M, Engelbrecht S, Eisenhut M, Runz A, Schafer M, et al. Comparison of 68Ga-DOTATOC PET and 111In-DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2007;34:1617–26.PubMedGoogle Scholar
  54. 54.
    Prasad V, Ambrosini V, Hommann M, Hoersch D, Fanti S, Baum RP. Detection of unknown primary neuroendocrine tumours (CUP-NET) using (68)Ga-DOTA-NOC receptor PET/CT. Eur J Nucl Med Mol Imaging 2009. doi: 10.1007/s00259-009-1205-y
  55. 55.
    Fanti S, Ambrosini V, Tomassetti P, Castellucci P, Montini G, Allegri V, et al. Evaluation of unusual neuroendocrine tumours by means of 68Ga-DOTA-NOC PET. Biomed Pharmacother 2008;62:667–71.PubMedGoogle Scholar
  56. 56.
    Prasad V, Baum RP. Biodistribution of the Ga-68 labeled pansomatostatin analog DOTA-NOC: uptake in normal organs, in neuroendocrine primary tumors and in metastases. J Nucl Med 2007;48 (Suppl 2):373P.Google Scholar
  57. 57.
    Baum RP, Prasad V, Hommann M, Horsch D. Receptor PET/CT imaging of neuroendocrine tumors. Recent Results Cancer Res 2008;170:225–42.PubMedGoogle Scholar
  58. 58.
    Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, et al. Comparison of [(177)Lu-DOTA(0),Tyr (3)]octreotate and [(177)Lu-DOTA (0),Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging 2006;33:1346–51.PubMedGoogle Scholar
  59. 59.
    Konijnenberg MW, Bijster M, Krenning EP, De Jong M. A stylized computational model of the rat for organ dosimetry in support of preclinical evaluations of peptide receptor radionuclide therapy with (90)Y, (111)In, or (177)Lu. J Nucl Med 2004;45:1260–9.PubMedGoogle Scholar
  60. 60.
    Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124–30.PubMedGoogle Scholar
  61. 61.
    Valkema R, Pauwels SA, Kvols LK, Kwekkeboom DJ, Jamar F, de Jong M, et al. Long-term follow-up of renal function after peptide receptor radiation therapy with 90Y-DOTA0,Tyr3-octreotide and 177Lu-DOTA0,Tyr3-octreotate. J Nucl Med 2005;46:83S–91S.PubMedGoogle Scholar
  62. 62.
    Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008;35:1847–56.PubMedGoogle Scholar
  63. 63.
    Forrer F, Uusijarvi H, Storch D, Maecke HR, Mueller-Brand J. Treatment with 177Lu-DOTATOC of patients with relapse of neuroendocrine tumors after treatment with 90Y-DOTATOC. J Nucl Med 2005;46:1310–6.PubMedGoogle Scholar
  64. 64.
    Stewart FA, Lebesque JV, Hart AA. Progressive development of radiation damage in mouse kidneys and the consequences for reirradiation tolerance. Int J Radiat Biol Relat Stud Phys Chem Med 1988;53:405–15.PubMedGoogle Scholar
  65. 65.
    Stewart FA, Oussoren Y, Luts A, Begg AC, Dewit L, Lebesque J, et al. Repair of sublethal radiation injury after multiple small doses in mouse kidney: an estimate of flexure dose. Int J Radiat Oncol Biol Phys 1987;13:765–72.PubMedGoogle Scholar
  66. 66.
    Cohen EP, Robbins ME. Radiation nephropathy. Semin Nephrol 2003;23:486–99.PubMedGoogle Scholar
  67. 67.
    Behr TM, Goldenberg DM, Becker W. Reducing the renal uptake of radiolabeled antibody fragments and peptides for diagnosis and therapy: present status, future prospects and limitations. Eur J Nucl Med 1998;25:201–12.PubMedGoogle Scholar
  68. 68.
    Mogensen CE, Solling. Studies on renal tubular protein reabsorption: partial and near complete inhibition by certain amino acids. Scand J Clin Lab Invest 1977; 37:477–86.PubMedGoogle Scholar
  69. 69.
    Hammond PJ, Wade AF, Gwilliam ME, Peters AM, Myers MJ, Gilbey SG, et al. Amino acid infusion blocks renal tubular uptake of an indium-labelled somatostatin analogue. Br J Cancer 1993;67:1437–9.PubMedGoogle Scholar
  70. 70.
    Behr TM, Sharkey RM, Juweid ME, Blumenthal RD, Dunn RM, Griffiths GL, et al. Reduction of the renal uptake of radiolabeled monoclonal antibody fragments by cationic amino acids and their derivatives. Cancer Res 1995;55:3825–34.PubMedGoogle Scholar
  71. 71.
    De Jong M, Rolleman EJ, Bernard BF, Visser TJ, Bakker WH, Breeman WA, et al. Inhibition of renal uptake of indium-111-DTPA-octreotide in vivo. J Nucl Med 1996;37:1388–92.PubMedGoogle Scholar
  72. 72.
    Bernard BF, Krenning EP, Breeman WA, Rolleman EJ, Bakker WH, Visser TJ, et al. D-lysine reduction of indium-111 octreotide and yttrium-90 octreotide renal uptake. J Nucl Med 1997;38:1929–33.PubMedGoogle Scholar
  73. 73.
    Rolleman EJ, Valkema R, De Jong M, Kooij PP, Krenning EP. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med Mol Imaging 2003;30:9–15.PubMedGoogle Scholar
  74. 74.
    Sartori S, Nielsen I, Pennacchio G, Pazzi P, Pazzi L. Hyperkalaemia during infusion of hyperosmolar amino acid solutions enriched with branched chain amino acids. Report of two cases. Recenti Prog Med 1991;82:275–7.PubMedGoogle Scholar
  75. 75.
    Massara F, Cagliero E, Bisbocci D, Passarino G, Carta Q, Molinatti GM. The risk of pronounced hyperkalaemia after arginine infusion in the diabetic subject. Diabete Metab 1981;7:149–53.PubMedGoogle Scholar
  76. 76.
    Massara F, Martelli S, Ghigo E, Camanni F, Molinatti GM. Arginine-induced hypophosphatemia and hyperkaliemia in man. Diabete Metab 1979;5:297–300.PubMedGoogle Scholar
  77. 77.
    Bushinsky DA, Gennari FJ. Life-threatening hyperkalemia induced by arginine. Ann Intern Med 1978;89:632–4.PubMedGoogle Scholar
  78. 78.
    Perazella MA, Biswas P. Acute hyperkalemia associated with intravenous epsilon-aminocaproic acid therapy. Am J Kidney Dis 1999;33:782–5.PubMedGoogle Scholar
  79. 79.
    Barone R, De Camps J, Smith C, Kvols L, Krenning EP, Pauwels S, et al. Metabolic effect of amino acids (AA) solutions infused for renal radioprotection. J Nucl Med 2000;41:94P.Google Scholar
  80. 80.
    Chinol M, Bodei L, Cremonesi M, Paganelli G. Receptor-mediated radiotherapy with Y-DOTA-DPhe-Tyr-octreotide: the experience of the European Institute of Oncology Group. Semin Nucl Med 2002;32:141–7.PubMedGoogle Scholar
  81. 81.
    Racusen LC, Whelton A, Solez K. Effects of lysine and other amino acids on kidney structure and function in the rat. Am J Pathol 1985;120:436–42.PubMedGoogle Scholar
  82. 82.
    Racusen LC, Finn WF, Whelton A, Solez K. Mechanisms of lysine-induced acute renal failure in rats. Kidney Int 1985;27:517–22.PubMedGoogle Scholar
  83. 83.
    Malis CD, Racusen LC, Solez K, Whelton A. Nephrotoxicity of lysine and of a single dose of aminoglycoside in rats given lysine. J Lab Clin Med 1984;103:660–76.PubMedGoogle Scholar
  84. 84.
    Abel RM, Beck CH Jr, Abbott WM, Ryan JA Jr, Barnett GO, Fischer JE. Improved survival from acute renal failure after treatment with intravenous essential L-amino acids and glucose. Results of a prospective, double-blind study. N Engl J Med 1973;288:695–9.PubMedCrossRefGoogle Scholar
  85. 85.
    van Eerd JE, Vegt E, Wetzels JF, Russel FG, Masereeuw R, Corstens FH, et al. Gelatin-based plasma expander effectively reduces renal uptake of 111In-octreotide in mice and rats. J Nucl Med 2006;47:528–33.PubMedGoogle Scholar
  86. 86.
    Veldman BA, Schepkens HL, Vervoort G, Klasen I, Wetzels JF. Low concentrations of intravenous polygelines promote low-molecular weight proteinuria. Eur J Clin Invest 2003;33:962–8.PubMedGoogle Scholar
  87. 87.
    ten Dam MA, Branten AJ, Klasen IS, Wetzels JF. The gelatin-derived plasma substitute gelofusine causes low-molecular-weight proteinuria by decreasing tubular protein reabsorption. J Crit Care 2001;16:115–20.PubMedGoogle Scholar
  88. 88.
    Vegt E, Wetzels JF, Russel FG, Masereeuw R, Boerman OC, van Eerd JE, et al. Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin. J Nucl Med 2006;47:432–36.PubMedGoogle Scholar
  89. 89.
    Rolleman EJ, Bernard BF, Breeman WA, Forrer F, de Blois E, Hoppin J, et al. Molecular imaging of reduced renal uptake of radiolabelled [DOTA0,Tyr3]octreotate by the combination of lysine and gelofusine in rats. Nuklearmedizin 2008;47:110–5.PubMedGoogle Scholar
  90. 90.
    Gotthardt M, van Eerd-Vismale J, Oyen WJ, de Jong M, Zhang H, Rolleman E, et al. Indication for different mechanisms of kidney uptake of radiolabeled peptides. J Nucl Med 2007;48:596–601.PubMedGoogle Scholar
  91. 91.
    Barron ME, Wilkes MM, Navickis RJ. A systematic review of the comparative safety of colloids. Arch Surg 2004;139:552–63.PubMedGoogle Scholar
  92. 92.
    Rolleman EJ, de Jong M, Valkema R, Kwekkeboom D, Kam B, Krenning EP. Inhibition of kidney uptake of radiolabeled somatostatin analogs: amino acids or gelofusine? J Nucl Med 2006;47:1730–1.PubMedGoogle Scholar
  93. 93.
    Prasad V, Fetscher S, Baum RP. Changing role of somatostatin receptor targeted drugs in NET: Nuclear Medicine's view. J Pharm Pharm Sci 2007;10:321s–37s.PubMedGoogle Scholar
  94. 94.
    Melis M, Bijster M, de Visser M, Konijnenberg MW, de Swart J, Rolleman EJ, et al. Dose-response effect of Gelofusine on renal uptake and retention of radiolabelled octreotate in rats with CA20948 tumours. Eur J Nucl Med Mol Imaging 2009. doi: 10.1007/s00259-009-1196-8
  95. 95.
    Christensen EI, Verroust PJ. Megalin and cubilin, role in proximal tubule function and during development. Pediatr Nephrol 2002;17:993–9.PubMedGoogle Scholar
  96. 96.
    Rolleman EJ, Krenning EP, Van Gameren A, Bernard BF, De Jong M. Uptake of [111In-DTPA0]octreotide in the rat kidney is inhibited by colchicine and not by fructose. J Nucl Med 2004;45:709–13.PubMedGoogle Scholar
  97. 97.
    Worthen HG. Renal toxicity of maleic acid in the rat: enzymatic and morphologic observations. Lab Invest 1963;12:791–801.PubMedGoogle Scholar
  98. 98.
    Verani RR, Brewer ED, Ince A, Gibson J, Bulger RE. Proximal tubular necrosis associated with maleic acid administration to the rat. Lab Invest 1982;46:79–88.PubMedGoogle Scholar
  99. 99.
    Boerman OC, Gotthardt M, Vegt E, Eek A, de Jong M, Oyen WJG. Fragments of albumin effectively reduce the renal uptake of radiolabelled peptides. Eur J Nucl Med Mol Imaging 2007;34 (Suppl 2):S240.Google Scholar
  100. 100.
    Vegt E, van Eerd JE, Eek A, Oyen WJ, Wetzels JF, de Jong M, et al. Reducing renal uptake of radiolabeled peptides using albumin fragments. J Nucl Med 2008;49:1506–11.PubMedGoogle Scholar
  101. 101.
    Andreassen CN, Grau C, Lindegaard JC. Chemical radioprotection: a critical review of amifostine as a cytoprotector in radiotherapy. Semin Radiat Oncol 2003;13:62–72.PubMedGoogle Scholar
  102. 102.
    Capizzi R. Amifostine: the preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies. Semin Oncol 1996;23:2–17.PubMedGoogle Scholar
  103. 103.
    Rolleman EJ, Forrer F, Bernard B, Bijster M, Vermeij M, Valkema R, et al. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [(177)Lu-DOTA(0),Tyr(3)]octreotate. Eur J Nucl Med Mol Imaging 2007;34:763–71.PubMedGoogle Scholar
  104. 104.
    Moulder JE, Fish BL, Cohen EP. Brief pharmacological intervention in experimental radiation nephropathy. Radiat Res 1998;150:535–41.PubMedGoogle Scholar
  105. 105.
    Molteni A, Moulder JE, Cohen EP, Fish BL, Taylor JM, Veno PA, et al. Prevention of radiation-induced nephropathy and fibrosis in a model of bone marrow transplant by an angiotensin II receptor blocker. Exp Biol Med (Maywood) 2001;226:1016–23.Google Scholar
  106. 106.
    Moulder JE, Fish BL, Cohen EP. Angiotensin II receptor antagonists in the treatment and prevention of radiation nephropathy. Int J Radiat Biol 1998;73:415–21.PubMedGoogle Scholar
  107. 107.
    Cohen EP, Fish BL, Moulder JE. Successful brief captopril treatment in experimental radiation nephropathy. J Lab Clin Med 1997;129:536–47.PubMedGoogle Scholar
  108. 108.
    Cohen EP. Radiation nephropathy after bone marrow transplantation. Kidney Int 2000;58:903–18.PubMedGoogle Scholar
  109. 109.
    Cohen EP, Irving AA, Drobyski WR, Klein JP, Passweg J, Talano JA, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. Int J Radiat Oncol Biol Phys 2008;70:1546–51.PubMedGoogle Scholar
  110. 110.
    Jaggi JS, Seshan SV, McDevitt MR, Sgouros G, Hyjek E, Scheinberg DA. Mitigation of radiation nephropathy after internal alpha-particle irradiation of kidneys. Int J Radiat Oncol Biol Phys 2006;64:1503–12.PubMedGoogle Scholar
  111. 111.
    Huang XR, Chen WY, Truong LD, Lan HY. Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease. J Am Soc Nephrol 2003;14:1738–47.PubMedGoogle Scholar
  112. 112.
    Rolleman EJ, Valkema R, Bernard B, Bijster M, Melis M, Krenning EP, et al. Additive effect of an angiontensin II blocker to kidney protection by lysine in a rat model of radiation nephropathy. Eur J Nucl Med Mol Imaging 2007;34(Suppl.2):S240.Google Scholar
  113. 113.
    de Visser M, Verwijnen SM, de Jong M. Update: improvement strategies for peptide receptor scintigraphy and radionuclide therapy. Cancer Biother Radiopharm 2008;23:137–57.PubMedGoogle Scholar
  114. 114.
    Reubi JC, Macke HR, Krenning EP. Candidates for peptide receptor radiotherapy today and in the future. J Nucl Med 2005;46(Suppl 1):67S–75S.PubMedGoogle Scholar
  115. 115.
    Wild D, Schmitt JS, Ginj M, Macke HR, Bernard BF, Krenning E, et al. DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging 2003;30:1338–47.PubMedGoogle Scholar
  116. 116.
    Cescato R, Schulz S, Waser B, Eltschinger V, Rivier JE, Wester HJ, et al. Internalization of sst2, sst3, and sst5 receptors: effects of somatostatin agonists and antagonists. J Nucl Med 2006;47:502–11.PubMedGoogle Scholar
  117. 117.
    Ginj M, Zhang H, Eisenwiener KP, Wild D, Schulz S, Rink H, et al. New pansomatostatin ligands and their chelated versions: affinity profile, agonist activity, internalization, and tumor targeting. Clin Cancer Res 2008;14:2019–27.PubMedGoogle Scholar
  118. 118.
    Ginj M, Zhang H, Waser B, Cescato R, Wild D, Wang X, et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors. Proc Natl Acad Sci USA 2006;103:16436–41.PubMedGoogle Scholar
  119. 119.
    Forrer F, Rolleman E, Bernard B, Valkema R, Krenning EP, De Jong M. Amifostine can reduce toxicity of targeted radionuclide therapy without affecting anti-tumour-effect. Eur J Nucl Med Mol Imaging 2006;33:S116.Google Scholar
  120. 120.
    Melis M, Krenning EP, Bernard BF, de Visser M, Rolleman E, de Jong M. Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences. Nucl Med Biol 2007;34:633–41.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Edgar J. Rolleman
    • 1
  • Marleen Melis
    • 1
  • Roelf Valkema
    • 1
  • Otto C. Boerman
    • 2
  • Eric P. Krenning
    • 1
  • Marion de Jong
    • 1
  1. 1.Department of Nuclear Medicine, V 220Erasmus MCRotterdamThe Netherlands
  2. 2.Department of Nuclear MedicineRadboud University HospitalNijmegenThe Netherlands

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