title: Renal function affects absorbed dose to the kidneys and haematological toxicity during ¹⁷⁷Lu-DOTATATE treatment.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment.
  
  
  METHODS
  The study included 51 patients with an advanced neuroendocrine tumour who received (177)Lu-DOTATATE treatment during 2006 - 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 - 8.2 GBq) was given at intervals of 6 - 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated.
  
  
  RESULTS
  A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of (177)Lu in the whole body (range 0.89 - 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53).
  
  
  CONCLUSIONS
  Patients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during (177)Lu-DOTATATE treatment. The study confirms the tolerability of PRRT in patients with an advanced neuroendocrine tumour but indicates that patients with inferior renal function are at risk of being exposed to higher absorbed doses to normal tissue on treatment.
authors: Department of Oncology, Sahlgrenska University Hospital, SE 413 45, Göteborg, Sweden, johanna.svensson@oncology.gu.se.
authors: Johanna
authors: J
authors: Svensson
authors: Gertrud
authors: G
authors: Berg
authors: Bo
authors: B
authors: Wängberg
authors: Maria
authors: M
authors: Larsson
authors: Eva
authors: E
authors: Forssell-Aronsson
authors: Peter
authors: P
authors: Bernhardt
mesh_terms: D000368:Aged; D001769:Blood / Q000187:drug effects* / Q000528:radiation effects; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011878:Radiotherapy / Q000009:adverse effects*; D065608:Renal Reabsorption
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
references: Eur J Nucl Med Mol Imaging. 2012 Feb;39 Suppl 1:S103-12
references: 22388631
references: J Nucl Med. 2005 Jan;46 Suppl 1:83S-91S
references: 15653656
references: Cancer Biother Radiopharm. 2005 Feb;20(1):47-51
references: 15778580
references: EJNMMI Res. 2012 Sep 24;2(1):49
references: 23006939
references: World J Surg. 2010 Jun;34(6):1368-72
references: 20066413
references: Eur J Nucl Med Mol Imaging. 2010 Feb;37(2):212-25
references: 19727718
references: Eur J Nucl Med Mol Imaging. 2009 Jul;36(7):1138-46
references: 19247653
references: Cancer. 2010 Feb 15;116(4 Suppl):1084-92
references: 20127957
references: Biomed Res Int. 2013;2013:935351
references: 23865075
references: J Nephrol. 2011 Jan-Feb;24(1):23-34
references: 20437401
references: Lancet. 2012 Jan 14;379(9811):165-80
references: 21840587
references: Cancer Biother Radiopharm. 2012 Nov;27(9):593-9
references: 23009580
references: Eur J Nucl Med. 2001 Sep;28(9):1319-25
references: 11585290
references: J Nucl Med. 2013 Jan;54(1):33-41
references: 23223392
references: J Clin Oncol. 2008 May 1;26(13):2124-30
references: 18445841
references: J Clin Oncol. 2005 Aug 1;23(22):4897-904
references: 16051944
references: Phys Med Biol. 1979 Jan;24(1):176-80
references: 372956
references: Semin Nucl Med. 2010 Mar;40(2):78-88
references: 20113677
references: Semin Nucl Med. 2011 Jan;41(1):61-72
references: 21111860
references: Ann ICRP. 2008;38(3):7-96
references: 19285593
references: Q J Nucl Med Mol Imaging. 2011 Apr;55(2):205-21
references: 21386791
references: J Nucl Med. 2006 Sep;47(9):1467-75
references: 16954555
references: Theranostics. 2012;2(5):459-71
references: 22768026
references: Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22
references: 2032882
references: Lakartidningen. 2013 May 22-28;110(21):1021-4
references: 23805765
references: Med Phys. 2009 Feb;36(2):612-9
references: 19292001
references: Cancer Biother Radiopharm. 2004 Jun;19(3):363-70
references: 15285884
references: Ann Nucl Med. 2013 Jan;27(1):74-7
references: 22961123
references: Eur J Nucl Med Mol Imaging. 2005 Oct;32(10):1136-43
references: 15912401
references: J Nucl Med. 2013 Nov;54(11):1857-61
references: 24009272
references: J Nucl Med. 2011 Sep;52(9):1361-8
references: 21795361
references: Acta Oncol. 2012 Jan;51(1):86-96
references: 21961497
references: Eur J Nucl Med Mol Imaging. 2011 Dec;38(12):2125-35
references: 21892623
references: Eur J Nucl Med Mol Imaging. 2008 Oct;35(10):1847-56
references: 18427807