Display options
Cite
Ilhan H, Wang H, Gildehaus FJ, et al. Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy. EJNMMI Res. 2016;6(1):64doi: 10.1186/s13550-016-0219-2.
Ilhan, H., Wang, H., Gildehaus, F. J., Wängler, C., Herrler, T., Todica, A., Schlichtiger, J., Cumming, P., Bartenstein, P., Hacker, M., & Haug, A. R. (2016). Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy. EJNMMI research, 6(1), 64. https://doi.org/10.1186/s13550-016-0219-2
Ilhan, Harun, et al. "Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy." EJNMMI research vol. 6,1 (2016): 64. doi: https://doi.org/10.1186/s13550-016-0219-2
Ilhan H, Wang H, Gildehaus FJ, Wängler C, Herrler T, Todica A, Schlichtiger J, Cumming P, Bartenstein P, Hacker M, Haug AR. Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy. EJNMMI Res. 2016 Dec;6(1):64. doi: 10.1186/s13550-016-0219-2. Epub 2016 Aug 11. PMID: 27515447; PMCID: PMC4980865.
Copy Download .nbib Format: NLM
Share it on

EJNMMI Res. 2016 Dec;6(1):64. doi: 10.1186/s13550-016-0219-2. Epub 2016 Aug 11.

Nephroprotective effects of enalapril after [177Lu]-DOTATATE therapy using serial renal scintigraphies in a murine model of radiation-induced nephropathy.

EJNMMI research

Harun Ilhan, Hao Wang, Franz J Gildehaus, Carmen Wängler, Tanja Herrler, Andrei Todica, Julia Schlichtiger, Paul Cumming, Peter Bartenstein, Marcus Hacker, Alexander R Haug

Affiliations

  1. Department of Nuclear Medicine, University of Munich, Munich, Germany.
  2. Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany.
  3. Department of Surgery, Campus Großhadern, University of Munich, Munich, Germany.
  4. Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, University of Vienna, Vienna, Austria.
  5. Department of Nuclear Medicine, University of Munich, Munich, Germany. [email protected].
  6. Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, University of Vienna, Vienna, Austria. [email protected].

PMID: 27515447 PMCID: PMC4980865 DOI: 10.1186/s13550-016-0219-2

Abstract

BACKGROUND: Radiation-induced nephropathy is still dose limiting in radionuclide therapy of neuroendocrine tumors. We investigated the nephroprotective potential of the angiotensine converting enzyme inhibiting drug enalpril after [177Lu]-DOTATATE therapy in a murine model of radiation-induced nephropathy by renal scintigraphy. At first, the appropriate therapy activity to induce nephropathy was identified. Baseline scintigraphy (n = 12) entailed 12-min dynamic acquisitions after injection of 25 MBq [99mTc]-MAG3, which was followed by radionuclide therapy at four escalating activities of [177Lu]-DOTATATE: group (Gp) 1: 10 MBq; Gp 2: 20 MBq; Gp 3: 40 MBq; Gp 4: 65 MBq. Follow-up [99mTc]-MAG3 scintigraphy was carried out at days 9, 23, 44, and 65. The treatment activity for the intervention arm was selected on the basis of histological examination and declining renal function. In the second part, daily administration by gavage of 10 mg/kg/d enalapril or water (control group) was initiated on the day of radionuclide therapy. Follow-up scintigraphy was carried out at days 9, 23, 44, 65, and 86. We also created a non-therapy control group to detect therapy-independent changes of renal function over time. For all scintigraphies, mean renogram curves were analyzed and the "fractional uptake rate" (FUR; %I.D./min ± SEM) of the tracer by the kidneys was calculated as an index of renal clearance.

RESULTS: At day 65 of follow-up, no significant change in the FUR relative to baseline (11.0 ± 0.3) was evident in radionuclide therapy groups 1 (11.2 ± 0.5) and 2 (10.1 ± 0.6), but FUR was significantly reduced in groups 3 (8.93 ± 0.6, p < 0.05) and 4 (6.0 ± 0.8, p < 0.01); we chose 40 MBq [177Lu]-DOTATATE (Gp 3) for the intervention study. Here, at the last day of follow-up (day 86), FUR was unaltered in enalapril-treated mice (11.8 ± 0.5) relative to the baseline group (12.4 ± 0.3) and non-therapy group (11.9 ± 0.8), whereas FUR in the control group had undergone a significant decline (9.3 ± 0.5; p < 0.01). Histological examination revealed prevention of kidney damage by enalapril treatment.

CONCLUSIONS: Treatment with enalapril is effective for nephroprotection during radionuclide therapy with [177Lu]-DOTATATE in mice. Although these results are only limitedly transferable to human studies, enalapril might serve as a promising drug in the mitigation of nephropathy following treatment with [177Lu]-DOTATATE.

Keywords: Enalapril; Neuroendocrine tumors; Radiation-induced nephropathy; Tc-99m-MAG3 scintigraphy; [177Lu]-DOTATATE

References

  1. Int J Radiat Oncol Biol Phys. 1993 Sep 1;27(1):93-9 - PubMed
  2. Exp Biol Med (Maywood). 2001 Dec;226(11):1016-23 - PubMed
  3. Eur J Nucl Med. 2001 Oct;28(10):1552-4 - PubMed
  4. Eur J Nucl Med Mol Imaging. 2004 Jul;31(7):1038-46 - PubMed
  5. Eur J Nucl Med Mol Imaging. 2007 Feb;34(2):219-27 - PubMed
  6. Ann Oncol. 2001 Jul;12(7):941-5 - PubMed
  7. Nephron. 1993;64(2):249-55 - PubMed
  8. Am J Kidney Dis. 2001 Apr;37(4):847-51 - PubMed
  9. J Nucl Med. 1996 Aug;37(8):1388-92 - PubMed
  10. Cancer Biother Radiopharm. 2007 Feb;22(1):40-9 - PubMed
  11. Int J Cancer. 2001 Dec 15;94(6):873-7 - PubMed
  12. J Nucl Med. 2005 Jan;46 Suppl 1:99S-106S - PubMed
  13. Eur J Nucl Med. 2001 Sep;28(9):1319-25 - PubMed
  14. J Clin Oncol. 2008 May 1;26(13):2124-30 - PubMed
  15. J Clin Oncol. 2010 Apr 1;28(10):1652-9 - PubMed
  16. Eur J Nucl Med Mol Imaging. 2003 Feb;30(2):207-16 - PubMed
  17. Internist (Berl). 2012 Feb;53(2):161-6 - PubMed
  18. EJNMMI Res. 2016 Dec;6(1):13 - PubMed
  19. Cancer Res. 1997 Feb 15;57(4):659-71 - PubMed
  20. J Nucl Med. 2005 Oct;46(10 ):1696-700 - PubMed
  21. Eur J Nucl Med Mol Imaging. 2007 May;34(5):763-71 - PubMed
  22. J Nucl Med. 2005 Jan;46 Suppl 1:62S-6S - PubMed
  23. Nephrol Dial Transplant. 2001 May;16(5):1082-3 - PubMed
  24. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22 - PubMed
  25. Eur J Nucl Med. 1999 Nov;26(11):1439-47 - PubMed
  26. Am J Physiol Renal Physiol. 2010 Feb;298(2):F454-60 - PubMed
  27. Transplantation. 2010 Jan 15;89(1):40-6 - PubMed
  28. EJNMMI Res. 2012 Jan 20;2:2 - PubMed
  29. Am J Physiol Renal Physiol. 2007 Oct;293(4):F1408-12 - PubMed
  30. Nucl Med Biol. 2015 Oct;42(10):770-9 - PubMed
  31. J Clin Oncol. 2011 Jun 10;29(17):2416-23 - PubMed
  32. Eur J Nucl Med. 2000 Nov;27(11):1708-13 - PubMed
  33. Eur J Nucl Med Mol Imaging. 2011 Feb;38(2):302-11 - PubMed
  34. Semin Nephrol. 2003 Sep;23(5):486-99 - PubMed
  35. Eur J Nucl Med Mol Imaging. 2003 Jun;30(6):917-20 - PubMed
  36. J Nucl Med. 2010 Dec;51(12 ):1962-8 - PubMed
  37. J Lab Clin Med. 2002 Apr;139(4):251-7 - PubMed
  38. Radiat Res. 1992 Dec;132(3):346-50 - PubMed
  39. Kidney Int. 2006 Aug;70(3):507-14 - PubMed
  40. Eur J Nucl Med Mol Imaging. 2003 Jan;30(1):9-15 - PubMed
  41. Eur J Nucl Med Mol Imaging. 2008 Oct;35(10):1847-56 - PubMed

Publication Types