Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion

Eur J Nucl Med Mol Imaging. 2013 Dec;40(12):1853-60. doi: 10.1007/s00259-013-2504-x. Epub 2013 Jul 18.

Abstract

Purpose: The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion.

Methods: The whole-blood clearance of (177)Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion.

Results: LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion.

Conclusion: The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acids / administration & dosage*
  • Amino Acids / pharmacology*
  • Biological Transport / drug effects
  • Chemoradiotherapy / adverse effects
  • Cohort Studies
  • Cytoprotection / drug effects*
  • Feasibility Studies
  • Female
  • Humans
  • Kidney / drug effects*
  • Kidney / radiation effects
  • Male
  • Middle Aged
  • Octreotide / adverse effects
  • Octreotide / analogs & derivatives*
  • Octreotide / blood
  • Octreotide / pharmacokinetics
  • Octreotide / therapeutic use
  • Organometallic Compounds / adverse effects*
  • Organometallic Compounds / blood
  • Organometallic Compounds / pharmacokinetics*
  • Organometallic Compounds / therapeutic use
  • Receptors, Peptide / metabolism
  • Retrospective Studies
  • Time Factors
  • Young Adult

Substances

  • Amino Acids
  • Organometallic Compounds
  • Receptors, Peptide
  • lutetium Lu 177 dotatate
  • Octreotide