title: Rapid blood clearance and lack of long-term renal toxicity of 177Lu-DOTATATE enables shortening of renoprotective amino acid infusion.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Cancer Imaging, Peter MacCallum Cancer Centre, St Andrews Place, Melbourne, 3002, Australia, kashyapkr@gmail.com.
authors.forename: Raghava
authors.initials: R
authors.lastname: Kashyap
authors.forename: Price
authors.initials: P
authors.lastname: Jackson
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hofman
authors.forename: Peter
authors.initials: P
authors.lastname: Eu
authors.forename: Jean-Mathieu
authors.initials: JM
authors.lastname: Beauregard
authors.forename: Diana
authors.initials: D
authors.lastname: Zannino
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000008:administration & dosage* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D059248:Chemoradiotherapy / Q000009:adverse effects; D015331:Cohort Studies; D019610:Cytoprotection / Q000187:drug effects*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000378:metabolism; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000596:Amino Acids; D009942:Organometallic Compounds; D018000:Receptors, Peptide; C447941:lutetium Lu 177 dotatate; D015282:Octreotide