title: Molecular imaging of reduced renal uptake of radiolabelled [DOTA0,Tyr3]octreotate by the combination of lysine and Gelofusine in rats.
abstract: OBJECTIVE
  In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, kidney uptake of radiolabelled compound is the major dose-limiting factor. We studied the effects of Gelofusine (20 mg) and lysine (100 mg) and the combination of both after injection of therapeutic doses of radiolabelled [DOTA0,Tyr3]octreotate (60 MBq 111In or 555 MBq 177Lu labelled to 15 microg peptide) in male Lewis rats.
  
  
  METHODS
  Kidney uptake was measured by single photon emission computed tomography (SPECT) scans with a four-headed multi-pinhole camera (NanoSPECT) at 24 h, 5 and 7 days p. i. and was quantified by volume of interest analysis. For validation the activity concentration in the dissected kidneys was also determined ex vivo using a gamma counter and a dose calibrator.
  
  
  RESULTS
  Gelofusine and lysine both reduced kidney uptake of [177Lu-DOTA0,Tyr3]octreotate significantly by about 40% at all time points. The combination of Gelofusine and lysine resulted in a 62% inhibition of kidney uptake (p < 0.01 vs. lysine alone). A weak but significant dose-response relationship for Gelofusine, but not for lysine, was found. In a study with [111In-DOTA0,Tyr3]octreotate, conclusions drawn from NanoSPECT data were confirmed by biodistribution data.
  
  
  CONCLUSIONS
  We conclude that rat kidney uptake of radiolabelled somatostatin analogues can be monitored for a longer period in the same animal using animal SPECT. Gelofusine and lysine had equal potential to reduce kidney uptake of therapeutic doses of [177Lu-DOTA0,Tyr3]octreotate. The combination of these compounds caused a significantly larger reduction than lysine or Gelofusine alone and may therefore offer new possibilities in PRRT. The NanoSPECT data were validated by standard biodistribution experiments.
authors.affiliation: Department Nuclear Medicine, Room L244, Erasmus MC's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. e.rolleman@erasmusmc.nl
authors.forename: E J
authors.initials: EJ
authors.lastname: Rolleman
authors.forename: B F
authors.initials: BF
authors.lastname: Bernard
authors.forename: W A P
authors.initials: WA
authors.lastname: Breeman
authors.forename: F
authors.initials: F
authors.lastname: Forrer
authors.forename: E
authors.initials: E
authors.lastname: de Blois
authors.forename: J
authors.initials: J
authors.lastname: Hoppin
authors.forename: M
authors.initials: M
authors.lastname: Gotthardt
authors.forename: O C
authors.initials: OC
authors.lastname: Boerman
authors.forename: E P
authors.initials: EP
authors.lastname: Krenning
authors.forename: M
authors.initials: M
authors.lastname: de Jong
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004342:Drug Hypersensitivity; D006801:Humans; D007668:Kidney / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D008187:Lutetium / Q000493:pharmacokinetics; D008239:Lysine / Q000494:pharmacology*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D011097:Polygeline / Q000009:adverse effects / Q000494:pharmacology*; D011868:Radioisotopes / Q000493:pharmacokinetics; D051381:Rats; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D009942:Organometallic Compounds; D011868:Radioisotopes; D008187:Lutetium; D011097:Polygeline; C447941:lutetium Lu 177 dotatate; D008239:Lysine; D015282:Octreotide