title: The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity.
abstract: Peptide receptor-targeted radionuclide therapy is nowadays also being performed with DOTA-conjugated peptides, such as [DOTA(0),Tyr(3)]octreotate, labelled with radionuclides like (177)Lu. The incorporation of (177)Lu is typically >/=99.5%; however, since a total patient dose can be as high as 800 mCi, the amount of free (177)Lu(3+) (= non-DOTA-incorporated) can be substantial. Free (177)Lu(3+) accumulates in bone with unwanted irradiation of bone marrow as a consequence. (177)Lu-DTPA is reported to be stable in serum in vitro, and in vivo it has rapid renal excretion. Transforming free Lu(3+) to Lu-DTPA might reroute this fraction from accumulation in bone to renal clearance. We therefore investigated: (a) the biodistribution in rats of (177)LuCl(3), [(177)Lu-DOTA(0),Tyr(3)]octreotate and (177)Lu-DTPA; (b) the possibilities of complexing the free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate to (177)Lu-DTPA prior to intravenous injection; and (c) the effects of free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate, in the presence and absence of DTPA, on the biodistribution in rats. (177)LuCl(3) had high skeletal uptake (i.e. 5% ID per gram femur, with localization mainly in the epiphyseal plates) and a 24-h total body retention of 80% injected dose (ID). [(177)Lu-DOTA(0),Tyr(3)]octreotate had high and specific uptake in somatostatin receptor-positive tissues, and 24-h total body retention of 19% ID. (177)Lu-DTPA had rapid renal clearance, and 24-h total body retention of 4% ID. Free (177)Lu(3+) in [(177)Lu-DOTA(0),Tyr(3)]octreotate could be complexed to (177)Lu-DTPA. Accumulation of (177)Lu in femur, blood, liver and spleen showed a dose relation to the amount of free (177)Lu(3+), while these accumulations could be normalized by the addition of DTPA. After labelling [DOTA(0),Tyr(3)]octreotate with (177)Lu the addition of DTPA prior to intravenous administration of [(177)Lu-DOTA(0),Tyr(3)]octreotate is strongly recommended.
authors.affiliation: Department of Nuclear Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. breeman@nuge.azr.nl
authors.forename: Wouter A P
authors.initials: WA
authors.lastname: Breeman
authors.forename: Katy
authors.initials: K
authors.lastname: van der Wansem
authors.forename: Bert F
authors.initials: BF
authors.lastname: Bernard
authors.forename: Arthur
authors.initials: A
authors.lastname: van Gameren
authors.forename: Jack L
authors.initials: JL
authors.lastname: Erion
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
authors.forename: M
authors.initials: M
authors.lastname: de Jong
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000008:administration & dosage / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007668:Kidney / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008187:Lutetium / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives; D009928:Organ Specificity; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000008:administration & dosage*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D011868:Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D011874:Radiometry / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D011837:Radiation-Protective Agents; D011868:Radioisotopes; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008187:Lutetium; D004369:Pentetic Acid; C447941:lutetium Lu 177 dotatate; D015282:Octreotide