title: [177Lu-DOTAOTyr3]octreotate: comparison with [111In-DTPAo]octreotide in patients.
abstract: The somatostatin analogue [DOTA0,Tyr3]octreotate has a nine-fold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0, Tyr3]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide lutetium-177, this compound has been shown to have a very favourable impact on tumour regression and animal survival in a rat model. Because of these reported advantages over the analogues currently used for somatostatin receptor-mediated radiotherapy, we decided to compare [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) with [111In-DTPA0]octreotide (111In-octreotide) in six patients with somatostatin receptor-positive tumours. Plasma radioactivity after 177Lu-octreotate expressed as a percentage of the injected dose was comparable with that after 111In-octreotide. Urinary excretion of radioactivity was significantly lower than after 111In-octreotide, averaging 64% after 24 h. The uptake after 24 h, expressed as a percentage of the injected dose of 177Lu-octreotate, was comparable to that after 111In-octreotide for kidneys, spleen and liver, but was three- to fourfold higher for four of five tumours. The spleen and kidneys received the highest absorbed doses. The doses to the kidneys were reduced by a mean of 47% after co-infusion of amino acids. It is concluded that in comparison with the radionuclide-coupled somatostatin analogues that are currently available for somatostatin receptor-mediated radiotherapy, 177Lu-octreotate potentially represents an important improvement. Higher absorbed doses can be achieved to most tumours, with about equal doses to potentially dose-limiting organs; furthermore, the lower tissue penetration range of 177Lu as compared with 90Y may be especially important for small tumours.
authors.affiliation: Department of Nuclear Medicine, University Hospital Rotterdam, The Netherlands. djkwekkeboom@hotmail.com
authors.forename: D J
authors.initials: DJ
authors.lastname: Kwekkeboom
authors.forename: W H
authors.initials: WH
authors.lastname: Bakker
authors.forename: P P
authors.initials: PP
authors.lastname: Kooij
authors.forename: M W
authors.initials: MW
authors.lastname: Konijnenberg
authors.forename: A
authors.initials: A
authors.lastname: Srinivasan
authors.forename: J L
authors.initials: JL
authors.lastname: Erion
authors.forename: M A
authors.initials: MA
authors.lastname: Schmidt
authors.forename: J L
authors.initials: JL
authors.lastname: Bugaj
authors.forename: M
authors.initials: M
authors.lastname: de Jong
authors.forename: E P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D008187:Lutetium / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging* / Q000532:radiotherapy; D015282:Octreotide / Q000031:analogs & derivatives; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D011829:Radiation Dosage; D011868:Radioisotopes / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000032:analysis*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D013004:Somatostatin; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; C081788:pentetreotide; D015282:Octreotide