title: Uptake kinetics of the somatostatin receptor ligand [86Y]DOTA-DPhe1- Tyr3-octreotide ([86Y]SMT487) using positron emission tomography in non-human primates and calculation of radiation doses of the 90Y-labelled analogue.
abstract: [90Y]DOTA-DPhe1-Tyr3-octreotide ([90Y]-SMT487) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tumours. In order to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [86Y]DOTA-DPhe1-Tyr3-octreotide was synthesised and its uptake measured in baboons using positron emission tomography (PET). [86Y]DOTA-DPhe1-Tyr3-octreotide was administered at two different peptide concentrations, namely 2 and 100 microg peptide per m2 body surface. The latter concentration corresponded to a radiotherapeutic dose. In a third protocol [86Y]DOTA-DPhe1-Tyr3-octreotide was injected in conjunction with a simultaneous infusion of an amino acid solution that was high in l-lysine in order to lower the renal uptake of radioyttrium. Quantitative whole-body PET scans were recorded to measure the uptake kinetics for kidneys, liver, lung and bone. The individual absolute uptake kinetics were used to calculate the radiation doses for [90Y]DOTA-DPhe1-Tyr3-octreotide according to the MIRD recommendations extrapolated to a 70-kg human. The highest radiation dose was received by the kidneys, with 2.1-3.3 mGy per MBq [90Y]DOTA-DPhe1-Tyr3-octreotide injected. For the 100 microg/m2 SMT487 protocol with amino acid co-infusion this dose was about 20%-40% lower than for the other two treatment protocols. The liver and the red bone marrow received doses ranging from 0.32 to 0.53 mGy and 0.03 to 0.07 mGy per MBq [90Y]DOTA-DPhe1-Tyr3-octreotide, respectively. The average effective dose equivalent amounted to 0. 23-0.32 mSv/MBq. The comparatively low estimated radiation doses to normal organs support the initiation of clinical phase I trials with [90Y]DOTA-DPhe1-Tyr3-octreotide in patients with somatostatin receptor-expressing tumours.
authors: Institut für Nuklearchemie, Forschungszentrum Jülich, Germany.
authors: F
authors: F
authors: Rösch
authors: H
authors: H
authors: Herzog
authors: B
authors: B
authors: Stolz
authors: J
authors: J
authors: Brockmann
authors: M
authors: M
authors: Köhle
authors: H
authors: H
authors: Mühlensiepen
authors: P
authors: P
authors: Marbach
authors: H W
authors: HW
authors: Müller-Gärtner
mesh_terms: D000758:Anesthesia; D000818:Animals; D005260:Female; D007091:Image Processing, Computer-Assisted; D008024:Ligands; D008297:Male; D015282:Octreotide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D010215:Papio; D011786:Quality Control; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D017481:Receptors, Somatostatin / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics
chemical_list: D008024:Ligands; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; D015021:Yttrium Radioisotopes; D015282:Octreotide; C106246:Edotreotide