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

[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 μg 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 μg/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. Received 26 September and in revised form 18 November 1998