Uptake kinetics of the somatostatin receptor ligand [Y-86]DOTA-DPhe(1)-Tyr(3)-octreotide ([Y-86]SMT487) using positron emission tomography in non-human primates and calculation of radiation doses of the Y-90-labelled analogue

[Y-90] DOTA-DPhe(1)-Tyr(3)-octreotide ([Y-90]-SMT387) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tu mours. In order to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [Y-86]DOTA-DPhe( 1)-Tyr(3)-octreotide was synthesised and its uptake measured in baboons usi ng positron emission tomography (PET), [Y-86]DOTA-DPhe (1)-Tyr(3)-octreotid e was administered at two different peptide concentrations, namely 2 and 10 0 mu g peptide per m2 body surface. The latter concentration corresponded t o a radiotherapeutic dose. In a third protocol [Y-86]DOTA-DPhe(1)-Tyr(3)-oc treotide was injected in conjunction with a simultaneous infusion of an ami no acid solution that was high in L-lysine in order to lower the renal upta ke of radioyttrium. Quantitative whole-body PET scans were recorded to meas ure the uptake kinetics for kidneys, liver, lung and bone, The individual a bsolute uptake kinetics were used to calculate the radiation doses for [Y-9 0]DOTA-DPhe(1)-Tyr(3)-octreotide according to the MIRD recommendations extr apolated to a 70-kg human. The highest radiation dose was received by the k idneys, with 2.1-3.3 mGy per MBq [Y-90]DOTA-DPhe(1)-Tyr(3)-octreotide injec ted. For the 100 mu g/m(2) 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 [Y-90]DOTA-DPhe(1)-Tyr(3)-octreotide, resp ectively. The average effective dose equivalent amounted to 0.23-0.32 mSv/M Bq, The comparatively low estimated radiation doses to normal organs suppor t the initiation of clinical phase I trials with [Y-90]DOTA-DPhe(1)-Try(3)- octreotide in patients with somatostatin receptor-expressing tumours.