[Lu-177-DOTA(0),Tyr(3)]octreotate: comparison with [In-111-DTPA(0)]octreotide in patients

The somatostatin analogue [DOTA(0),Tyr(3)]octreotate has a nine-fold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA0, Tyr(3)]octreotide. Also, labelled with the beta- and gamma-emitting radionu clide 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 somatostati n receptor-mediated radiotherapy, we decided to compare [Lu-177-DOTA(0),Tyr (3)]octreotate (Lu-177-octreotate) with [In-111-DTPA(0)]octreotide (In-111- octreotide) in six patients with somatostatin receptor-positive tumours. Pl asma radioactivity after Lu-177-octreotate expressed as a percentage of the injected dose was comparable with that after In-111-octreotide. Urinary ex cretion of radioactivity was significantly lower than after In-111-octreoti de, averaging 64% after 24 h. The uptake after 24 h, expressed as a percent age of the injected dose of Lu-177-octreotate, was comparable to that after In-111-octreotide for kidneys, spleen and liver, but was three- to fourfol d higher for four of five tumours. The spleen and kidneys received the high est 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 t he radionuclide-coupled somatostatin analogues that are currently available for somatostatin receptor-mediated radiotherapy, Lu-177-octreotate potenti ally represents an important improvement. Higher absorbed doses can be achi eved to most tumours, with about equal doses to potentially dose-limiting o rgans; furthermore, the lower tissue penetration range of Lu-177 as compare d with Y-90 may be especially important for small tumours.