[177Lu-DOTA0,Tyr3]octreotate:: comparison with [111In-DTPA0]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 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 [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. Plasma radioactivity after Lu-177-octreotate expressed as a percentage of the injected dose was comparable with that after In-111-octreotide. Urinary excretion of radioactivity was significantly lower than after In-111-octreotide, averaging 64% after 24 h. The uptake after 24 h, expressed as a percentage 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 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, Lu-177-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 Lu-177 as compared with Y-90 may be especially important for small tumours.