This study shows that (177)Lu-labeled [DOTA(0),Tyr(3)]octreotate has therapeutic potential for SCLC. The study also points out the importance of optimal labeling efficiency since the high bone marrow uptake of free lutetium ions can be controlled by a high peptide-bound fraction.

Somatostatin receptor (sstr)-mediated radiation therapy is a new therapeutic modality for neuroendocrine (NE) tumours. High expression of sstr in NE tumours leads to tumour-specific uptake of radiolabelled somatostatin analogues and high absorbed doses. In this study, we present the first optimised radiation therapy via sstr using [ 177 Lu-DOTA 0 -Tyr 3 ]-octreotate given to nude mice xenografted with the human midgut carcinoid GOT1. The tumours in 22 out of 23 animals given therapeutic amounts showed dosedependent, rapid complete remission. The diagnostic amount (0.5 MBq [ 177 Lu-DOTA 0 -Tyr 3 ]-octreotate) did not influence tumour growth and was rapidly excreted. In contrast, the therapeutic amount (30 MBq [ 177 Lu-DOTA 0 -Tyr 3 ]-octreotate) induced rapid tumour regression and entrapment of 177 Lu so that the activity concentration of 177 Lu remained high, 7 and 13 days after injection. The entrapment phenomenon increased the absorbed dose to tumours from 1.6 to 4.0 Gy MBq À1 and the tumours in animals treated with 30 MBq received 120 Gy. Therapeutic amounts of [ 177 Lu-DOTA 0 -Tyr 3 ]-octreotate rapidly induced apoptosis and gradual development of fibrosis in grafted tumours. In conclusion, human midgut carcinoid xenografts can be cured by receptormediated radiation therapy by optimising the uptake of radioligand and taking advantage of the favourable change in biokinetics induced by entrapment of radionuclide in the tumours.

The low tumor-to-lung and tumor-to-liver activity concentration ratios for (99m)Tc-depreotide could result in a lower detection rate of SCLC with this compound versus (111)In-DTPA-octreotide. (177)Lu-DOTA-Tyr(3)-octreotate gave the highest tumor-activity concentration, and has, thus, the best properties for therapy.

The biodistribution of 211At and 125I- differed in this animal model. The higher mean absorbed dose from 211At in several organs than in tumor tissue restricts the possibility of using free 211At for therapy of ATC.

The aim of this study was to compare the tumor uptake versus time and the tumor response in nude mice transplanted with a human midgut carcinoid (GOT1), when treated with either [(177)Lu-DOTA(0),Tyr(3)]-octreotide or [(177)Lu-DOTA(0),Tyr(3)]-octreotate and to evaluate if plasma chromogranin A (P-CgA) was a reliable marker of tumor response. The tumor uptake and retention of activity of a single intravenous (i.v.) dose (15 MBq) of [(177)Lu-DOTA(0),Tyr(3)]-octreotate or [(177)Lu-DOTA(0),Tyr(3)]-octreotide were compared in nude mice xenografted with GOT1. The activity concentration 24 hours after injection was significantly higher in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate versus [(177)Lu-DOTA(0),Tyr(3)]-octreotide (16%+/-1.4% of injected activity per gram [%IA/g] vs. 8.1%+/-2.1% IA/g, mean +/- standard error of the mean) (p=0.00061). The mean absorbed dose was higher in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate (46+/-4.3 vs. 17 +/- 3.4 Gy). The reduction of tumor volume was accordingly more prominent in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate than in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotide (p=0.003). The mean tumor volume for animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate was reduced to 3% of its initial value. P-CgA values were strongly correlated with tumor volume. Octreotate seems to be a more suitable somatostatin analog than octreotide for receptor-mediated radiation therapy. P-CgA is a simple, accurate method for the estimation of tumor response in this animal model.