Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour.

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 [¹⁷⁷Lu-DOTA⁰-Tyr³]-octreotate given to nude mice xenografted with the human midgut carcinoid GOT1. The tumours in 22 out of 23 animals given therapeutic amounts showed dose-dependent, rapid complete remission. The diagnostic amount (0.5 MBq [¹⁷⁷Lu-DOTA⁰-Tyr³]-octreotate) did not influence tumour growth and was rapidly excreted. In contrast, the therapeutic amount (30 MBq [¹⁷⁷Lu-DOTA⁰-Tyr³]-octreotate) induced rapid tumour regression and entrapment of ¹⁷⁷Lu so that the activity concentration of ¹⁷⁷Lu 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⁻¹ and the tumours in animals treated with 30 MBq received 120 Gy. Therapeutic amounts of [¹⁷⁷Lu-DOTA⁰-Tyr³]-octreotate rapidly induced apoptosis and gradual development of fibrosis in grafted tumours. In conclusion, human midgut carcinoid xenografts can be cured by receptor-mediated 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.British Journal of Cancer (2005) 93, 1144–1151. doi:10.1038/sj.bjc.6602845 www.bjcancer.com Published online 25 October 2005 [ABSTRACT FROM AUTHOR]