학술논문

Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour.
Document Type
Article
Source
British Journal of Cancer. 11/14/2005, Vol. 93 Issue 10, p1144-1151. 8p. 2 Diagrams, 2 Charts, 4 Graphs.
Subject
*SOMATOSTATIN
*RADIOTHERAPY
*THERAPEUTICS
*NEUROENDOCRINE tumors
*GASTROINTESTINAL hormones
*TUMOR growth
*CLINICAL medicine
Language
ISSN
0007-0920
Abstract
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]