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

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 [(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 dose-dependent, 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(-1) 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 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.

• Authors: L Kölby, P Bernhardt, V Johanson, A Schmitt, H Ahlman, E Forssell-Aronsson, H Mäcke, O Nilsson
• Journal: British journal of cancer (Br J Cancer) Vol. 93 Issue 10 Pg. 1144-51 (Nov 14 2005) ISSN: 0007-0920 [Print] England
• PMID: 16251870 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 177Lu-octreotide, DOTA(0)-Tyr(3)-
• Receptors, Somatostatin
• Octreotide

Topics

• Animals
• Carcinoid Tumor (drug therapy, metabolism, radiotherapy)
• Humans
• Mice
• Mice, Nude
• Octreotide (analogs & derivatives, pharmacokinetics, therapeutic use)
• Receptors, Somatostatin (metabolism)
• Xenograft Model Antitumor Assays