1. ¹Department of Surgery, Lundberg Laboratory for Cancer Research, Institute for Surgical Sciences, Göteborg University, Sahlgrenska University Hospital, Göteborg SE-413 45, Sweden
2. ²Department of Radiation Physics, Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
3. ³Division of Radiological Chemistry, University Hospital, Basel, Switzerland
4. ⁴Departments of Pathology, Lundberg Laboratory for Cancer Research, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden

Correspondence: Dr L Kölby, E-mail: lars.kolby@surgery.gu.se

Received 29 June 2005; Revised 19 September 2005; Accepted 29 September 2005; Published online 25 October 2005.

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.