title: 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.affiliation: Department of Surgery, Lundberg Laboratory for Cancer Research, Institute for Surgical Sciences, Göteborg University, Sahlgrenska University Hospital, Sweden. lars.kolby@surgery.gu.se
authors.forename: L
authors.initials: L
authors.lastname: Kölby
authors.forename: P
authors.initials: P
authors.lastname: Bernhardt
authors.forename: V
authors.initials: V
authors.lastname: Johanson
authors.forename: A
authors.initials: A
authors.lastname: Schmitt
authors.forename: H
authors.initials: H
authors.lastname: Ahlman
authors.forename: E
authors.initials: E
authors.lastname: Forssell-Aronsson
authors.forename: H
authors.initials: H
authors.lastname: Mäcke
authors.forename: O
authors.initials: O
authors.lastname: Nilsson
mesh_terms: D000818:Animals; D002276:Carcinoid Tumor / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015282:Octreotide / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D017481:Receptors, Somatostatin; D015282:Octreotide