title: Comparison of [177Lu-DOTA0,Tyr3]-octreotate and [177Lu-DOTA0,Tyr3]-octreotide for receptor-mediated radiation therapy of the xenografted human midgut carcinoid tumor GOT1.
abstract: The aim of this study was to compare the tumor uptake versus time and the tumor response in nude mice transplanted with a human midgut carcinoid (GOT1), when treated with either [(177)Lu-DOTA(0),Tyr(3)]-octreotide or [(177)Lu-DOTA(0),Tyr(3)]-octreotate and to evaluate if plasma chromogranin A (P-CgA) was a reliable marker of tumor response. The tumor uptake and retention of activity of a single intravenous (i.v.) dose (15 MBq) of [(177)Lu-DOTA(0),Tyr(3)]-octreotate or [(177)Lu-DOTA(0),Tyr(3)]-octreotide were compared in nude mice xenografted with GOT1. The activity concentration 24 hours after injection was significantly higher in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate versus [(177)Lu-DOTA(0),Tyr(3)]-octreotide (16%+/-1.4% of injected activity per gram [%IA/g] vs. 8.1%+/-2.1% IA/g, mean +/- standard error of the mean) (p=0.00061). The mean absorbed dose was higher in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate (46+/-4.3 vs. 17 +/- 3.4 Gy). The reduction of tumor volume was accordingly more prominent in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate than in animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotide (p=0.003). The mean tumor volume for animals given [(177)Lu-DOTA(0),Tyr(3)]-octreotate was reduced to 3% of its initial value. P-CgA values were strongly correlated with tumor volume. Octreotate seems to be a more suitable somatostatin analog than octreotide for receptor-mediated radiation therapy. P-CgA is a simple, accurate method for the estimation of tumor response in this animal model.
authors.affiliation: The Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Swärd
authors.forename: Peter
authors.initials: P
authors.lastname: Bernhardt
authors.forename: Viktor
authors.initials: V
authors.lastname: Johanson
authors.forename: Anneli
authors.initials: A
authors.lastname: Schmitt
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlman
authors.forename: Mats
authors.initials: M
authors.lastname: Stridsberg
authors.forename: Eva
authors.initials: E
authors.lastname: Forssell-Aronsson
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
authors.forename: Lars
authors.initials: L
authors.lastname: Kölby
mesh_terms: D000818:Animals; D002276:Carcinoid Tumor / Q000532:radiotherapy*; D053379:Chromogranin A / Q000097:blood; D006801:Humans; D007414:Intestinal Neoplasms / Q000532:radiotherapy*; D008187:Lutetium / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D017481:Receptors, Somatostatin / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C504257:177Lu-octreotide, DOTA(0)-Tyr(3)-; D053379:Chromogranin A; D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; D008187:Lutetium; C447941:lutetium Lu 177 dotatate; D015282:Octreotide