Comparison of [177Lu-DOTA0,Tyr3]-octreotate and [177Lu-DOTA0,Tyr3]-octreotide for receptor-mediated radiation therapy of the xenografted human midgut carcinoid tumor GOT1.
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.
Swärd
Christina
C
The Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg, Sweden.
Bernhardt
Peter
P
Johanson
Viktor
V
Schmitt
Anneli
A
Ahlman
Håkan
H
Stridsberg
Mats
M
Forssell-Aronsson
Eva
E
Nilsson
Ola
O
Kölby
Lars
L
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
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