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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.
AuthorsChristina Swärd, Peter Bernhardt, Viktor Johanson, Anneli Schmitt, Håkan Ahlman, Mats Stridsberg, Eva Forssell-Aronsson, Ola Nilsson, Lars Kölby
JournalCancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 23 Issue 1 Pg. 114-20 (Feb 2008) ISSN: 1084-9785 [Print] United States
PMID18298335 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • (177lutetium-DOTA(O)Tyr3)octreotate
  • 177Lu-octreotide, DOTA(0)-Tyr(3)-
  • Chromogranin A
  • Organometallic Compounds
  • Receptors, Somatostatin
  • Lutetium
  • Octreotide
Topics
  • Animals
  • Carcinoid Tumor (radiotherapy)
  • Chromogranin A (blood)
  • Humans
  • Intestinal Neoplasms (radiotherapy)
  • Lutetium (therapeutic use)
  • Mice
  • Mice, Nude
  • Octreotide (analogs & derivatives, therapeutic use)
  • Organometallic Compounds (therapeutic use)
  • Radiotherapy Dosage
  • Receptors, Somatostatin (metabolism)
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

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