GOT1 xenografted to nude mice: a unique model for in vivo studies on SSTR-mediated radiation therapy of carcinoid tumors.
Malignant carcinoid tumors express high numbers of somatostatin receptors. Radiation therapy using labeled somatostatin analogs is a novel treatment modality for these tumors. We have analyzed the biokinetics and therapeutic effect of radiolabeled somatostatin analog on a human midgut carcinoid grafted to nude mice. A transplantable human midgut carcinoid (GOT1) was grafted to the back of nude mice. Tumor-bearing mice were injected with (111)In-DTPA-D-Phe(1)-octreotide, followed by measurement of (111)In activity concentration ratios in tumor tissues. Tumor-bearing mice were also injected with (177)Lu-DOTA-Tyr(3)-octreotate and followed for 7 days. The concentration of (111)In-DTPA-D-Phe(1)-octreotide in tumor tissues was very high 4 hours postinjection with 0.4-13% of injected activity per gram. Injection of 30-120 MBq (177)Lu-DOTA-Tyr(3)-octreotate reduced tumor volume to 7-14% of the original tumor volume 7 days postinjection. Microscopic analysis of treated tumors revealed widespread areas of tumor cell necrosis and fibrosis. It was found that grafted GOT1 cells to nude mice represent an authentic model for studying human midgut carcinoids. Radiolabeled somatostatin analogs have a high selectivity for tumor tissue and can induce tumor cell necrosis. Radiotherapy of carcinoid tumors with (177)Lu-DOTA-Tyr(3)-octreotate appears to be a promising treatment modality for either palliative treatment or completion therapy after attempted surgical cure.
Nilsson
Ola
O
Lundberg Laboratory for Cancer Research at the Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden. ola.nilsson@llcr.med.gu.se
Kölby
Lars
L
Bernhardt
Peter
P
Forssell-Aronsson
Eva
E
Johanson
Viktor
V
Ahlman
Håkan
H
D000818:Animals; D002276:Carcinoid Tumor / Q000378:metabolism / Q000532:radiotherapy*; D004195:Disease Models, Animal; D007205:Indium Radioisotopes / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015282:Octreotide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D007205:Indium Radioisotopes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C071632:SDZ 215-811; D004369:Pentetic Acid; C447941:lutetium Lu 177 dotatate; D015282:Octreotide