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GOT1 Xenografted to Nude Mice: A Unique Model for in Vivo Studies on SSTR‐Mediated Radiation Therapy of Carcinoid Tumors
Author(s) -
NILSSON OLA,
KÖLBY LARS,
BERNHARDT PETER,
FORSSELLARONSSON EVA,
JOHANSON VIKTOR,
AHLMAN HÅKAN
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1294.031
Subject(s) - somatostatin , somatostatin receptor , in vivo , octreotide , radionuclide therapy , carcinoid tumors , radiation therapy , neuroendocrine tumors , nude mouse , cancer research , pathology , necrosis , medicine , chemistry , cancer , nuclear medicine , biology , microbiology and biotechnology
A bstract : 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.