Antitumor and antiangiogenic effects of somatostatin receptor-targeted in situ radiation with (111)In-DTPA-JIC 2DL

The Journal of Surgical Research
S A GulecE A Woltering

Abstract

Expression of somatostatin receptor subtype 2 (sst 2) in angiogenic tumor vessels appears to be homogeneous, while tumor cell expression of this receptor is often heterogeneous. We have developed a novel in vitro three-dimensional tumor angiogenesis model to study the antitumor and the antiangiogenic effects of radiolabeled somatostatin analogs. We hypothesized that targeted in situ radiation with an Auger electron-emitting radiolabeled somatostatin analog would produce receptor-specific cytotoxicity in sst 2-expressing cells. IMR-32 human neuroblastoma (sst 2-positive) and MDA MB-231 human breast cancer (sst 2-negative) xenografts were created in nude mice from monolayer cell cultures. Fragments of these tumors were embedded in three-dimensional fibrin gels supplemented with endothelial growth media and incubated for a period of 14 days. Tumor fragments were treated with 50 microCi/ml of (111)In-JIC 2DL, a sst 2-preferring somatostatin analog, or medium on Day 1. Initial angiogenic activity was determined at 48 h and the mean angiogenic score and tumoricidal responses were assessed on Day 14. Tumoricidal effects of (111)In-JIC 2DL were seen only in sst 2-positive IMR-32 tumors. However, the angiogenic response was inhibited in...Continue Reading

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Citations

May 28, 2002·Journal of Endocrinological Investigation·R Deghenghi
Sep 25, 2003·Cancer Biotherapy & Radiopharmaceuticals·Eugene A Woltering
Nov 26, 2010·Endocrinology and Metabolism Clinics of North America·John LyonsEugene A Woltering
Apr 11, 2006·The Journal of Surgical Research·James M LewisEugene A Woltering
Jul 21, 2005·Technology in Cancer Research & Treatment·T RobsonD G Hirst
Jan 15, 2005·Journal of Receptor and Signal Transduction Research·Alex N EberleSylvie Froidevaux
Aug 30, 2007·Journal of Surgical Oncology·Seza A Gulec, Richard Baum
Jun 2, 2007·Pharmacological Reviews·Domenico RibattiGastone G Nussdorfer
Oct 2, 2002·Clinical Endocrinology·N García de la TorreH E Turner
Dec 31, 2003·Annals of Surgical Oncology·Seza A Gulec, Eugene A Woltering
Oct 18, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jean R StarkeyCharles W Spangler

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