Induction of Human Somatostatin Receptor Subtype 2 on Breast Tumors with an Adenoviral Vector for Their Treatment and Detection with a Radiolabeled Peptide

摘要

Targeted radiation therapy for breast cancer is a rational approach, however; there are problems associated with low receptor expression on tumors and bone marrow toxicity due to the long serum half-life of antibodies used to target the radiation. An adenoviral vector encoding the human somatostatin receptor subtype 2 (AdSSTr2) has been produced. The MDA- MB-468 and BT-474 human breast cancer cells were infected with AdSSTr2 and harvested 48 h later for membrane preparations. Membrane SSTr2 expression was determined by a competitive binding assay using iodine-l25 (1-125)-labeled somatostatin. Localization of Tc- 99m-P2O45 (a high affinity somatostatin analogue) in mice bearing subcutaneous tumors was evaluated by injecting AdSSTr2 i.v. followed by an i.v. injection of Tc-99m-P2O45 48 h later. Localization of Tc-99m-P2O45 was determined by counting tissues in a gamma counter. These studies provide the proof-of-principle that this novel paradigm can be used to treat and detect breast cancer.