AGONIST-DEPENDENT INTERNALIZATION OF HUMAN SOMATOSTATIN RECEPTORS TYPES 1-5

摘要

The present invention relates to the uses of human somatostatin receptors types 1-5 in the diagnosis and/or treatment of diseases and more particularly to tumor cells, e.g. breast cancer and in cases of Alzheimer's. The present invention relates to (i) recombinant host cells (CHO-Kl cells) individually expressing the 5 hSSTR subtypes; (ii) the use of these cells as tools for testing the ability of synthetic SST agonists or antagonists to induce receptor internalization or upregulation; (iii) the use of the internalization property of hSSTR subtypes to target tumors for selective targeted destruction. For instance, subtypes such as hSSTR3 and 5 which are extensively internalized could be targeted with selective α or β-emitting SST radioligands for radiotherapy of, for example, breast cancers which display a rich concentration of these receptors; (iv) the use of the ability of hSSTR1 (in particular) and hSSTR2 and 4 (to a lesser extent) to be upregulated at the cell surface upon prolonged treatment with agonist as a test for increasing the sensitivity of receptor scans for detection and diagnosis of tumors and inflammatory conditions; (v) the use of the differential ability of the hSSTR subtypes to be upregulated or internalized as a means for producing enhanced images in receptor scans by subtraction analysis to recruit, for example, SSTR1 selective to the membrane whilst internalizing others such as hSSTR3, hSSTR4, and hSSTR5.