CCK2 / - MINI-GASTRIN ANALOGUE IN PARTICULAR FOR USE IN CCK2 RECEPTOR POSITIVE TUMOUR DIAGNOSIS AND/OR TREATMENT

摘要

It is an object of the present invention to provide a gastrin analog exhibiting high uptake by very low intracellular accumulation in CCK-2 receptor positive tumors at the same time. This object is according to the invention, the formula: has an X-DGlu-DGlu-DGlu- DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2, where Y is to replace the methionine Amino acid and X is achieved by the small-gastrin analog of PP-F11, which represents a chemical group attached to the peptide for the purpose of diagnostic and / or therapeutic intervention for CCK-2 receptor related diseases. In particular, a highly suitable compound in terms of high tumor to kidney ratio is a small-gastrin analog with six D-glutamic acid or six glutamine. These compounds are readily oxidizable and still retain methionine, a disadvantage to clinical applications under GMP due to the possible forms. Thus, the removal of methionine generally leads to a low oxidation affinity that favor tumor-kidney ratio. In a preferred embodiment of the present invention, methionine is substituted with norleucine. The so-called PP-F11N small-sized gastrin now represents the best tumor-kidney ratio and is therefore the most promising candidate for clinical applications.