Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment
A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2 , wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.
1. A pharmaceutical composition comprising a therapeutically effective amount of a mini-gastrin analogue having the formula:
X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2 ,
wherein Y is norleucine and X is a chemical group attached to the peptide for the purpose of therapeutic intervention at CCK-2 receptor associated diseases, and a pharmaceutically acceptable carrier.
2. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount is effective for treating CCK-2 receptor positive tumors.
3. The pharmaceutical composition of claim 2 , wherein the CCK-2 receptor positive tumor is selected from the group consisting of medullary thyroid carcinomas (MTC), small cell lung cancers (SCLC), astrocytomes and stromal ovarial tumors.
4. The pharmaceutical composition of claim 1 , wherein X is a chelator for radiometals complexed with a radionuclide.
5. The pharmaceutical composition of claim 4 , wherein the chelator for radiometals is DOTA.
6. The pharmaceutical composition of claim 4 , wherein the radionuclide is selected from the group consisting of 177 Lu, 90 Y and 111 In.
7. The pharmaceutical composition of claim 5 , wherein the mini-gastrin analogue is labelled with 177 Lu.
8. The pharmaceutical composition of claim 1 , wherein X is an optically active chemical compound.
9. The pharmaceutical composition of claim 1 , wherein X is a chemotherapeutic active compound.
10. The pharmaceutical composition of claim 1 , wherein X is a nanoparticle or liposome which has a therapeutic function by itself or which is loaded with an active compound.
11. The pharmaceutical composition of claim 10 , wherein X is a nanoparticle or liposome which is an optically active agent.
12. The pharmaceutical composition of claim 1 , which is formulated for i.v. injection.
13. The pharmaceutical composition of claim 7 , wherein the isotope:peptide ratio is 1:47.
14. The pharmaceutical composition of claim 5 , wherein the radionuclide is selected from the group consisting of 177 Lu, 90 Y and 111 In.