Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment

Patent metadata

Field	Value
Publication number	US-10130724-B2
Application number	US-201415034943-A
Country	US
Kind code	B2
Filing date	Oct 23, 2014
Priority date	Nov 6, 2013
Publication date	Nov 20, 2018
Grant date	Nov 20, 2018

Abstract

A gastrin analog 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 analog 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 analogs 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.

First claim

The invention claimed is:

1. 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 norleucine and X is a chemical group attached to the peptide for the purpose of diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases.

2. The mini-gastrin analogue PP-F11 according to claim 1 , wherein X is a chelator for radiometals complexed with a radionuclide.

3. The mini-gastrin analogue PP-F11 according to claim 2 wherein the chelator for radiometals is DOTA.

4. The mini-gastrin analogue PP-F11 according to claim 2 , wherein the radionuclide is selected from the group consisting of 177 Lu, 90 Y and 111 In.

5. The mini-gastrin analogue PP-F11 according to claim 3 , wherein the DOTA-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH 2 is labelled with 177 Lu.

6. The mini-gastrin analogue PP-F11 according to claim 1 , wherein X is an optically active chemical compound.

7. The mini-gastrin analogue PP-F11 according to claim 1 , wherein X is a chemotherapeutic active compound.

8. The mini-gastrin analogue PP-F11 according to claim 1 , wherein X is a nanoparticle or liposome which has a diagnostic function or therapeutic function by themselves or which is loaded with an active compound.

9. The mini-gastrin analogue PP-F11 according to claim 8 , wherein X is a nanoparticle or liposome which is selected from the group consisting of an optically active agent and an MRI contrast agent.

Assignees

• Scherrer Inst Paul

Inventors

• Behe Martin
• Schibli Roger

Classifications

• A61K51/08

  Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins} · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P13/12

  of the kidneys · CPC title