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

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This invention relates to an improved mini-gastrin analogue designed for targeting tumors that express the CCK-2 receptor, such as medullary thyroid carcinomas and small cell lung cancers. The analogue features the substitution of methionine (which oxidizes easily and negatively affects clinical applications) with norleucine or another non-oxidizable amino acid. This modification provides a peptide with high tumor uptake and very low kidney accumulation when used for diagnostic imaging or therapy, especially when labeled with radioisotopes or linked to other diagnostic/therapeutic agents.

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• Radioisotope-based imaging of CCK-2 receptor positive tumors (e.g., PET or SPECT scans for medullary thyroid carcinoma, small cell lung cancer, or stromal ovarian tumors).
• Targeted radionuclide therapy for cancers expressing the CCK-2 receptor, improving precision and reducing side effects compared to conventional therapy.
• Targeted delivery of chemotherapeutic agents directly to CCK-2 receptor positive cancer cells, minimizing impact on healthy tissue.
• Optical imaging of tumors using analogues labeled with fluorescent or optically active compounds for surgical guidance or real-time monitoring.
• Use of nanoparticle/liposome carriers loaded with the peptide for multi-modal diagnostic or therapy purposes.

BenefitsContent extracted from patent full text and abstract with AI.

• Significantly higher tumor uptake and lower kidney accumulation, enabling safer and more effective diagnosis and therapy.
• Improved chemical stability due to the replacement of easily oxidized methionine, increasing robustness during manufacturing and storage.
• Enhanced tumor-to-kidney ratio reduces the risk of nephrotoxicity, a major limitation in existing peptide-based tumor targeting.
• Versatility in labeling: the peptide can be attached to a range of diagnostic and therapeutic agents (radioisotopes, fluorescent compounds, chemotherapeutics, nanoparticles), expanding its utility.
• Potential to detect and treat tumors that are negative to other receptor-targeted imaging agents, broadening clinical coverage.

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Inventors & Applicants

Patent Abstract

It is the objective of the present invention to provide a gastrin analogue which show high uptake in CCK-2 receptor positive tumours by simultaneously very low accumulation in the kidneys. This objective is achieved according to the present invention 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 stands for an amino acid replacing methionine and X stands for a chemical group attached to the peptide for the purpose of diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. In particular, very suitable compounds with respect to a high tumour to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidised easily which is a disadvantage for clinical application under GMP due to the forms which may occur. Therefore, the elimination of the methionine leads to a lower affinity to oxidation which in general favours the tumour-kidney-ratio. In a preferred embodiment of the present invention, the methionine is replaced by norleucine. This so-called PP-F11N mini gastrin exhibits currently the best tumour-kidney-ratio and is therefore the most promising candidate for clinical applications.