Mono- and Multi-Triazolominigastrins for Targeting of Cck2r-Positive Neoplasms

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention describes new derivatives of minigastrin, specifically mono- and multi-triazolominigastrins, designed for targeted detection and treatment of cancers that overexpress the cholecystokinin-2 receptor (CCK2R). By substituting certain peptide bonds with triazole groups and making other sequence modifications, these compounds achieve high receptor-specific internalization, excellent binding affinity to CCK2R, and improved plasma stability. They can be labeled with radioactive, optical, or therapeutic agents for use in imaging, therapy, or combination diagnostics and therapy.

Use CasesContent extracted from patent full text and abstract with AI.

• Targeted imaging (e.g., PET, SPECT) of CCK2R-positive tumors like medullary thyroid carcinoma, small cell lung cancer, and ovarian tumors.
• Peptide receptor radionuclide therapy (PRRT) for CCK2R-positive neoplasms using radiolabeled derivatives.
• Drug delivery of chemotherapeutic agents directly to CCK2R-expressing tumors.
• Fluorescent or optical imaging for intraoperative tumor localization or biopsy guidance.
• Theranostic applications by combining diagnostic and therapeutic labels in a single agent.
• Use of nanoparticles or liposomes conjugated with the minigastrin derivatives for enhanced delivery or combinatorial therapy.

BenefitsContent extracted from patent full text and abstract with AI.

• Greater specificity and uptake in CCK2R-expressing tumors, minimizing effects on healthy tissues.
• Improved biological stability and resistance to enzymatic degradation, leading to greater tumor retention and potential efficacy.
• Versatility – the compounds can deliver a range of agents (radionuclides, optical dyes, chemotherapeutics) for either diagnosis, therapy, or both (theranostics).
• Reduced risk of kidney toxicity due to improved molecular design and biodistribution.
• Potential for improved diagnostic sensitivity and therapeutic response in cancers not responsive to existing somatostatin-receptor–targeted agents.
• Adaptability to various imaging and therapeutic approaches (radioactive, optical, chemotherapeutic, nanoparticle-based).

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

It is the objective of the present invention to provide minigastrin derivates that have a high receptor specific cell internalization, excellent IC50 values towards the CCK2R and sufficient plasma stability.This objective is achieved according to the present invention by a minigastrin derivate, in particular mono- and multi-triazolominigastrins for targeting of CCK2R positive neoplasms, having the formula:X-Z-Ψ[Tz]-Ala-Ψ[Tz]-Tyr-Ψ[Tz]-Gly-Trp-Nle-Asp-Phe-NH2 (Y), orX-Z-DGlu-Ψ[Tz]-Ala-Tyr-Ψ[Tz]-Gly-Trp-Nle-Asp-Phe-NH2 (Y), orX-Z-DGlu-Ala-Tyr-Ψ[Tz]-Gly-Trp-Nle-Asp-Phe-NH2 (Y),while Ψ[Tz] stands for a 1,4-disubstituted or a 1,5-disubstituted 1,2,3-triazole, X stands for a chemical group attached to the peptide for the purpose of diagnostic and/or therapeutic intervention at CCK2R-relevant diseases, Y stands for C-terminal modifications of the peptide, such as amide, primary and secondary amides, free carboxylic acids and carboxylic ester derivatives including but not limited to amides and esters derived from linear or branched alkyl-, alkenyl-, alkynyl- aromatic-, and heterocyclic alcohols, and Z stands for a linker or DGlu* wherein DGlu* stands for a chain of DGlu having 1 to 6 repetitions (-DGlu- to -DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-).These minigastrin derivates have specifically a high receptor specific cell internalization, excellent IC50 values towards the CCK2R and sufficient plasma stability.