Bivalent PSMA-GRPR Ligands for Prostate Cancer Imaging

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Solution Overview

Problem

Current methods for detecting and treating prostate cancer are inadequate, particularly for early detection and metastatic disease, with existing therapies having significant side effects and limited effectiveness, and there is a need for improved diagnostic techniques to accurately stage and treat prostate cancer.

Innovation Solution

Development of bivalent binding agents, specifically [DUPA-6-Ahx-Lys(M-DOTA)-X-RM2], which target prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR), allowing for imaging and diagnosis of prostate cancer using PET and SPECT techniques, and potentially offering therapeutic options with radionuclides like 177Lu and 90Y.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatment methods (radiation therapy, chemotherapy, surgery) are used for prostate cancer, then treatment can be provided, but side effects increase and effectiveness against metastatic disease decreases

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The treatment approach is segmented into two distinct phases: diagnostic imaging phase using radiolabeled agents (68Ga, 64Cu) to detect and stage prostate cancer, followed by therapeutic phase using different radionuclides (177Lu, 90Y) to treat confirmed tumors. This segmentation allows optimization of each phase independently, improving overall effectiveness while reducing unnecessary exposure to harmful therapies.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention changes the parameter of radionuclide selection based on the treatment stage and target characteristics. Diagnostic stages use isotopes with appropriate half-lives and emission types for imaging (68Ga, 64Cu), while therapeutic stages use isotopes optimized for tumor cell destruction (177Lu, 90Y). This parameter optimization improves treatment effectiveness while minimizing harmful effects through precise dosing and targeting.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If early detection methods are used to improve diagnostic accuracy, then detection precision improves, but current methods remain insufficient for accurate early diagnosis

Engineering Contradiction:

Improvediagnostic accuracyVSAvoidearly detection capability

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The binding agents are designed with multi-functionality, serving both diagnostic and therapeutic purposes through the same molecular target (PSMA or GRPR). The same ligand structure can be labeled with different radionuclides for either imaging or therapy, ensuring high reliability in early detection while maintaining diagnostic accuracy through consistent target recognition.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention uses composite structures combining organic ligands (DUPA, RM2 peptides) with inorganic radionuclides (Ga, Cu, Lu, Y isotopes). This composite approach leverages the high specificity of organic molecules for PSMA/GRPR targets while utilizing the detectable or therapeutic properties of radionuclides, achieving both high diagnostic accuracy and reliable early detection capability.

Inventive Principle:

Principle #40Composite materials

3Quantity of substance

If bivalent binding agents targeting both PSMA and GRPR are used, then tumor uptake increases, but agent complexity increases

Engineering Contradiction:

Improvetumor uptakeVSAvoidagent structure

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The invention merges two separate targeting functions into a single bivalent agent by combining PSMA-targeting moieties (DUPA) with GRPR-targeting moieties (RM2 peptides) through linker chemistry. This merging achieves enhanced tumor uptake through dual-receptor engagement while managing structural complexity through modular design, where each functional domain retains its independence but contributes to overall targeting efficacy.

Inventive Principle:

Principle #5Merging (Combining)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The bivalent binding agents demonstrate high affinity and specificity for PSMA/GRPR, enabling effective imaging and potential therapeutic interventions with improved tumor uptake and reduced side effects, enhancing diagnostic accuracy and treatment options for prostate cancer.

Implementation Method 1

The bivalent binding agents demonstrate high affinity and specificity for PSMA/GRPR

Methodology Applied

Scientific EffectAffinity binding:

Implementation Method 2

allowing for imaging and diagnosis of prostate cancer using PET and SPECT techniques

Methodology Applied

Scientific EffectRadioactive decay: Radioactive Decay

Data Source

PatentUS11167048B2Dual targeting ligand for cancer diagnosis and treatment

Publication Date: 2021.11.09 THE CURATORS OF THE UNIVERSITY OF MISSOURI

AI summary

Disclosed are compositions and methods relating to prostate cancer. In particular, disclosed are bivalent targeting ligands that specifically bind prostate specific membrane antigen and gastrin-releasing peptide receptor. Bivalent binding agents disclosed herein can be used to image a tissue in a subject in need thereof and to diagnose prostate cancer in a subject in need thereof. Bivalent binding agents disclosed herein can be used to treat prostate cancer in a subject in need thereof.