PSMA Imaging Conjugates With Lower Off-Target Tissue Uptake

Solution Overview

Problem

Existing PSMA-targeted cancer therapies and imaging modalities face challenges with significant accumulation and uptake in non-target tissues such as the liver, spleen, and salivary glands, leading to dose-limiting toxicity and interference in cancer imaging.

Innovation Solution

Development of PSMA-targeted conjugate compounds that minimize accumulation in non-target organs like the liver, and include a fluorophore and a metal chelating agent, which are linked to form a conjugate compound with a linker that binds to a fluorophore, and optionally a chelate with a metal, and are characterized by a selectivity for binding to a target, comprising a fluorophore and a metal chelate with a metal chelating agent, which are linked to form a conjugate compound with a metal nuclide, and optionally a fluorophore, where the fluorophore and metal chelating agent are independently selected to minimize uptake in non-PSMA expressing tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If PSMA-targeted compounds are used for cancer imaging and therapy, then tumor targeting efficacy is improved, but accumulation in non-target tissues such as salivary glands, liver, and spleen increases causing dose-limiting toxicity

Engineering Contradiction:

Improvetumor targeting efficacyVSAvoiddose-limiting toxicity in non-target tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by modifying specific regions of the PSMA-targeting molecule (the linker and payload regions) while maintaining the integrity of the PSMA-binding domain. This allows the molecule to retain high affinity for PSMA-expressing tumors while altering its interaction with non-target tissues, thereby reducing toxicity in organs like salivary glands, liver, and spleen without compromising tumor targeting efficacy

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs composite materials by creating conjugate compounds that combine PSMA-targeting moieties with therapeutic or imaging payloads through specially designed linkers. This composite structure enables selective accumulation in PSMA-positive tumors while minimizing off-target uptake, resolving the contradiction between effective tumor targeting and reduction of dose-limiting toxicity in normal tissues

Inventive Principle:

Principle #40Composite materials

2Measurement precision

If PSMA-targeted compounds are used for cancer imaging, then tumor detection capability is improved, but signal interference from non-cancer tissues expressing PSMA occurs

Engineering Contradiction:

Improvetumor detection capabilityVSAvoidimaging signal interference

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent applies local quality by modifying specific regions of the PSMA-targeting molecule (the linker and payload regions) while maintaining the integrity of the PSMA-binding domain. This allows the molecule to retain high affinity for PSMA-expressing tumors while altering its interaction with non-target tissues, thereby reducing toxicity in organs like salivary glands, liver, and spleen without compromising tumor targeting efficacy

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs composite materials by creating conjugate compounds that combine PSMA-targeting moieties with therapeutic or imaging payloads through specially designed linkers. This composite structure enables selective accumulation in PSMA-positive tumors while minimizing off-target uptake, resolving the contradiction between effective tumor targeting and reduction of dose-limiting toxicity in normal tissues

Inventive Principle:

Principle #40Composite materials

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 compounds demonstrate selective binding to PSMA-expressing cancer tissues, minimizing uptake in non-cancer tissues, enabling effective imaging and therapeutic interventions with reduced toxicity and interference.

Implementation Method 1

Y1 or Y2 includes a fluorophore

Methodology Applied

Scientific EffectFluorescence: Fluorescence

Implementation Method 2

one of Y1 or Y2 includes a metal chelating agent optionally complexed with a metal nuclide

Methodology Applied

Scientific EffectChelation:

Data Source

PatentUS20250387522A1PSMA targeted pet and fluorescence imaging compounds

Publication Date: 2025.12.25 CASE WESTERN RESERVE UNIV

AI summary

Multifunctional PSMA targeted conjugate compounds, pharmaceutical compositions comprising these compounds, use of the compounds for treating and detecting cancers in a subject are described herein.