Functionalizable PSMA Ligand Precursors for Multimodal Imaging
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Solution Overview
Problem
Current PSMA ligands are limited in their functionality, lacking the ability to be derivatized for multiple imaging and therapeutic modalities, and they struggle to achieve complete resection of prostate tumors and detect metastatic lymph nodes during surgery, leading to potential recurrence and poor patient outcomes.
Innovation Solution
Development of a precursor compound with a positively charged amine for further derivatization, allowing attachment of chelators, labels, and linkers, enabling multimodal imaging and therapy, including photodynamic therapy and radiodetection of metastases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If current PSMA ligands are used for imaging and therapy, then diagnostic and treatment functions are provided, but the ligands cannot be derivatized for multiple modalities and require multiple tracer injections
Solution Approach 1:
The patent applies universality by designing a single PSMA-targeting ligand platform that can be derivatized with multiple different functional groups (chelators, fluorophores, photosensitizers, radiolabels) to perform multiple functions including SPECT/CT imaging, PET imaging, fluorescence imaging, and photodynamic therapy, eliminating the need for multiple separate tracer injections
2Reliability
If surgeons attempt complete oncological resection, then tumor removal is improved, but nerve damage occurs causing functional side effects
Solution Approach 1:
The patent applies color changes by incorporating fluorophores (such as IRDye700DX) into the PSMA-targeting ligand, enabling intraoperative fluorescence imaging that causes tumor tissue to emit visible light signals, allowing surgeons to clearly distinguish tumor margins from healthy nerve tissue and achieve complete resection while preserving nerves
3Ease of operation
If anatomical landmarks are used for lymph node detection, then surgical guidance is provided, but detection accuracy is reduced due to tissue shifts and atypical locations
Solution Approach 1:
The patent applies the intermediary principle by using PSMA-targeting ligands conjugated with imaging agents as a mediator that specifically binds to PSMA-expressing lymph nodes, providing a molecular-level guidance system that overrides anatomical landmark limitations and enables accurate detection of lymph nodes regardless of tissue shifts or atypical locations
4Reliability
If small tumor lesions are present, then cancer survival rate is improved, but detection by intraoperative imaging becomes difficult
Solution Approach 1:
The patent applies color changes by using fluorophores conjugated to PSMA-targeting ligands that accumulate in small tumor lesions, causing even microscopic tumors to emit strong fluorescence signals that are easily detectable by intraoperative fluorescence imaging systems, enabling detection and resection of small lesions that would be invisible with conventional imaging
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 compound enables complete resection of tumors and accurate detection of lymph nodes with minimal side effects, enhancing surgical outcomes by providing a single tracer for both imaging and therapy, thus reducing recurrence and improving patient prognosis.
Implementation Method 1
tPDT is a highly selective cancer treatment based on targeting molecules conjugated to photosensitizers that, after exposure to near infrared light, transform oxygen into radical oxygen species (ROS) toxic for the tumor cell
Implementation Method 2
The simultaneously present chelator renders the compound suitable for preoperative SPECT/CT imaging and radiodetection of metastatic lymph nodes
Data Source
AI summary
The invention relates to a new class of compounds that can serve as prostate specific membrane antigen (PSMA) ligands, and to precursors to this class. The precursors have an amine that is available for functionalisation. Derivatives of the compounds are useful for imaging and therapy of cancer.