Radiolabelled Bradykinin B1R Targeting Compounds for Cancer Imaging
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Solution Overview
Problem
Current imaging techniques for bradykinin B1 receptors face challenges such as high nonspecific binding and rapid clearance, which hinder effective visualization and diagnosis of tissues or tumors expressing these receptors, particularly in cancer and inflammatory conditions.
Innovation Solution
Development of radio-labelled bradykinin B1 receptor targeting compounds with specific peptidic or non-peptidic structures that selectively bind to B1R, incorporating radiolabels like 99mTc, 18F, 123I, or 111In for PET and SPECT imaging, allowing for precise imaging and potential therapeutic applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional imaging probes are used for B1R imaging, then receptor binding occurs, but high nonspecific binding and rapid clearance prevent effective visualization
Solution Approach 1:
The patent modifies the chemical structure of bradykinin analogues by changing amino acid residues (e.g., replacing Phe8 with D-Phe, Phe11 with D-Phe or other residues) to alter binding characteristics. These structural parameter changes reduce nonspecific binding while maintaining B1R affinity, and modify pharmacokinetic properties to slow clearance rates, enabling effective imaging visualization
Solution Approach 2:
The patent creates composite imaging probes by conjugating radiolabels (e.g., 125I, 111In, 68Ga) to modified bradykinin B1R-targeting peptides. This composite structure combines the receptor-targeting capability of the peptide with the imaging functionality of the radiolabel, while the modified peptide structure reduces nonspecific binding and optimizes clearance characteristics for effective imaging
2Illumination intensity
If high quantities of imaging probes are used to overcome rapid clearance, then signal strength increases, but receptor saturation occurs
Solution Approach 1:
The patent modifies the pharmacokinetic parameters of the imaging probes through structural modifications of the bradykinin analogue. These changes slow the clearance rate, allowing sufficient imaging signal to be achieved with lower administered quantities, thereby avoiding receptor saturation while maintaining adequate signal strength for visualization
Solution Approach 2:
The patent uses low quantities of high-specific-activity radiolabelled probes, which is insufficient to saturate receptors but adequate for imaging when combined with the slowed clearance rate. This partial action approach achieves the desired imaging signal without the harmful effect of receptor saturation
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
These compounds demonstrate high contrast, rapid renal clearance, and minimal non-target uptake, enabling effective diagnostic imaging and potential therapeutic targeting of B1R-expressing tissues or tumors, including breast, prostate, lung, and brain cancers.
Implementation Method 1
a radiolabel suitable for in vivo imaging or radiotherapy
Implementation Method 2
positron emission tomography (PET)
Implementation Method 3
single-photon emission computed tomography (SPECT)
Implementation Method 4
a radiometal chelating agent chelating a radioisotope
Implementation Method 5
compounds that selectively bind to B1R
Implementation Method 6
clearance rates that are sufficiently slow to allow for uptake at the target site(s) but rapid enough to allow the uptake to be visualized
Data Source
Figure 1
Figure 2A~2B
Figure 2C
AI summary
Bradykinin B1 receptor (B1R) targeting peptides and compounds are radiolabelled with radioisotopes that are suitable for imaging and/or radiotherapy. Said radiolabelled peptides and compounds have utility in imaging tissues expressing or overexpressing B1R and/or treating diseases or conditions in which B1R is expressed or overexpressed, including cancer.