Spatial quantification of biomarkers within target tissues with image analysis platform

 

Exploring tissue-based biomarkers is a crucial component of pre-clinical/clinical drug development, as it can help identify new therapeutic targets, evaluate surrogate markers of drug effectiveness, and predict potential benefits of a candidate compound.

Using image analysis allows us to evaluate tissue biomarkers in greater detail and study cellular interactions in complex biological processes. Our digital pathology data analysis workflow allows the automation of cell segmentation and their classification to resolve the molecular architecture of the tissue.

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Cell deconvolution to estimate cell type abundance from spatial transcriptomic data within heterogeneous tissues

 

Central to spatial biology is the mapping of cell types across heterogenous tissues. This process helps us understand the relationship between cells in the context of disease and their role in response to treatment. Based on cell abundances, we identified different microenvironment cell subtypes within non-small-cell lung cancer (NSCLC) tissues and differentiated how they responded to checkpoint inhibitor therapy.

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Assessment of reproducibility in multiplex immunohistochemistry

 

Multiplex Immunohistochemistry (mlHC) is an advanced technique that can detect tissue-based biomarkers simultaneously, which transforms the traditional approach of immunohistochemistry. mlHC enables precision medicine in both research and clinical practice because it evaluates various proteins and their spatial distribution within single tissue sections at a cellular level.  

Specific requirements are crucial for achieving high-quality staining and analysis, and to deem a mlHC assay as validated, it must be proven to be analytically reproducible.

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An automated complementary method for spatially resolved quantitative analysis of drugs and biomarkers

 

Having an initial understanding of drug distribution, quantification and target engagement within disease-relevant histological structures is critical in choosing more effective drug candidates. MALDI MSI unveils the quantitative distribution of label-free drugs, or biomarkers, providing valuable data that complements information obtained through traditional approaches. 
 
Our optimized workflows offer solutions to problems that are sometimes encountered when you quantify drugs and biomarkers with MSI, and open the door for precision quantification of any molecule in specific regions of interest. 
 
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Discover the intricacies of molecular landscapes through quantitative mass spectrometry imaging (QMSI)

 

Aliri’s proprietary imaging workflows will help you understand localization, quantification, and distribution of drugs at the site of action.  

Studying drug efficacy at the site of action gives us valuable and unique insights into:

  • Drug bioavailability   
  • Drug biodistribution  
  • Targeted tissue exposure   
  • On-tissue PK/PD  
  • Monitoring the drug effects through readout biomarkers (metabolites, lipids, genes expression, proteins)  

Our QMSI spatial platform uses data analysis to conduct molecular distributions, and artificial intelligence to find patterns and make predictions. This advanced imaging technique allows you to visualize the molecule within tissues, and evaluate how prevalent the drug is within the histological region of interest.

Our high expertise in this area sets us apart from other CROs in pharma/bio industries and positions us as a leader in spatial bioanalysis and biology services.

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WRIB 2023 Poster: Bimiralizib distribution in human skin biopsies after topical administration obtained by validated quantitative mass spectrometry imaging

 

Quantitative MALDI Mass Spectrometry Imaging (QSMI) can be used to determine drug distribution in first-in-human studies

At WRIB 2023, Shane Karnik, Senior Laboratory Director at Aliri, presented a poster about utilizing QSMI to determine Bimiralizib distribution in human skin biopsies.

Recent clinical trial results validate Bimiralizib distribution in human skin and showcase:

  • Robustness of MALDI MSI method 
  • Approach not limited to dermatology; already applied in oncology
  • Absolute quantification allowed to determine if the compound reached the site of action  
  • Method allows to characterize small compound PK in clinical trial
  • Method allows the characterization of the target engagement 

 

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ATP detection by quantitative mass spec imaging (QMSI)

 

As leaders in the field of spatial bioanalysis, Aliri utilizes state-of-the-art imaging techniques to evaluate localization and distribution of molecules within tissue microenvironments. 

 

Our unique approach utilizing by quantitative mass spectrometry imaging (QMSI) for pathway detection allows us to:

  • Stabilize the ATP pathway with an inhibitor cocktail
  • Normalize the signal intensities from the raw data sets 
  • Perform the absolute quantification of the ATP
  • Calculate the relative quantification of the ADP and AMP  


Learn how we can help you leverage ATP pathway detection with QMSI

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Batch alignment of mass spectrometry imaging (MSI) metabolome through data integration

 

Mass spectrometry imaging (MSI) is a critical tool used to investigate tissues and molecules in spatial bioanalysis. Technical challenges in MSI, also known as batch-effects, have proven to impede reliable comparison of data from large-scale studies performed in translational clinical research. 

Meaningful analysis of data generated in large-scale studies is critical for medicine and biology studies. This application note focuses on a batch correction method designed to minimize impedance of batch-effects and allow reliable identification of biological clusters and their comparison.  
 
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Automated approach to quantify single molecule in complex tissues

This application note focuses on an efficient analysis method which enables the quantification of molecules at the single-cell level. Accurate RNA quantification in single molecules is crucial to understand the dynamics of gene expression and regulation. 
 
In this study, individual molecules were imaged in fixed cells and DNA staining was performed in tumoral areas of the tissue. Analysis results showcase quantification of single cells and provide an understanding of cell-to-cell interactions in cancer cells and other molecules.  
 
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QMSI vs. QWBA: Evaluating Benefits and Risks

Knowing when to use Quantitative Mass Spectrometry Imaging (QMSI) instead of Quantitative Whole-Body Autoradiography (QWBA) can make or break a timeline and budget for pharma and biotech companies.

Consider the following key advantages when selecting which technique is right for your drug development program:

QSMI Advantages:

  • Label-free quantification of thousands of analytes
  • Excellent differentiation among parent drugs, metabolites, and other substances
  • Highly specific in quantification by location in tissue

QWBA Advantages:

  • Highly precise quantification capabilities, even at low and high limits of detection
  • Spatial resolution at the cellular level
  • Gold standard technique for the late-stage regulatory distribution studies

Even though QWBA remains the gold standard technique during late stage for regulatory agencies, QMSI is frequently used in support of the autoradiography in certain circumstances.

Further evaluate the benefits and risks associated with each technology.

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