Visualization of the distribution of nanoparticle-formulated AZD2811 in mouse tumor model using matrix-assisted laser desorption ionization mass spectrometry imaging

Abstract Penetration of nanoparticles into viable tumor regions is essential for an effective response. Mass spectrometry imaging (MSI) is a novel method for evaluating the intratumoral pharmacokinetics (PK) of a drug in terms of spatial distribution. The application of MSI for analysis of nanomedicine PK remains in its infancy. In this study, we evaluated the applicability of MALDI-MSI for nanoparticle-formulated drug visualization in tumors and biopsies, with an aim toward future application in clinical nanomedicine research. We established an analytic method for the free drug (AZD2811) and then applied it to visualize nanoparticle-formulated AZD2811. MSI analysis demonstrated heterogeneous intratumoral drug distribution in three xenograft tumors. The intensity of MSI signals correlated well with total drug concentration in tumors, indicating that drug distribution can be monitored quantitatively. Analysis of tumor biopsies indicated that MSI is applicable for analyzing the distribution of nanoparticle-formulated drugs in tumor biopsies, suggesting clinical applicability.

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Mapping of drug distribution in the rabbit liver tumor model by complementary fluorescence and mass spectrometry imaging

Journal of Controlled Release ◽

10.1016/j.jconrel.2017.10.042 ◽

2018 ◽

Vol 269 ◽

pp. 128-135 ◽

Cited By ~ 6

Author(s):

Katrin Fuchs ◽

Andras Kiss ◽

Pierre E. Bize ◽

Rafael Duran ◽

Alban Denys ◽

...

Keyword(s):

Mass Spectrometry ◽

Liver Tumor ◽

Mass Spectrometry Imaging ◽

Drug Distribution ◽

Tumor Model ◽

Rabbit Liver

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Revealing chemical evidence from fingerprints through matrix-assisted laser desorption/ionization - mass spectrometry imaging

10.31274/etd-20200624-58 ◽

2020 ◽

Author(s):

Paige Lauren Hinners

Keyword(s):

Mass Spectrometry ◽

Mass Spectrometry Imaging ◽

Laser Desorption ◽

Ionization Mass Spectrometry ◽

Ionization Mass ◽

Laser Desorption Ionization ◽

Desorption Ionization ◽

Matrix Assisted Laser ◽

Matrix Assisted Laser Desorption ◽

Chemical Evidence

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Sample preparation strategy for the detection of steroid-like compounds using MALDI mass spectrometry imaging: pulmonary distribution of budesonide as a case study

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-021-03393-6 ◽

2021 ◽

Author(s):

Riccardo Zecchi ◽

Pietro Franceschi ◽

Laura Tigli ◽

Davide Amidani ◽

Chiara Catozzi ◽

...

Keyword(s):

Mass Spectrometry ◽

Sample Preparation ◽

Mass Spectrometry Imaging ◽

Maldi Mass Spectrometry ◽

Adult Rabbit ◽

Chronic Obstructive ◽

Ionization Mass ◽

Obstructive Pulmonary Disease ◽

Imaging Protocol ◽

Girard’S Reagent

AbstractCorticosteroids as budesonide can be effective in reducing topic inflammation processes in different organs. Therapeutic use of budesonide in respiratory diseases, like asthma, chronic obstructive pulmonary disease, and allergic rhinitis is well known. However, the pulmonary distribution of budesonide is not well understood, mainly due to the difficulties in tracing the molecule in lung samples without the addition of a label. In this paper, we present a matrix-assisted laser desorption/ionization mass spectrometry imaging protocol that can be used to visualize the pulmonary distribution of budesonide administered to a surfactant-depleted adult rabbit. Considering that budesonide is not easily ionized by MALDI, we developed an on-tissue derivatization method with Girard’s reagent P followed by ferulic acid deposition as MALDI matrix. Interestingly, this sample preparation protocol results as a very effective strategy to raise the sensitivity towards not only budesonide but also other corticosteroids, allowing us to track its distribution and quantify the drug inside lung samples. Graphical abstract

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Diagnosis of Agglomeration and Crystallinity of Active Pharmaceutical Ingredients in Over the Counter Headache Medication by Electrospray Laser Desorption Ionization Mass Spectrometry Imaging

Molecules ◽

10.3390/molecules26030610 ◽

2021 ◽

Vol 26 (3) ◽

pp. 610

Author(s):

Mariann Inga Van Meter ◽

Salah M. Khan ◽

Brynne V. Taulbee-Cotton ◽

Nathan H. Dimmitt ◽

Nathan D. Hubbard ◽

...

Keyword(s):

Mass Spectrometry ◽

Mass Spectrometry Imaging ◽

Laser Desorption ◽

Ionization Mass Spectrometry ◽

Ionization Mass ◽

Active Pharmaceutical Ingredients ◽

Laser Desorption Ionization ◽

Over The Counter ◽

Pharmaceutical Ingredients ◽

Desorption Ionization

Agglomeration of active pharmaceutical ingredients (API) in tablets can lead to decreased bioavailability in some enabling formulations. In a previous study, we determined that crystalline APIs can be detected as agglomeration in tablets formulated with amorphous acetaminophen tablets. Multiple method advancements are presented to better resolve agglomeration caused by crystallinity in standard tablets. In this study, we also evaluate three “budget” over-the-counter headache medications (subsequently labeled as brands A, B, and C) for agglomeration of the three APIs in the formulation: Acetaminophen, aspirin, and caffeine. Electrospray laser desorption ionization mass spectrometry imaging (ELDI-MSI) was used to diagnose agglomeration in the tablets by creating molecular images and observing the spatial distributions of the APIs. Brand A had virtually no agglomeration or clustering of the active ingredients. Brand B had extensive clustering of aspirin and caffeine, but acetaminophen was observed in near equal abundance across the tablet. Brand C also had extensive clustering of aspirin and caffeine, and minor clustering of acetaminophen. These results show that agglomeration with active ingredients in over-the-counter tablets can be simultaneously detected using ELDI-MS imaging.

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Desorption Electrospray Ionization Mass Spectrometry Imaging of Cimbi-36, a 5-HT2A Receptor Agonist, with Direct Comparison to Autoradiography and Positron Emission Tomography

Molecular Imaging and Biology ◽

10.1007/s11307-021-01592-2 ◽

2021 ◽

Author(s):

Sophie C. Jacobsen ◽

Nikolaj R. Speth ◽

Mengfei Xiong ◽

Matthias M. Herth ◽

Jesper L. Kristensen ◽

...

Keyword(s):

Mass Spectrometry ◽

Positron Emission Tomography ◽

Electrospray Ionization ◽

Electrospray Ionization Mass Spectrometry ◽

Receptor Agonist ◽

Mass Spectrometry Imaging ◽

Desorption Electrospray Ionization ◽

Emission Tomography ◽

Ionization Mass ◽

Positron Emission

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Discovery of Spatial Peptide Signatures for Neuroblastoma Risk Assessment by MALDI Mass Spectrometry Imaging

Cancers ◽

10.3390/cancers13133184 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3184

Author(s):

Zhiyang Wu ◽

Patrick Hundsdoerfer ◽

Johannes H. Schulte ◽

Kathy Astrahantseff ◽

Senguel Boral ◽

...

Keyword(s):

Mass Spectrometry ◽

Risk Assessment ◽

Mass Spectrometry Imaging ◽

Principal Component ◽

Therapy Resistance ◽

Risk Classification ◽

Intratumor Heterogeneity ◽

Ionization Mass ◽

Characteristic Analysis ◽

Analytical Strategy

Risk classification plays a crucial role in clinical management and therapy decisions in children with neuroblastoma. Risk assessment is currently based on patient criteria and molecular factors in single tumor biopsies at diagnosis. Growing evidence of extensive neuroblastoma intratumor heterogeneity drives the need for novel diagnostics to assess molecular profiles more comprehensively in spatial resolution to better predict risk for tumor progression and therapy resistance. We present a pilot study investigating the feasibility and potential of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to identify spatial peptide heterogeneity in neuroblastoma tissues of divergent current risk classification: high versus low/intermediate risk. Univariate (receiver operating characteristic analysis) and multivariate (segmentation, principal component analysis) statistical strategies identified spatially discriminative risk-associated MALDI-based peptide signatures. The AHNAK nucleoprotein and collapsin response mediator protein 1 (CRMP1) were identified as proteins associated with these peptide signatures, and their differential expression in the neuroblastomas of divergent risk was immunohistochemically validated. This proof-of-concept study demonstrates that MALDI-MSI combined with univariate and multivariate analysis strategies can identify spatially discriminative risk-associated peptide signatures in neuroblastoma tissues. These results suggest a promising new analytical strategy improving risk classification and providing new biological insights into neuroblastoma intratumor heterogeneity.

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