ArticleJournal of visualized experiments : JoVE2018
Spatial Quantification of Drugs in Pulmonary Tuberculosis Lesions by Laser Capture Microdissection Liquid Chromatography Mass Spectrometry (LCM-LC/MS).
Article in Journal of visualized experiments : JoVE, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 3 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Studying intrapulmonary pharmacokinetics for tuberculosis treatment: a systematic review of methodology.The Journal of antimicrobial chemotherapy · 2025Pooled it
- Lesion Penetration and Activity Limit the Utility of Second-Line Injectable Agents in Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2021Pooled it
- Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019Guideline
- Alterations of human skin microbiome and expansion of antimicrobial resistance after systemic antibiotics.Science translational medicine · 2021Trial
- Discovery and development of a new oxazolidinone with reduced toxicity for the treatment of tuberculosis.Nature medicine · 2026Article
- Extrapolation of lung pharmacokinetics of bedaquiline across species using physiologically-based pharmacokinetic modelling.British journal of clinical pharmacology · 2025Article
- The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the Emergence of Resistance.The Journal of infectious diseases · 2025Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Article
- Drug distribution and efficacy of the DprE1 inhibitor BTZ-043 in the C3HeB/FeJ mouse tuberculosis model.Antimicrobial agents and chemotherapy · 2023Article
- Lung microenvironments harborAntimicrobial agents and chemotherapy · 2023Article
- Desorption Kinetics Evaluation for the Development of Validated Desorption Electrospray Ionization-Mass Spectrometric Assays for Drug Quantification in Tissue Sections.International journal of molecular sciences · 2023Article
- A Multimodal Desorption Electrospray Ionisation Workflow Enabling Visualisation of Lipids and Biologically Relevant Elements in a Single Tissue Section.Metabolites · 2023Article
- Spatial quantitation of antibiotics in bone tissue compartments by laser-capture microdissection coupled with UHPLC-tandem mass spectrometry.Analytical and bioanalytical chemistry · 2022Article
- Colocation of Lipids, Drugs, and Metal Biomarkers Using Spatially Resolved Lipidomics with Elemental Mapping.Analytical chemistry · 2022Article
- A Rabbit Model to Study Antibiotic Penetration at the Site of Infection for Nontuberculous Mycobacterial Lung Disease: Macrolide Case Study.Antimicrobial agents and chemotherapy · 2022Article
- Spatial relationships of intra-lesion heterogeneity in Mycobacterium tuberculosis microenvironment, replication status, and drug efficacy.PLoS pathogens · 2022Article
- On-Slide Heat Sterilization Enables Mass Spectrometry Imaging of Tissue Infected with High-Threat Pathogens Outside of Biocontainment: A Study Directed atJournal of the American Society for Mass Spectrometry · 2021Article
- Comparative Analysis of Pharmacodynamics in the C3HeB/FeJ Mouse Tuberculosis Model for DprE1 Inhibitors TBA-7371, PBTZ169, and OPC-167832.Antimicrobial agents and chemotherapy · 2021Article
- Laser Capture Proteomics: spatial tissue molecular profiling from the bench to personalized medicine.Expert review of proteomics · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tuberculosis is still a leading cause of morbidity and mortality worldwide. Improvements to existing drug regimens and the development of novel therapeutics are urgently required. The ability of dosed TB drugs to reach and sterilize bacteria within poorly-vascularized necrotic regions (caseum) of pulmonary granulomas is crucial for successful therapeutic intervention. Effective therapeutic regimens must therefore contain drugs with favorable caseum penetration properties. Current LC/MS methods for quantifying drug levels in biological tissues have limited spatial resolution capabilities, making it difficult to accurately determine absolute drug concentrations within small tissue compartments such as those found within necrotic granulomas. Here we present a protocol combining laser capture microdissection (LCM) of pathologically-distinct tissue regions with LC/MS quantification. This technique provides absolute quantification of drugs within granuloma caseum, surrounding cellular lesion and uninvolved lung tissue and, therefore, accurately determines whether bactericidal concentrations are being achieved. In addition to tuberculosis research, the technique has many potential applications for spatially-resolved quantification of drugs in diseased tissues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.