Caspase-Based PET for Evaluating Pro-Apoptotic Treatments in a Tuberculosis Mouse Model

Purpose Despite recent advances in antimicrobial treatments, tuberculosis (TB) remains a major global health threat. Mycobacterium tuberculosis proliferates in macrophages, preventing apoptosis by inducing anti-apoptotic proteins leading to necrosis of the infected cells. Necrosis then leads to incr...

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Bibliographic Details
Published in:Molecular imaging and biology 2020-12, Vol.22 (6), p.1489-1494
Main Authors: Ordonez, Alvaro A., Abhishek, Sudhanshu, Singh, Alok K., Klunk, Mariah H., Azad, Babak Benham, Aboagye, Eric O., Carroll, Laurence, Jain, Sanjay K.
Format: Article
Language:English
Subjects:
Animal models
Antiinfectives and antibacterials
Antimicrobial agents
Apoptosis
Brief Article
Caspase-3
Cisplatin
Emission analysis
Evaluation
Fluorine isotopes
Global health
Health risks
Imaging
Immune system
Immunosuppressive agents
Macrophages
Medicine
Medicine & Public Health
Necrosis
Positron emission
Positron emission tomography
Public health
Radioactive tracers
Radiology
Tomography
Tuberculosis
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Summary:Purpose Despite recent advances in antimicrobial treatments, tuberculosis (TB) remains a major global health threat. Mycobacterium tuberculosis proliferates in macrophages, preventing apoptosis by inducing anti-apoptotic proteins leading to necrosis of the infected cells. Necrosis then leads to increased tissue destruction, reducing the penetration of antimicrobials and immune cells to the areas where they are needed most. Pro-apoptotic drugs could be used as host-directed therapies in TB to improve antimicrobial treatments and patient outcomes. Procedure We evaluated [ 18 F]-ICMT-11, a caspase-3/7-specific positron emission tomography (PET) radiotracer, in macrophage cell cultures and in an animal model of pulmonary TB that closely resembles human disease. Results Cells infected with M. tuberculosis and treated with cisplatin accumulated [ 18 F]-ICMT-11 at significantly higher levels compared with that of controls, which correlated with levels of caspase-3/7 activity. Infected mice treated with cisplatin with increased caspase-3/7 activity also had a higher [ 18 F]-ICMT-11 PET signal compared with that of untreated infected animals. Conclusions [ 18 F]-ICMT-11 PET could be used as a noninvasive approach to measure intralesional pro-apoptotic responses in situ in pulmonary TB models and support the development of pro-apoptotic host-directed therapies for TB.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-020-01494-9