4.4 Article

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

期刊

MOLECULAR IMAGING AND BIOLOGY
卷 22, 期 6, 页码 1489-1494

出版社

SPRINGER
DOI: 10.1007/s11307-020-01494-9

关键词

Tuberculosis; PET; Apoptosis; Caspase; Imaging

资金

  1. National Institutes of Health Director's Transformative Research Award [R01-EB020539]
  2. MRC [MR/J007986/1, MR/N020782/1] Funding Source: UKRI

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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 [F-18]-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 [F-18]-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 [F-18]-ICMT-11 PET signal compared with that of untreated infected animals. Conclusions [F-18]-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.

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