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Early Changes by (18)Fluorodeoxyglucose positron emission tomography coregistered with computed tomography predict outcome after Mycobacterium tuberculosis infection in cynomolgus macaques.

ABSTRACT: Cynomolgus macaques infected with low-dose Mycobacterium tuberculosis develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection. (18)Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished active-disease and latent outcomes. Macaques (n = 10) were infected with low-dose M. tuberculosis with FDG PET/CT performed during infection. At 24 weeks postinfection, animals were classified as having active disease (n = 3) or latent infection (n = 6), with one "percolator" monkey. Imaging characteristics (e.g., lesion number, metabolic activity, size, mineralization, and distribution of lesions) were compared among active and latent groups. As early as 3 weeks postinfection, more pulmonary granulomas were observed in animals that would later develop active disease than in those that would develop latent infection. Over time, new lesions developed in active-disease animals but not in latent animals. Granulomas and mediastinal lymph nodes from active-disease but not latent animals consistently increased in metabolic activity at early time points. The presence of fewer lesions at 3 weeks and the lack of new lesion development in animals with latent infection suggest that innate and rapid adaptive responses are critical to preventing active tuberculosis. A greater emphasis on innate responses and/or rapid recruitment of adaptive responses, especially in the airway, should be emphasized in newer vaccine strategies.

SUBMITTER: Coleman MT

PROVIDER: S-EPMC4019174 | biostudies-other | 2014 Jun

REPOSITORIES: biostudies-other

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Early Changes by (18)Fluorodeoxyglucose positron emission tomography coregistered with computed tomography predict outcome after Mycobacterium tuberculosis infection in cynomolgus macaques.

Coleman M Teresa MT Maiello Pauline P Tomko Jaime J Frye Lonnie James LJ Fillmore Daniel D Janssen Christopher C Klein Edwin E Lin Philana Ling PL

Infection and immunity 20140324 6

Cynomolgus macaques infected with low-dose Mycobacterium tuberculosis develop both active tuberculosis and latent infection similar to those of humans, providing an opportunity to study the clinically silent early events in infection. (18)Fluorodeoxyglucose radiotracer with positron emission tomography coregistered with computed tomography (FDG PET/CT) provides a noninvasive method to measure disease progression. We sought to determine temporal patterns of granuloma evolution that distinguished ...[more]

PMID: 24664509

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Project description:PURPOSE:We sought to investigate the ability of mid-treatment (18)F-fluorodeoxyglucose positron emission tomography (PET) studies to objectively and spatially quantify esophageal injury in vivo from radiation therapy for non-small cell lung cancer. METHODS AND MATERIALS:This retrospective study was approved by the local institutional review board, with written informed consent obtained before enrollment. We normalized (18)F-fluorodeoxyglucose PET uptake to each patient's low-irradiated region (<5 Gy) of the esophagus, as a radiation response measure. Spatially localized metrics of normalized uptake (normalized standard uptake value [nSUV]) were derived for 79 patients undergoing concurrent chemoradiation therapy for non-small cell lung cancer. We used nSUV metrics to classify esophagitis grade at the time of the PET study, as well as maximum severity by treatment completion, according to National Cancer Institute Common Terminology Criteria for Adverse Events, using multivariate least absolute shrinkage and selection operator (LASSO) logistic regression and repeated 3-fold cross validation (training, validation, and test folds). This 3-fold cross-validation LASSO model procedure was used to predict toxicity progression from 43 asymptomatic patients during the PET study. Dose-volume metrics were also tested in both the multivariate classification and the symptom progression prediction analyses. Classification performance was quantified with the area under the curve (AUC) from receiver operating characteristic analysis on the test set from the 3-fold analyses. RESULTS:Statistical analysis showed increasing nSUV is related to esophagitis severity. Axial-averaged maximum nSUV for 1 esophageal slice and esophageal length with at least 40% of axial-averaged nSUV both had AUCs of 0.85 for classifying grade 2 or higher esophagitis at the time of the PET study and AUCs of 0.91 and 0.92, respectively, for maximum grade 2 or higher by treatment completion. Symptom progression was predicted with an AUC of 0.75. Dose metrics performed poorly at classifying esophagitis (AUC of 0.52, grade 2 or higher mid treatment) or predicting symptom progression (AUC of 0.67). CONCLUSIONS:Normalized uptake can objectively, locally, and noninvasively quantify esophagitis during radiation therapy and predict eventual symptoms from asymptomatic patients. Normalized uptake may provide patient-specific dose-response information not discernible from dose.

Dataset Information

Early Changes by (18)Fluorodeoxyglucose positron emission tomography coregistered with computed tomography predict outcome after Mycobacterium tuberculosis infection in cynomolgus macaques.

Publications

Early Changes by (18)Fluorodeoxyglucose positron emission tomography coregistered with computed tomography predict outcome after Mycobacterium tuberculosis infection in cynomolgus macaques.

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