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About Lesson
Abstract Body:

Background: After completing treatment for tuberculosis (TB), millions of TB survivors each year suffer from chronic lung damage. Unfortunately, the nature of this lung damage is not well understood, which limits the ability to care for patients suffering from chronic lung disease after TB. Post-TB lung disease (PTLD) is a multifactorial process that leads to tissue remodeling of the extracellular matrix components, which include fibrillar collagen. 68Ga-CBP8, is a peptide-based type I collagen–targeted probe developed for imaging of tissue fibrosis to evaluate collagen remodeling [1-3]. We hypothesized that molecular imaging of pulmonary fibrosis in TB patients would provide valuable data on pathogenesis and serve as an early-disease biomarker for PTLD. Newly identified adult patients with their first episode of Xpert MTB/RIF-positive, rifampin resistance-negative pulmonary TB were enrolled within 8 weeks after TB treatment initiation for the first evaluation of a collagen-specific PET imaging probe in TB patients.

Methods: We prospectively enrolled patients with recently confirmed active pulmonary TB with a moderate to severe lung burden as determined by chest X-ray. Patients were intravenously injected 68Ga-CBP8 followed by a PET/CT [2]. The images were analyzed using MIM and volumes of interest (VOIs) were drawn using the CT as reference. The percentage of affected lung area was determined by histogram analysis of segmented PET VOIs. Pulmonary function tests and evaluation of blood and sputum inflammatory markers were also performed.

Results: Nineteen patients (age 19-58, 4 females) were imaged. The mean administered activity of 68Ga-CBP8 was 120.5 ± 33.2 MBq. There were no adverse or clinically detectable pharmacologic effects in any of the subjects. No adverse effects related to probe administration were detected. 68Ga-CBP8 demonstrated an extracellular distribution with predominantly rapid renal clearance. CT demonstrated heterogeneity of pulmonary TB, including multiple different lesions (e.g., nodular opacities and cavitary disease) simultaneously within individual patients. Whole lung and lesion VOIs [122 pulmonary lesions (28 cavitary) and 19 control regions] were analyzed. The mean percentage affected lung (based on PET values with SUVmean) was 4.9 ± 3.4 % (range, 0.3 – 13.8 %). 68Ga-CBP8 localized in the areas of tissue remodeling (based on tissue density and CT characteristics) with an SUVmean of 0.7 ± 0.4 for lesions (patchy consolidations and nodular opacities) and 0.6 ± 0.3 for cavities. Increased tracer signal was also observed in regions where fibrosis was not apparent by CT, suggesting that 68Ga-CBP8 PET may detect active collagen deposition that is not yet visible by anatomical imaging.

Conclusions: We present data from a pilot study evaluating collagen-specific PET to evaluate fibrotic changes in TB patients. 68Ga-CBP8 PET signal localized to areas of cavitation and consolidation observed in CT. PET imaging of fibrosis represents a clinically translatable tool to noninvasively evaluate early fibrotic changes that could lead to optimization of the diagnosis and management of PTLD.

Author

Alvaro A. Ordonez
Perelman School of Medicine at the University of Pennsylvania
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