title: Single-Photon Emission Computed Tomography/Computed Tomography Imaging in a Rabbit Model of Emphysema Reveals Ongoing Apoptosis In Vivo.
abstract: Evaluation of lung disease is limited by the inability to visualize ongoing pathological processes. Molecular imaging that targets cellular processes related to disease pathogenesis has the potential to assess disease activity over time to allow intervention before lung destruction. Because apoptosis is a critical component of lung damage in emphysema, a functional imaging approach was taken to determine if targeting apoptosis in a smoke exposure model would allow the quantification of early lung damage in vivo. Rabbits were exposed to cigarette smoke for 4 or 16 weeks and underwent single-photon emission computed tomography/computed tomography scanning using technetium-99m-rhAnnexin V-128. Imaging results were correlated with ex vivo tissue analysis to validate the presence of lung destruction and apoptosis. Lung computed tomography scans of long-term smoke-exposed rabbits exhibit anatomical similarities to human emphysema, with increased lung volumes compared with controls. Morphometry on lung tissue confirmed increased mean linear intercept and destructive index at 16 weeks of smoke exposure and compliance measurements documented physiological changes of emphysema. Tissue and lavage analysis displayed the hallmarks of smoke exposure, including increased tissue cellularity and protease activity. Technetium-99m-rhAnnexin V-128 single-photon emission computed tomography signal was increased after smoke exposure at 4 and 16 weeks, with confirmation of increased apoptosis through terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased tissue neutral sphingomyelinase activity in the tissue. These studies not only describe a novel emphysema model for use with future therapeutic applications, but, most importantly, also characterize a promising imaging modality that identifies ongoing destructive cellular processes within the lung.
authors.affiliation: 1 Department of Anesthesiology.|2 Department of Medicine.
authors.forename: Monica P
authors.initials: MP
authors.lastname: Goldklang
authors.affiliation: 2 Department of Medicine.
authors.forename: Yared
authors.initials: Y
authors.lastname: Tekabe
authors.affiliation: 1 Department of Anesthesiology.
authors.forename: Tina
authors.initials: T
authors.lastname: Zelonina
authors.affiliation: 1 Department of Anesthesiology.
authors.forename: Jordis
authors.initials: J
authors.lastname: Trischler
authors.affiliation: 1 Department of Anesthesiology.
authors.forename: Rui
authors.initials: R
authors.lastname: Xiao
authors.affiliation: 1 Department of Anesthesiology.
authors.forename: Kyle
authors.initials: K
authors.lastname: Stearns
authors.affiliation: 3 Institute of Comparative Medicine, and.
authors.forename: Alexander
authors.initials: A
authors.lastname: Romanov
authors.affiliation: 4 Preclinical Pharmacology R&D, Advanced Accelerator Applications (Italy), Saint-Genis-Pouilly, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Muzio
authors.affiliation: 1 Department of Anesthesiology.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiomi
authors.affiliation: 2 Department of Medicine.
authors.forename: Lynne L
authors.initials: LL
authors.lastname: Johnson
authors.affiliation: 1 Department of Anesthesiology.|2 Department of Medicine.|5 Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, New York; and.
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: D'Armiento
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D003187:Compliance; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D011014:Pneumonia / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000150:complications / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000503:physiopathology; D011817:Rabbits; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D012906:Smoke; D013667:Technetium / Q000378:metabolism; D013997:Time Factors
chemical_list: D017304:Annexin A5; D012906:Smoke; D013667:Technetium
keywords: apoptosis; emphysema; molecular imaging; smoke