99MTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment

Authors

Said H. Audi, Marquette UniversityFollow
Anne V. Clough, Marquette UniversityFollow
Steven T. Haworth, Medical College of WisconsinFollow
Meetha Medhora, Medical College of Wisconsin
Mahsa Ranji, University of Wisconsin - Milwaukee
John C. Densmore, Medical College of Wisconsin
Elizabeth R. Jacobs, Medical College of WisconsinFollow

Document Type

Article

Language

eng

Format of Original

11 p.

Publication Date

10-2016

Publisher

Lippincott Williams & Wilkins, Inc.

Source Publication

Shock

Source ISSN

1073-2322

Abstract

^99mTc-Hexamethylpropyleneamine oxime (HMPAO) is a clinical single-photon emission computed tomography biomarker of tissue oxidoreductive state. Our objective was to investigate whether HMPAO lung uptake can serve as a preclinical marker of lung injury in two well-established rat models of human acute lung injury (ALI).

Rats were exposed to >95% O₂ (hyperoxia) or treated with intratracheal lipopolysaccharide (LPS), with first endpoints obtained 24 h later. HMPAO was administered intravenously before and after treatment with the glutathione-depleting agent diethyl maleate (DEM), scintigraphy images were acquired, and HMPAO lung uptake was quantified from the images. We also measured breathing rates, heart rates, oxygen saturation, bronchoalveolar lavage (BAL) cell counts and protein, lung homogenate glutathione (GSH) content, and pulmonary vascular endothelial filtration coefficient (K_f).

For hyperoxia rats, HMPAO lung uptake increased after 24 h (134%) and 48 h (172%) of exposure. For LPS-treated rats, HMPAO lung uptake increased (188%) 24 h after injury and fell with resolution of injury. DEM reduced HMPAO uptake in hyperoxia and LPS rats by a greater fraction than in normoxia rats. Both hyperoxia exposure (18%) and LPS treatment (26%) increased lung homogenate GSH content, which correlated strongly with HMPAO uptake. Neither of the treatments had an effect on K_f at 24 h. LPS-treated rats appeared healthy but exhibited mild tachypnea, BAL, and histological evidence of inflammation, and increased wet and dry lung weights. These results suggest the potential utility of HMPAO as a tool for detecting ALI at a phase likely to exhibit minimal clinical evidence of injury.

Comments

Accepted version. Shock, Vol. 46, No. 4 (October 2016): 420-430. DOI. © 2016 Lippincott Williams & Wilkins, Inc. Used with permission.

Said H. Audi was affiliated with Medical College of Wisconsin at the time of publication.

Recommended Citation

Audi, Said H.; Clough, Anne V.; Haworth, Steven T.; Medhora, Meetha; Ranji, Mahsa; Densmore, John C.; and Jacobs, Elizabeth R., "99MTc-Hexamethylpropyleneamine Oxime Imaging for Early Detection of Acute Lung Injury in Rats Exposed to Hyperoxia or Lipopolysaccharide Treatment" (2016). Biomedical Engineering Faculty Research and Publications. 427.
https://epublications.marquette.edu/bioengin_fac/427