1. ¹Pulmonary and Critical Care, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98105, USA
2. ²Tulane Regional Primate Research Center, Covington, Louisiana 70435, USA
3. ³Center for Gene Therapy, Louisiana State University, New Orleans, Louisiana 70112, USA

Correspondence: Daniel J. Weiss, Fax: (802) 656-8926. E-mail: daniel.weiss@vtmednet.org.

Received 11 July 2001; Accepted 19 October 2001.

Abstract

Use of perflubron (LiquiVent^R) and other perfluorochemical liquids during intratracheal administration of adenovirus and AAV vectors has been shown to improve total gene expression as well as distribution of expression throughout lungs of spontaneously breathing rodents. To determine if this method could be safely and easily extended to non-human primates, we carried out a pilot investigation in six spontaneously breathing rhesus macaques. Two animals received bronchoscopic administration of recombinant adenovirus vector (type 5 E1-deleted AdCMVlacZ, 4.610¹⁰ plaque forming units/animal), two animals received vector followed by instillation of perflubron, and two animals received perflubron alone. Instillation of perflubron was well tolerated by the animals and, once recovered from anesthesia, all animals behaved and fed normally until lung harvest. Serial X-rays demonstrated that the perflubron had cleared from lungs of three animals by 48 hours after administration; the fourth animal had a small amount of residual perflubron. Apart from a mild elevation in hepatocellular enzymes, no significant abnormality was noted in complete blood count or serum electrolytes and chemistries. In animals receiving either vector alone or vector with perflubron, in situ -galactosidase expression was observed in a variety of cells including large airway, bronchiolar, and alveolar epithelial cells. In summary, use of perflubron was well tolerated in spontaneously breathing macaques. Further studies in larger numbers of animals will help assess the potential efficacy of perflubron for enhancing gene expression and elucidate effects on local and systemic inflammatory responses.