More Study Needed for Mechanisms Underlying the 67Ga-Pulmonary Leak Index

Abstract

We read with interest the report in the December 1993 issue of Chest by Raijmakers et al1Raijmakers PGHM Groeneveld ABJ Schneider AJ Teule GJJ Van Lingen A Eijsman L Et Al Transvascular transport of 67Ga in the lungs after cardiopulmonary bypass surgery..Chest. 1993; 104: 1825-1832Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar using transferrin, labeled with 67Ga, as a marker of pulmonary vascular permeability after cardiopulmonary bypass surgery. Pulmonary permeability in this setting has been attributed to neutrophil sequestration in pulmonary capillaries after activation of complement, and subsequent endothelial damage from neutrophil-derived proteolytic enzymes and oxygen radicals. The use of transferrin-bound gallium to indicate pulmonary permeability, in this setting, poses methodologic problems, which are not fully addressed by the authors. First, 67Ga will dissociate from transferrin in the presence of binding proteins with a higher affinity for gallium, such as lactoferrin. The secondary granules of neutrophils are rich in lactoferrin, and disruption of neutrophils in inflammation is known to cause leakage of this protein. Lactoferrin is also exocytosed by activated neutrophils. The complicated kinetics of 67Ga-transferrin association and dissociation, therefore, confounds the use of this radionuclide-protein complex to characterize a permeability model that is largely based on the presence of sequestered and activated neutrophils in the pulmonary microvasculature. It is possible that 67Ga, independent of transferrin, is taken up by neutrophils in the pulmonary capillaries, as well as by extracelhilar lactoferrin, and accounts for the radioactivity detected by scintillation scanning of the lungs. We investigated the pulmonary disposition of 67Ga in patients with pneumocystis pneumonia, which is also associated with increased pulmonary vascular permeability and 67Ga uptake.2Smith RL Berkowitz KA Lewis ML Pulmonary disposition of gallium-67 in patients with pneumocystis pneumonia: an analysis using bronchoalveolar lavage..J Nucl Med. 1992; 33: 512-515PubMed Google Scholar We found no significant difference between mean bronchoalveolar lavage transferrin concentrations in patients with pneumocystis pneumonia, associated with pulmonary uptake of 67Ga, and patients without infection and negative gallium scanning. Furthermore, radioactivity in the bronchoalveolar lavage supernatant correlated with the presence of neutrophil alveolitis, but not with transferrin concentrations. The extracellular release of lactoferrin, which binds gallium with greater affinity than transferrin, may have accounted for the 67Ga radioactivity in the lavage supernatant from patients with pneumocystis pneumonia and neutrophil alveolitis. Thus, determination of pulmonary 67Ga uptake may not provide an accurate assessment of the permeability of the microvasculature to transferrin, but rather, it may reflect the instability of the 67Ga-transferrin complex in the presence of neutrophil activation and inflammation. More Study Needed for Mechanisms Underlying the 67Ga-Pulmonary Leak IndexCHESTVol. 106Issue 5PreviewWe thank Drs. Smith and Berkowitz for their valuable comments on our paper (Chest1993; 104:1825-32) describing an increased 1-h pulmonary uptake of IV injected 67Ga, corrected for blood content in patients after prolonged cardiac surgery with cardiopulmonary bypass (CPB). They question our interpretation that the pulmonary 67Ga uptake, ie, the pulmonary leak index (PLI), is a measure of microvascular permeability in the lungs. They suggest that the increased 67Ga-PLI is not caused by increased microvascular transferrin transport but by increased binding to neutrophils, lactoferrin, or both within the pulmonary microvasculature. Full-Text PDF