The evaluation of lung function with PET.

In many ways, the lung is an ideal organ for study with positron emission tomography (PET). First, structure-function relations are homogeneous over larger areas than in other organs (reducing problems associated with otherwise relatively poor spatial resolution and partial-volume averaging). Second, many physiologic and metabolic processes can be studied, including pulmonary blood flow, ventilation, vascular permeability, endothelial receptor and enzyme function, among others. A variety of radiotracers have been used to evaluate pulmonary blood flow with PET, including 68Ga- or 11C-albumin microspheres administered intravenously, H2 15O administered by i.v. infusion, and 13N-N2 administered by inhalation. Pulmonary ventilation has been evaluated with both 13N-N2 and 19Ne gas, also administered by inhalation. In general, the relative advantage of one approach over another depends on site-specific cyclotron capacity and experience, and on the nature and timing of concomitant studies with other positron-emitting radiopharmaceuticals. The various blood flow methods have been used primarily in studies of pulmonary gas exchange, in both experimental animals and in humans. Acute lung injury is usually defined by both an increase in extravascular water (pulmonary edema) and an increase in the permeability of the pulmonary endothelium to protein. Both processes can easily be evaluated with PET. Extravascular water is measured by a combination of scans with i.v. H2 15O and C15O. The latter is administered by inhalation to label the blood pool (to calculate intravascular water concentrations). Pulmonary vascular permeability has been evaluated with dynamic sequential imaging after either 68Ga-transferrin or 11C-methylalbumin infusions. The rate of uptake of either tracer into the pulmonary extravascular space is an index of "leakiness" of the pulmonary endothelium, and is quantified as the pulmonary transcapillary escape rate, or PTCER. PTCER appears to be a highly sensitive index of acute lung injury. Two receptor/ enzyme systems that have been evaluated include the beta-adrenergic receptor system (using 11CGP-12177 as the ligand) and angiotensin converting enzyme (using 18F-fluorocaptopril). In each case, the object is to measure Bmax, or the maximum binding-capacity for the ligand in question. Changes in Bmax can be used to infer changes in protein expression of the receptor or enzyme, or can be used to quantify adequacy of therapy with inhibitor drugs. Given the highly active nature of the pulmonary endothelium, it is likely that many other pulmonary receptor or enzyme systems can be studied in a similar fashion.