Evaluating pulmonary vascular permeability with radiolabeled proteins: an error analysis

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Abstract
Using techniques of mathematical simulation, we compared two methods of evaluating pulmonary vascular permeability, i.e., transvascular protein flux. Both methods calculate a transport rate constant [pulmonary transcapillary escape rate (PTCER)] after making external radiation detection measurements of an intravenously administered radiolabeled protein. With one method, lung tissue time-activity data are acquired by positron emission tomography (PET) and are interpreted with a two-compartment model. With the other method, the time-activity data are acquired with simple detector probes and are interpreted by linear regression after normalizing for various physical factors (slope-intercept or SI method). The results show that significant errors in calculating PTCER can result from using the SI method, because it ignores the effects of back-flux on the tissue time-activity measurements. Both methods produce errors if the data analysis includes activity from vascular volumes not involved in tracer exchange with the extravascular compartment. Significant errors can also occur with the PET method, particularly when permeability is nearly normal, if pulmonary vascular volume changes significantly during the period of data collection. On balance, the PET method appears to be the method of choice for accurately evaluating pulmonary vascular permeability by protein flux measurements, although both methods may be useful in clinical applications.