Radioiodinated metaiodobenzylguanidine (MIBG) has been shown to be extracted in the lung by an active, sodium-dependent, saturable transport system similar to that which extracts norepinephrine. Accordingly, first transit uptake of MIBG has been investigated as a method for in vivo evaluation of pulmonary biogenic amine metabolism. Issues that still must be resolved include the degree to which MIBG extraction is affected by simple loss of available vascular surface (in distinction to changes in amine metabolism). If MIBG lung extraction is altered by loss of pulmonary vascular surface alone, then a tracer must be found that can serve as a simultaneous monitor of vascular surface loss in order to allow normalization of the MIBG data. One tracer with such potential is radioiodinated iodoamphetamine (IMP). Accordingly, an experimental model of pulmonary vascular surface loss (lobar ligatures) was applied in an isolated-perfused lung model with simultaneous administration of MIBG and IMP. A linear relationship was found between MIBG extraction and percent lung surface loss by weight (n = 21, r = 0.75, P less than 0.05). Addition of IMP (1 or 10 microM) to media containing MIBG (1 microM) (n = 28) inhibited overall MIBG extraction, but decreases in MIBG uptake with vascular surface loss were otherwise parallel to those in experiments without IMP. IMP, however, did not adequately reflect vascular surface loss at the concentrations used in this study (extraction of IMP 1 microM = 31.2% +/- 12.9% in control vs 32.7% +/- 7.7% with greater than 50% lung surface loss, n = 18, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)