Evaluation of pulmonary perfusion using an endothelial cell tracer in supine humans and dogs

Objectives

To evaluate human pulmonary perfusion using a novel endothelial cell tracer.

Background

Pulmonary perfusion is not homogeneously distributed and its variations could be of diagnostic value.  PulmoBind is a ligand of the adrenomedullin receptor expressed in endothelial cells of lung capillaries.  The spatial distribution of human lung perfusion has never been evaluated using a molecular tracer.

Methods

Normal humans (n = 19) enrolled into the PulmoBind phase I trial were studied (Clinicaltrials.gov NCT01539889). They were injected with ^99mTc-PulmoBind for SPECT imaging.  Results were compared with ^99mTc-PulmoBind in quadruped mammals (dogs, n = 5).  Imaging was performed in the supine position and activity was determined as a function of cumulative voxels along different planes. 

Results

PulmoBind uptake in humans was 58%±1% (mean±SEM) of the injected dose.  Dorsal activity was 18.1%±2.1% greater than ventral, and caudal activity was 25.7%±1.6% greater than cranial.  Lateral activity was only mildly higher than medial by 7.0%±1.0%.  In supine dogs, similar but higher PulmoBind gradients were present: dorsal 28.6%±2.5%, caudal 34.1%±5.0% and lateral 18.1%±2.0%.

Conclusions

The perfused pulmonary circulation of supine humans, assessed by an adrenomedullin receptor ligand, is not homogeneously distributed with more prominent distribution in dorsal and caudal regions.  It is qualitatively similar to a supine quadruped mammal confirming the presence of a microcirculatory gravitational perfusion gradient detectable with this tracer. Future studies are needed to determine if this novel endothelial cell tracer could be used to detect physiologic and pathologic variations of lung perfusion.