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

Abstract

BackgroundPulmonary perfusion is not spatially homogeneously distributed, and its variations could be of diagnostic value in lung vascular disease. PulmoBind is a ligand of the adrenomedullin receptor densely expressed in endothelial cells of lung capillaries. The aim of this study was to evaluate spatial distribution of human lung perfusion by using this novel molecular tracer of the pulmonary vascular endothelium.MethodsNormal 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 distribution of activity was determined as a function of cumulative voxels along the different anatomical planes.ResultsPulmoBind 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 %.ConclusionsThe 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 such as in pulmonary hypertension.Clinical trialClinicalTrial.gov, NCT01539889

SPECT imaging of pulmonary vascular disease in bleomycin-induced lung fibrosis using a vascular endothelium tracer

“…The limited anatomical resolution of SPECT imaging in rodents with small lungs hampers precise evaluation of the distribution of 99m Tc-PulmoBind and the detection of heterogeneity of distribution. In a larger animals (dog) and in humans, we showed that 99m Tc-PulmoBind lung distribution follows gravitational and non-gravitational gradients in normal conditions that are modified by pathology [ 18 ]. Furthermore, in humans with group I PH, we derived a “heterogeneity perfusion index” and showed its utility in quantifying abnormal distribution of 99m Tc-PulmoBind in these subjects [ 10 ].…”