Research Center, Montreal Heart Institute, 5000, Belanger, Montreal, QC, H1T 1C8, Canada.
Department of Medicine, Université de Montréal, Montréal, Québec, Canada.
EJNMMI Res. 2016 Dec;6(1):43. doi: 10.1186/s13550-016-0198-3. Epub 2016 May 27.
Pulmonary 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.
Normal humans (n = 19) enrolled into the PulmoBind phase I trial were studied (Clinicaltrials.gov. NCT01539889 ). They were injected with (99m)Tc-PulmoBind for SPECT imaging. Results were compared with (99m)Tc-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.
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 %.
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 such as in pulmonary hypertension.
ClinicalTrial.gov, NCT01539889.
肺灌注在空间上分布不均匀，其变化可能对肺血管疾病具有诊断价值。PulmoBind 是一种在肺毛细血管内皮细胞中高度表达的肾上腺髓质素受体配体。本研究旨在使用这种新型肺血管内皮细胞分子示踪剂评估人类肺灌注的空间分布。
本研究纳入了参加 PulmoBind Ⅰ期临床试验的 19 名正常志愿者（ClinicalTrials.gov，NCT01539889）。志愿者接受放射性核素标记的 PulmoBind（99mTc-PulmoBind）SPECT 成像。结果与四足哺乳动物（狗，n=5）中的 99mTc-PulmoBind 进行比较。成像在仰卧位进行，通过沿不同解剖平面累积的体素来确定活性的分布。
在人体中，PulmoBind 的摄取量为注射剂量的 58±1%（平均值±SEM）。背部的活性比腹部高 18.1±2.1%，尾部的活性比头部高 25.7±1.6%。侧部的活性仅比内侧高 7.0±1.0%。在仰卧位的狗中，也存在类似但更高的 PulmoBind 梯度：背部 28.6±2.5%，尾部 34.1±5.0%，侧部 18.1±2.0%。
用肾上腺髓质素受体配体评估仰卧位人体的肺循环灌注不均匀，背部和尾部分布更为明显。它与仰卧位四足哺乳动物的结果类似，证实了这种示踪剂可以检测到微循环重力灌注梯度。未来的研究需要确定这种新型内皮细胞示踪剂是否可用于检测肺灌注的生理和病理变化，如肺动脉高压。
ClinicalTrials.gov，NCT01539889。
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