01 March 2017 by Jocelyn Dupuis

Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

Background

The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium.  PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study.

Methods

Thirty patients with pulmonary arterial hypertension (PAH, n=23) or chronic thromboembolic PH (CTEPH, n=7) in WHO functional class II (n=26) or III (n=4) were compared to 15 healthy controls.  Lung SPECT was performed after injection of 15 mCi 99mTc‑PulmoBind in supine position.  Qualitative and semi-quantitative analyses of lung uptake were performed.  Reproducibility of repeated testing was evaluated in controls after 1 month.

Results

PulmoBind injection was well tolerated without any serious adverse event.  Imaging was markedly abnormal in PH with ~50% of subjects showing moderate to severe heterogeneity of moderate to severe extent.  The abnormalities were unevenly distributed between the right and left lungs as well as within each lung.  Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH.  There were no segmental defects in controls.  The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65%±28%) vs controls (41%±13%, p=0.0003).  In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal.  Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution.

Conclusions

In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using 99mTc‑PulmoBind was safe and reproducible.  PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel agent are justified.

Key Contributors

François Harel, MD PhD,1 3 David Langleben, MD,4 Steve Provencher, MD,5 Alain Fournier, PhD,6 Vincent Finnerty, MSc,1 Quang T Nguyen, PhD,1 Myriam Letourneau, MSc, 6 Xavier Levac, MSc,1 Gad Abikhzer , MD,4 Jean Guimond, MD,5 Asmaa Mansour, MSc, 7 Marie Claude Guertin, PhD,7 and Jocelyn Dupuis, MD PhD,1, 2 From the 1Research Center of the Montreal Heart Institute; 2Départment de Médicine et de 3Radiologie de l’Université de Montréal, Montreal, Canada; 4Lady Davis Institute and Jewish General Hospital, McGill University, Montreal, Canada; 5Institut Universitaire de Cardiologie et Pneumologie de Québec, Quebec, Canada; 6INRS-Institut Armand-Frappier, Laval, Quebec; 7Montreal Health Innovation Coordination Center.


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