title: Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial.
abstract: OBJECTIVE
  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 mCi99mTc-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 using99mTc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and direct comparisons to lung perfusion agents such as labeled macro-aggregates of albumin are needed.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT02216279.
authors.affiliation: Research Center, Montreal Heart Institute, 5000, Belanger Street, Montreal, QC, H1T 1C8, Canada.|Department of Nuclear Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Harel
authors.affiliation: Lady Davis Institute and Jewish General Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Langleben
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada.
authors.forename: Steve
authors.initials: S
authors.lastname: Provencher
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.affiliation: Research Center, Montreal Heart Institute, 5000, Belanger Street, Montreal, QC, H1T 1C8, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Finnerty
authors.affiliation: Research Center, Montreal Heart Institute, 5000, Belanger Street, Montreal, QC, H1T 1C8, Canada.
authors.forename: Quang T
authors.initials: QT
authors.lastname: Nguyen
authors.affiliation: INRS-Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Letourneau
authors.affiliation: Research Center, Montreal Heart Institute, 5000, Belanger Street, Montreal, QC, H1T 1C8, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: Levac
authors.affiliation: Lady Davis Institute and Jewish General Hospital, McGill University, Montréal, Québec, Canada.
authors.forename: Gad
authors.initials: G
authors.lastname: Abikhzer
authors.affiliation: Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Guimond
authors.affiliation: Montreal Health Innovation Coordination Center, Montréal, QC, Canada.
authors.forename: Asmaa
authors.initials: A
authors.lastname: Mansour
authors.affiliation: Montreal Health Innovation Coordination Center, Montréal, QC, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guertin
authors.affiliation: Research Center, Montreal Heart Institute, 5000, Belanger Street, Montreal, QC, H1T 1C8, Canada. dupuisj@me.com.|Department of Medicine, Université de Montréal, Montréal, Québec, Canada. dupuisj@me.com.
authors.forename: Jocelyn
authors.identifier: http://orcid.org/0000-0002-3193-1014
authors.initials: J
authors.lastname: Dupuis
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000009:adverse effects*; D015203:Reproducibility of Results; D012449:Safety
keywords: Adrenomedullin; Molecular imaging; Nuclear medicine; Peptide; Pulmonary embolism; Pulmonary hypertension