PulmoBind, an adrenomedullin-based molecular lung imaging tool.
Previous studies showed that adrenomedullin (AM) could be a promising agent for molecular imaging of the pulmonary circulation, with abundant specific binding sites at the pulmonary vascular endothelium. The purpose of this work was to design an AM-based compound that encompasses the desired imaging properties without posing safety issues for clinical applications.


METHODS
AM analogs were synthesized through solid-phase peptide synthesis. They were evaluated for (99m)Tc labeling efficiency and in vivo lung uptake. Biodistribution and hemodynamic characteristics of the lead compound were determined in anesthetized dogs as well as by a dosimetric analysis. Lung perfusion was evaluated in the monocrotaline model of pulmonary arterial hypertension in rats.


RESULTS
A cyclic AM (residues 22-52) analog encompassing a polyethylene glycol spacer and a tetrapeptide chelating moiety was found to possess the desired characteristics, with 90.7% ± 0.3% (mean ± SD) labeling efficiency, 40% lung uptake at 10 min after injection, and a favorable safety profile. Lung uptake of the (99m)Tc-labeled compound was markedly reduced in rats with pulmonary arterial hypertension.


CONCLUSIONS
This lead compound could be a suitable clinical imaging agent for the molecular diagnosis of disorders of the pulmonary circulation.
Laboratoire d'Études Moléculaires et Pharmacologiques des Peptides, INRS-Institut Armand-Frappier, Laval, Quebec, Canada.
Myriam
M
Létourneau
Quang Trinh
QT
Nguyen
François
F
Harel
Alain
A
Fournier
Jocelyn
J
Dupuis
D053607:Adrenomedullin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D062186:Arterial Pressure; D001692:Biological Transport; D004285:Dogs; D015195:Drug Design; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology*; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011652:Pulmonary Circulation; D051381:Rats; D013667:Technetium
D010446:Peptide Fragments; D010455:Peptides; C000603943:adrenomedullin (22-52), glycyl-glycyl-alanyl-glycyl-cysteinyl-(PEG)4-cysteinyl-; D053607:Adrenomedullin; D013667:Technetium
adrenomedullin; lung; molecular imaging; nuclear medicine; pulmonary hypertension