TY - JOUR T1 - PulmoBind, an Adrenomedullin-Based Molecular Lung Imaging Tool JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1789 LP - 1796 DO - 10.2967/jnumed.112.118984 VL - 54 IS - 10 AU - Myriam Létourneau AU - Quang Trinh Nguyen AU - François Harel AU - Alain Fournier AU - Jocelyn Dupuis Y1 - 2013/10/01 UR - http://jnm.snmjournals.org/content/54/10/1789.abstract N2 - 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 99mTc 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 99mTc-labeled compound was markedly reduced in rats with pulmonary arterial hypertension. Conclusion: This lead compound could be a suitable clinical imaging agent for the molecular diagnosis of disorders of the pulmonary circulation. ER -