PulmoBind, an Adrenomedullin-Based Molecular Lung Imaging Tool
| Autor: | François Harel, Jocelyn Dupuis, Alain Fournier, Myriam Létourneau, Quang Trinh Nguyen |
|---|---|
| Přispěvatelé: | Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Research Centre, Montreal Heart Institute - Institut de Cardiologie de Montréal, Department of Radiology, Université de Montréal (UdeM), Department of Medicine |
| Rok vydání: | 2013 |
| Předmět: |
Male
Pulmonary Circulation Biodistribution Pathology medicine.medical_specialty [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging Hypertension Pulmonary [SDV]Life Sciences [q-bio] Molecular Sequence Data Hemodynamics [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine lung Dogs In vivo pulmonary hypertension medicine Animals Humans Arterial Pressure Familial Primary Pulmonary Hypertension Radiology Nuclear Medicine and imaging Amino Acid Sequence nuclear medicine Lung Tetrapeptide business.industry Technetium Biological Transport molecular imaging medicine.disease Pulmonary hypertension Peptide Fragments Rats Adrenomedullin medicine.anatomical_structure Drug Design adrenomedullin Female Molecular imaging Peptides business |
| Zdroj: | Journal of Nuclear Medicine Journal of Nuclear Medicine, Society of Nuclear Medicine, 2013, 54 (10), pp.1789-96. ⟨10.2967/jnumed.112.118984⟩ |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.112.118984 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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