Molecular Imaging of Monocrotaline-Induced Pulmonary Vascular Disease with Radiolabeled Linear Adrenomedullin
| Autor: | Annick Préfontaine, Quang Trinh Nguyen, Alain Fournier, Myriam Létourneau, François Harel, Jocelyn Dupuis, Yan Fu |
|---|---|
| Přispěvatelé: | Research Center, Montreal Heart Institute, Université de Montréal (UdeM), Department of Medicine, Department of Radiology, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP) |
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty MESH: Isotope Labeling MESH: Rats Metabolic Clearance Rate Hypertension Pulmonary MESH: Rats Sprague-Dawley MESH: Monocrotaline Rats Sprague-Dawley Adrenomedullin Right ventricular hypertrophy In vivo Internal medicine medicine Animals MESH: Animals MESH: Lung Tissue Distribution Radiology Nuclear Medicine and imaging MESH: Tissue Distribution Radionuclide Imaging Receptor Lung MESH: Organ Specificity MESH: Metabolic Clearance Rate Monocrotaline Receptor activity-modifying protein MESH: Hypertension Pulmonary Chemistry Technetium medicine.disease Pulmonary hypertension MESH: Adrenomedullin MESH: Male Rats Endocrinology medicine.anatomical_structure Organ Specificity [SDV.TOX]Life Sciences [q-bio]/Toxicology Isotope Labeling MESH: Technetium Radiopharmaceuticals MESH: Radiopharmaceuticals Ex vivo |
| Zdroj: | Journal of Nuclear Medicine Journal of Nuclear Medicine, Society of Nuclear Medicine, 2009, 50 (7), pp.1110-5. ⟨10.2967/jnumed.108.059428⟩ |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.108.059428 |
| Popis: | This study was supported in part by the program of intellectual property management from the Canadian Institutes of Health Research, Ottawa, and by PulmoScience Inc., Montreal, Canada.; International audience; UNLABELLED: No test currently exists for molecular imaging of pulmonary arterial hypertension (PAH). Adrenomedullin is a vasodilator peptide predominantly cleared by pulmonary endothelial receptors. We developed a linear adrenomedullin derivative radiolabeled with (99m)Tc ((99m)Tc-AM-L) for imaging of pulmonary circulation and tested its capacity to detect anomalies of pulmonary circulation caused by PAH. METHODS: PAH was induced by monocrotaline in rats and compared with controls. After 5 wk, (99m)Tc-AM-L was injected intravenously. Plasma kinetics were measured, lung activity was determined in vivo after 30 min using a nuclear camera, and lung activity was determined ex vivo in explanted lungs. Expression of adrenomedullin receptors was measured in lung homogenates. RESULTS: The plasma levels of (99m)Tc-AM-L significantly increased in PAH by approximately 2-fold. Uptake by the lungs was homogeneous but greatly reduced in PAH by about 70%. In vivo retention was 14% +/- 1% (mean +/- SD) of the injected dose in controls and 4% +/- 1% in PAH (P < 0.0001). A similar reduction was measured ex vivo (6.0 +/- 1.6 percentage injected dose per gram [%ID/g] vs. 0.95 +/- 0.21 %ID/g, P < 0.0001). The expression of the heterodimeric component of the adrenomedullin receptor, receptor activity modifying protein 2, was also greatly reduced in PAH lungs (P < 0.001). Interestingly, right ventricular uptake of (99m)Tc-AM-L was increased by PAH (P = 0.02) and correlated with the degree of right ventricular hypertrophy (r = 0.83, P = 0.001). CONCLUSION: Pulmonary uptake of (99m)Tc-AM-L is greatly reduced in monocrotaline-induced PAH. This novel molecular imaging agent may be useful in the diagnosis and follow-up of pulmonary vascular disorders. |
| Databáze: | OpenAIRE |
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