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Molecular Imaging of Monocrotaline-Induced Pulmonary Vascular Disease with Radiolabeled Linear Adrenomedullin

¹ Research Center, Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada; ² Department of Medicine, University of Montreal, Montreal, Quebec, Canada; ³ Department of Radiology, University of Montreal, Montreal, Quebec, Canada; and ⁴ Institut National de la Recherche Scientifique-Institut Armand Frappier, Laval, Quebec, Canada

Correspondence: For correspondence or reprints contact: Jocelyn Dupuis, Research Center, Montreal Heart Institute, 5000 Bélanger St., Montreal, Quebec, Canada, H1T 1C8. E-mail: jocelyn.dupuis{at}bellnet.ca

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 ^99mTc (^99mTc-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, ^99mTc-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 ^99mTc-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 ^99mTc-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 ^99mTc-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.

Key Words: diagnosis • pulmonary hypertension • imaging • lung • nuclear medicine

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JNM 2009 50: 11A-12A. [Full Text]