RT Journal Article
SR Electronic
T1 Molecular Imaging of Monocrotaline-Induced Pulmonary Vascular Disease with Radiolabeled Linear Adrenomedullin
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1110
OP 1115
DO 10.2967/jnumed.108.059428
VO 50
IS 7
A1 Dupuis, Jocelyn
A1 Harel, François
A1 Fu, Yan
A1 Nguyen, Quang Trinh
A1 Letourneau, Myriam
A1 Préfontaine, Annick
A1 Fournier, Alain
YR 2009
UL http://jnm.snmjournals.org/content/50/7/1110.abstract
AB 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.