RT Journal Article
SR Electronic
T1 Use of Adrenomedullin Derivatives for Molecular Imaging of Pulmonary Circulation
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1869
OP 1874
DO 10.2967/jnumed.108.054023
VO 49
IS 11
A1 François Harel
A1 Yan Fu
A1 Quang Trinh Nguyen
A1 Myriam Letourneau
A1 Louis P. Perrault
A1 Alexandre Caron
A1 Alain Fournier
A1 Jocelyn Dupuis
YR 2008
UL http://jnm.snmjournals.org/content/49/11/1869.abstract
AB Currently, there is no low-molecular-weight agent for imaging of the pulmonary circulation. Adrenomedullin (AM) is a peptide predominantly cleared by the pulmonary circulation through specific endothelial receptors. We developed human AM derivatives radiolabeled with 99mTc and evaluated their biodistribution, plasma kinetics, and utility as pulmonary vascular imaging agents. Methods: Two derivatives radiolabeled with 99mTc were evaluated: the natural cyclic form of the peptide, to which the chelator diethylenetriaminepentaacetic acid was added (C-DTPA-AM), and the linear form, which allows direct labeling (L-AM). The compounds were injected into dogs, and the activities of the tracers in blood and in organs were determined with a nuclear medicine camera. Single-pass pulmonary clearance was measured by the indicator dilution technique. The capacity to image perfusion defects was evaluated after surgical pulmonary artery ligation. Results: Both derivatives were rapidly cleared from plasma, with elimination half-lives of 42 and 32 min for C-DTPA-AM and L-AM, respectively. The lungs retained most of the activity after 30 min; this activity was higher (P = 0.02) for L-AM (42% ± 5% [mean ± SEM]) than for C-DTPA-AM (27% ± 1%). Lung activity slowly declined over time but was maintained after 2 h at approximately 20% for both tracers. The single-pass pulmonary clearance of plasma L-AM was 414 ± 85 mL/min. There was a higher level of urinary excretion of L-AM than of C-DTPA-AM. After pulmonary artery ligation, perfusion defects were easily detectable by external imaging. Conclusion: AM derivatives are promising compounds for molecular imaging of the pulmonary circulation. L-AM displayed higher levels of initial lung retention and of kidney excretion.