Test-retest reliability of C-ORM-13070 in PET imaging of α-adrenoceptors in vivo in the human brain.

Lehto, Jussi; Virta, Jere; Oikonen, Vesa; Roivainen, Anne; Luoto, Pauliina; Arponen, Eveliina; Helin, Semi; Hietamäki, Johanna; Holopainen, Aila; Kailajärvi, Marita; Peltonen, Juha; Rouru, Juha; Sallinen, Jukka; Virtanen, Kirsi; Volanen, Iina; Scheinin, Mika; Rinne, Juha

Purpose: α-Adrenoceptors share inhibitory presynaptic functions with the more abundant α-adrenoceptor subtype, but they also have widespread postsynaptic modulatory functions in the brain. Research on the noradrenergic system of the human brain has been hampered by the lack of suitable PET tracers targeted to the α-adrenoceptor subtypes. Methods: PET imaging with the specific α-adrenoceptor antagonist tracer [C]ORM-13070 was performed twice in six healthy male subjects to investigate the test-retest reliability of tracer binding. Results: The bound/free ratio of tracer uptake relative to nonspecific uptake into the cerebellum during the time interval of 5 - 30 min was most prominent in the dorsal striatum: 0.77 in the putamen and 0.58 in the caudate nucleus. Absolute test-retest variability in bound/free ratios of tracer ranged from 4.3 % in the putamen to 29 % in the hippocampus. Variability was also <10 % in the caudate nucleus and thalamus. Intraclass correlation coefficients (ICC) ranged from 0.50 in the hippocampus to 0.89 in the thalamus (ICC >0.70 was also reached in the caudate nucleus, putamen, lateral frontal cortex and parietal cortex). The pattern of [C]ORM-13070 binding, as determined by PET, was in good agreement with receptor density results previously derived from post-mortem autoradiography. PET data analysis results obtained with a compartmental model fit, the simplified reference tissue model and a graphical reference tissue analysis method were convergent with the tissue ratio method. Conclusion: The results of this study support the use of [C]ORM-13070 PET in the quantitative assessment of α-adrenoceptors in the human brain in vivo. Reliable assessment of specific tracer binding in the dorsal striatum is possible with the help of reference tissue ratios.

POSITRON emission tomography; ADRENERGIC receptors; INHIBITORY postsynaptic potential; NORADRENERGIC neurons; CAUDATE nucleus; THALAMUS; HIPPOCAMPUS (Brain)

European Journal of Nuclear Medicine & Molecular Imaging, 2015, Vol 42, Issue 1, p120

1619-7070

Academic Journal

10.1007/s00259-014-2899-z