Detection of α2-Adrenergic Receptors in Brain of Living Pig with 11C-Yohimbine

Journal of Nuclear Medicine

Steen Jakobsen¹  Svend B. Jensen¹  Paul Cumming¹  Donald F. Smith¹  Kasper Pedersen¹  Ole L. Munk¹ 

关键词: adrenergic;    receptors;    yohimbine;    RX821002;    PET;    receptor binding;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

There have been few radiotracers for imaging adrenergic receptors in brain by PET, but none has advanced for use in human studies. We developed a radiosynthesis for the α2-adrenergic antagonist 11C-yohimbine and characterized its binding in living pigs. As a prelude to human studies with 11C-yohimbine, we determined the whole-body distribution of 11C-yohimbine and calculated its dosimetry. Methods: Yorkshire × Landrace pigs weighing 35–40 kg were used in the study. Baseline and postchallenge PET recordings of 11C-yohimbine in pig brain were conducted for 90 min, concurrent with arterial blood sampling, and with yohimbine and RX821002 as pharmacologic interventions. 15O-Water scans were performed to detect changes in cerebral perfusion. The PET images were manually coregistered to an MR atlas of the pig brain. Maps of the 11C-yohimbine distribution volume ([Vd] mL g−1) in brain were calculated relative to the arterial input function. Results: Whole-body scans with 11C-yohimbine revealed high accumulation of radioactivity in kidney, intestine, liver, and bone. The estimated human dose was 5.6 mSv/GBq, a level commonly accepted in human PET studies. Brain imaging showed baseline values of Vd ranging from 1.9 in medulla, 3.0 in cerebellum, and to 4.0 in frontal cortex. Coinjection with nonradioactive yohimbine (0.07 mg/kg) reduced Vd globally to approximately 1.5–2 mL g−1. A higher yohimbine dose (1.6 mg/kg) was without further effect on self-displacement. Very similar results were obtained by displacement with the more selective α2-adrenergic antagonist RX821002 at doses of 0.15 and 0.7 mg/kg. Cerebral blood flow was globally increased 43% after administration of RX821002. Notable features of 11C-yohimbine are a lack of plasma metabolism over 90 min and a rapid approach to equilibrium binding in brain. Conclusion: The new radiotracer 11C-yohimbine seems well suited for PET investigations of α2-adrenergic receptors in brain and peripheral structures, with the caveat that displaceable binding was present in cerebellum and throughout the brain.

【 授权许可】

Unknown