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The PET Radioligand [carbonyl-11C]Desmethyl-WAY-100635 Binds to 5-HT1A Receptors and Provides a Higher Radioactive Signal Than [carbonyl-11C]WAY-100635 in the Human Brain

Bengt Andrée, MD, PhD1, Christer Halldin, PhD1, Victor W. Pike, PhD2, Roger N. Gunn, PhD2, Hans Olsson, MD1 and Lars Farde, MD, PhD1

1 Psychiatry Section, Department of Clinical Neuroscience, Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden
2 MRC Cyclotron Unit, Hammersmith Hospital, Imperial College School of Medicine, London, United Kingdom



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  		FIGURE 1. Chemical structure of [carbonyl-11C]WAY-100635 (11C-WAY) and 2 metabolites, [carbonyl-11C]desmethyl-WAY-100635 (11C-DWAY) and [carbonyl-11C]cyclohexanecarboxylic acid.

 


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  		FIGURE 2. General compartmental configuration showing 2-CM and 3-CM.

 


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  		FIGURE 3. Time curves for regional brain radioactivity after intravenous injection of 11C-WAY (A) and 11C-DWAY (B), normalized to injected dose (300 MBq), and time curves for specific radioligand binding of 11C-WAY (C) and 11C-DWAY (D). dCb/dt indicates time of peak equilibrium.

 


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  		FIGURE 4. PET images in 3 projections of healthy male volunteer (subject 4), obtained by summation of frames acquired from 9 to 69 min after intravenous injection of 11C-WAY and 11C-DWAY, normalized to injected dose. Subject’s right is on left in transaxial and coronal projections. Anterior is on right in sagittal projection.

 


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  		FIGURE 5. (A) Mean (n = 5) 11C-WAY and 11C-DWAY plasma concentration, normalized to injected dose and corrected for metabolites, during 69-min interval after radioligand injection. (B) Time–activity curves for fraction of radioactivity in plasma represent unchanged 11C-WAY and 11C-DWAY.

 


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  		FIGURE 6. (A) Fitted regression lines for rate constants (K1, k2, k3, and k4) for 6 central 5-HT1A receptor-rich regions determined by kinetic 3-CM analysis for 11C-WAY (x-axis) and 11C-DWAY (y-axis) at a certain radioactivity concentration. (B) Corresponding fitted regression lines for rate constants (K1, k2, k5, and k6) in cerebellum.

 


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  		FIGURE 7. Fitted regression lines for regional BPs in 6 central regions in 5 healthy male volunteers calculated by kinetic 3-compartment analysis (BP3-CM), simplified reference tissue model (BPSRTM), and peak equilibrium method (BPEQ), respectively.

 




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