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Evaluation of the putative dopamine D₃ PET tracer [¹¹C]WC-10 in non-human primates

¹ Diagnostic Radiology, Yale School of Medicine, New Haven, Connecticut; ² GlaxoSmithKline Imaging Center & Imperial College, London, United Kingdom; ³ Washington University, St. Louis, Missouri

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Objectives: [¹¹C]WC-10, a dopamine D₃ antagonist with high binding affinity in vitro, has been reported to be a putative imaging agent for the D₃ receptor (Mach et al: JNM 2006, 47:27p). We evaluated this tracer in non-human primates to assess its ability to image D₃ receptors in vivo.

Methods: Radiolabeling was performed with [¹¹C]methyl iodide on the AutoLoop module. PET scans were conducted on the HRRT in Rhesus monkeys. Two 120 min dynamic scans were acquired for each monkey: one control scan followed by a blocking scan with the selective D₃ antagonist SB-277011. The same scan protocol was then repeated with [¹¹C]PHNO, a D₃-preferring tracer.

Results: [¹¹C]WC-10 was prepared in 132 ± 32 mCi yield (beam condition: 55µA, 32 ± 6 min) at end of synthesis (n = 7). Radiochemical and chemical purities were 98%, with specific activity of 4.4 ± 1.1 Ci/µmol at the time of injection. In the control scans, heterogeneous distribution of activity was observed in the monkey brain, with the highest uptake in the cingulate cortex, followed by putamen, caudate (CD), thalamus (TH), frontal cortex, and globus pallidus (GP), and lowest uptake in the occipital cortex and cerebellum. Regional binding potential (BP) values from equilibrium data were < 0.4. With SB-277011, no reduction of BP was seen in any of the D₃-rich brain regions. In contrast, when the monkeys were treated with SB-277011 and scanned with [¹¹C]PHNO, BP were reduced by 25, 45, and 66% in the CD, GP, and TH, respectively.

Conclusions: Evaluation of [¹¹C]WC-10 in vivo indicated that it does not possess the right properties as a PET tracer for imaging the dopamine D₃ receptor in the monkey brain.

Research Support: GSK

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nabulsi, N. Articles by Huang, Y. PubMed Articles by Nabulsi, N. Articles by Huang, Y.