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The Potential of a Radiosensitive Intracerebral Probe to Monitor ¹⁸F-MPPF Binding in Mouse Hippocampus In Vivo

¹ IMNC, UMR8165 CNRS-Université of Paris 7 and Paris 11, Orsay, France; ² LEDI, IRSN, BP17, 92262 Fontenay aux Roses, France ; ³ Laboratory of Neuropharmacology FRE CNRS 3006, University of Lyon, and CERMEP-Biomedical Cyclotron, Lyon, France; and ⁴ MIRCen, URA CEA-CNRS 2210, Orsay, France

Correspondence: For correspondence or reprints contact: Philippe Laniece, Laboratoire Imagerie et Modélisation en Neurobiologie et Cancérologie, CNRS UMR8165, Université Paris-Sud, 91406 Orsay Cedex, France. E-mail: laniece{at}imnc.in2p3.fr

As mouse imaging has become more challenging in preclinical research, efforts have been made to develop dedicated PET systems. Although these systems are currently used for the study of physiopathologic murine models, they present some drawbacks for brain studies, including a low temporal resolution that limits the pharmacokinetic study of radiotracers. The aim of this study was to demonstrate the ability of a radiosensitive intracerebral probe to measure the binding of a radiotracer in the mouse brain in vivo. Methods: The potential of a probe 0.25 mm in diameter for pharmacokinetic studies was assessed. First, Monte Carlo simulations followed by experimental studies were used to evaluate the detection volume and sensitivity of the probe and its adequacy for the size of loci in the mouse brain. Second, ex vivo autoradiography of 5-hydroxytryptamine receptor 1A (5-HT_1A) receptors in the mouse brain was performed with the PET radiotracer 2'-methoxyphenyl-(N-2'-pyridinyl)-p-¹⁸F-fluorobenzamidoethylpiperazine (¹⁸F-MPPF). Finally, the binding kinetics of ¹⁸F-MPPF were measured in vivo in both the hippocampus and the cerebellum of mice. Results: Both the simulations and the experimental studies demonstrated the feasibility of using small probes to measure radioactive concentrations in specific regions of the mouse brain. Ex vivo autoradiography showed a heterogeneous distribution of ¹⁸F-MPPF consistent with the known distribution of 5-HT_1A in the mouse brain. Finally, the time–activity curves obtained in vivo were reproducible and validated the capacity of the new probe to accurately measure ¹⁸F-MPPF kinetics in the mouse hippocampus. Conclusion: Our results demonstrate the ability of the tested radiosensitive intracerebral probe to monitor binding of PET radiotracers in anesthetized mice in vivo, with high temporal resolution suited for compartmental modeling.

Key Words: β microprobe • mouse • ¹⁸F-MPPF • 5-HT_1A receptors • small-animal imaging

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