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

Journal of Nuclear Medicine

Frédéric Pain¹  Thierry Delzescaux¹  Aurélie Desbrée¹  Laurent Pinot¹  Albertine Dubois¹  Mathieu Verdurand¹  Hirac Gurden¹  Roland Mastrippolito¹  Philippe Lanièce¹  Luc Zimmer¹  Jeremy Godart¹ 

关键词: β microprobe;    mouse;    ¹⁸F-MPPF;    5-HT_1A receptors;    small-animal imaging;   

DOI  :  10.2967/jnumed.107.050047

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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-HT1A) 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-HT1A 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.

【 授权许可】

Unknown