Receptor imaging technique with 11C-labeled receptor ligands in living brain slices: Its application to time-resolved imaging and saturation analysis of benzodiazepine receptor using [11C]Ro15-1788

Tetsuhito Murata, Kiyoshi Matsumura, Hirotaka Onoe, Mats Bergström, Hajime Takechi, Sven Sihver, Wiebke Sihver, Henrik Neu, Yvonne Andersson, Mattias Ögren, Karl Johan Fasth, Bengt Långström, Yasuyoshi Watanabe

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Abstract

Recently we developed a novel imaging technique using positron emitter-labeled compounds as probes and a storage phosphor screen as a detector. This approach makes it possible to follow a variety of biochemical processes with spatial information in living brain slices. Further technical development is reported here in terms of time-resolved imaging and receptor characterization in a real equilibrium state. The method was validated by use of [11C]Ro15-1788, a benzodiazepine receptor antagonist. Fresh brain slices were incubated with [11C]Ro15-1788 in oxygenated Krebs-Ringer solution at 37°C, in a specially designed chamber. By placing the chamber on a storage phosphor screen, we could obtain two-dimensional images of radioactivity in the slices. Time-resolved imaging was made at 5 min intervals, revealing that it took 60 min to reach equilibrium binding. The dissociation process was observed by adding an excess amount of unlabeled Ro15-1788 to the chamber, 25 min was required for the full dissociation. In the equilibrium state, i.e. in the presence of free radio-ligand, Scatchard plot analysis was performed on the cerebral cortex (K(d) = 7.4 nM, B(max) = 146 fmol/mg tissue) and striatum (K(d) = 7.5 nM, B(max) = 107 fmol/mg tissue), suggesting the presence of a single component of binding site in these two regions. The present method, for the first time, made it possible to study a ligand-receptor interaction in living brain slices with temporal and spatial resolutions. This technique should prove useful for studies of receptor function under physiological conditions.

Original languageEnglish
Pages (from-to)145-154
Number of pages10
JournalNeuroscience Research
Volume25
Issue number2
DOIs
Publication statusPublished - 06-1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Murata, T., Matsumura, K., Onoe, H., Bergström, M., Takechi, H., Sihver, S., Sihver, W., Neu, H., Andersson, Y., Ögren, M., Fasth, K. J., Långström, B., & Watanabe, Y. (1996). Receptor imaging technique with 11C-labeled receptor ligands in living brain slices: Its application to time-resolved imaging and saturation analysis of benzodiazepine receptor using [11C]Ro15-1788. Neuroscience Research, 25(2), 145-154. https://doi.org/10.1016/S0168-0102(96)01037-1