研究目的
To evaluate the in vivo binding specificity of [18F]MA3, a CB2 receptor agonist radiotracer, in a rat model with local overexpression of human CB2R and in a healthy non-human primate using PET imaging.
研究成果
The evaluation demonstrated that [18F]MA3 shows specific and reversible binding to hCB2R in a rat model, indicating its potential for imaging the active state of CB2 receptors with PET. However, in a healthy non-human primate, no specific binding was observed, likely due to low CB2R expression. The mutated AAV rat model is useful for evaluating both agonist and inverse agonist tracers. Further clinical studies in patients with neuroinflammation are recommended.
研究不足
The study has limitations including small sample sizes (n=3 for rats, n=1 for monkey) which preclude statistical analysis, rapid metabolism of the tracer in non-human primates, and inability to observe specific binding in healthy monkey brain due to low CB2R expression. Autoradiography protocols for spleen were suboptimal, and there may be minor CB1 receptor binding.
1：Experimental Design and Method Selection:
The study involved the synthesis and evaluation of [18F]MA3, a radiotracer for PET imaging of CB2 receptors. Methods included radiosynthesis, in vivo PET imaging in rat and non-human primate models, ex vivo autoradiography, and plasma radiometabolite analysis.
2：Sample Selection and Data Sources:
Rats with local overexpression of hCB2R in the striatum (n=3 for PET studies, n=1 for autoradiography) and a female rhesus monkey (n=1) were used. Data were acquired from PET scans and autoradiography.
3：List of Experimental Equipment and Materials:
Equipment included a Focus? 220 PET scanner, HPLC systems (Shimadzu LC-2010A HT), gamma counters (Wallac 1480 Wizard), cryotome (Shandon cryotome FSE), and phosphor storage screens (Perkin Elmer). Materials included chemicals from Aldrich, TCI Europe, Acros, and specific compounds like NE40 and Rimonabant.
4：Experimental Procedures and Operational Workflow:
Radiosynthesis of [18F]MA3 was performed. PET scans were conducted under anesthesia with dynamic acquisition and reconstruction. Blocking and displacement studies used NE40 or Rimonabant. Ex vivo autoradiography involved sacrificing rats, freezing brains, sectioning, and exposure to phosphor screens. Plasma metabolite analysis involved blood sampling, centrifugation, HPLC, and radioactivity counting.
5：Data Analysis Methods:
Data were analyzed using PMOD software for time-activity curves and binding potential calculations. Statistical analysis was not performed due to small sample sizes; data are expressed as mean ± SD.
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