The assessment of dopamine release with the PET competition model is thoroughly validated but entails disadvantages for the investigation of cognitive processes. We introduce a novel approach incorporating 6-[¹⁸F]FDOPA uptake as index of the dynamic regulation of dopamine synthesis enzymes by neuronal firing. The feasibility of this approach is demonstrated by assessing widely described sex differences in dopamine neurotransmission. Reward processing was behaviorally investigated in 36 healthy participants, of whom 16 completed fPET and fMRI during the monetary incentive delay task. A single 50 min fPET acquisition with 6-[¹⁸F]FDOPA served to quantify task-specific changes in dopamine synthesis. In men monetary gain induced stronger increases in ventral striatum dopamine synthesis than loss. Interestingly, the opposite effect was discovered in women. These changes were further associated with reward (men) and punishment sensitivity (women). As expected, fMRI showed robust task-specific neuronal activation but no sex difference. Our findings provide a neurobiological basis for known behavioral sex differences in reward and punishment processing, with important implications in psychiatric disorders showing sex-specific prevalence, altered reward processing and dopamine signaling. The high temporal resolution and magnitude of task-specific changes make fPET a promising tool to investigate functional neurotransmitter dynamics during cognitive processing and in brain disorders.

使用 PET 竞争模型对多巴胺释放的评估已得到彻底验证，但对认知过程的调查有不利之处。我们介绍了一种新方法，将 6-[ ¹⁸ F]FDOPA 摄取作为神经元放电对多巴胺合成酶的动态调节的指标。通过评估广泛描述的多巴胺神经传递中的性别差异，证明了这种方法的可行性。在 36 名健康参与者中对奖励处理进行了行为调查，其中 16 名在金钱奖励延迟任务期间完成了 fPET 和 fMRI。一次 50 分钟 fPET 采集，使用 6-[ ¹⁸F]FDOPA 用于量化多巴胺合成中特定任务的变化。在男性中，金钱收益导致腹侧纹状体多巴胺合成的增加比损失更大。有趣的是，在女性身上发现了相反的效果。这些变化进一步与奖励（男性）和惩罚敏感性（女性）相关。正如预期的那样，功能磁共振成像显示出强大的任务特异性神经元激活，但没有性别差异。我们的研究结果为奖励和惩罚处理中已知的行为性别差异提供了神经生物学基础，对表现出性别特异性患病率、改变的奖励处理和多巴胺信号传导的精神疾病具有重要意义。