Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [¹¹C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA). However, the availability of [¹¹C]metomidate is limited to centers with an on-site cyclotron. Here, we report an early-phase human study with the ¹⁸F-labeled analog, para-chloro-2-[¹⁸F]fluoroethyletomidate ([¹⁸F]CETO). Methods: We conducted a phase I/IIa, single-center, open-label, microdosing study. The primary objective was to evaluate the safety of up to 2 administrations of [¹⁸F]CETO in 6 patients with PA (3 unilateral disease, 3 bilateral disease) and 5 healthy volunteers. Safety evaluation included assessment of adrenal function after the first [¹⁸F]CETO administration. The biodistribution of [¹⁸F]CETO was assessed in a 90-min dynamic PET acquisition. In patients with PA, the effect of pretreatment with oral dexamethasone on [¹⁸F]CETO uptake by normal adrenal tissue and APAs was also assessed. Results: Eleven participants were recruited to the trial, including 6 patients and 5 healthy volunteers. No subjects experienced serious adverse events or reactions, and all participants had normal adrenal function after [¹⁸F]CETO administration. [¹⁸F]CETO demonstrated high selectivity for the adrenal glands with low uptake in other tissues. Visualization of APAs was enhanced after dexamethasone pretreatment, which suppressed [¹⁸F]CETO uptake by normal adrenal tissue. Conclusion: [¹⁸F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this study. [¹⁸F]CETO demonstrates selective high affinity for adrenal tissue, particularly APAs. Distinction between APAs and normal adrenal tissue is enhanced by dexamethasone pretreatment to suppress [¹⁸F]CETO uptake by normal glands. This positions [¹⁸F]CETO as a promising imaging tool for evaluation in the context of PA.

Cognitive flexibility is the ability to appropriately adapt one's thinking and behavior to changing environmental demands and is conceptualized as an aspect of executive function. The dopamine system has been implicated in cognitive flexibility; however, a direct, that is, neurochemical, link to cognitive flexibility has not been shown yet. The aim of this study was, therefore, to investigate how cognitive flexibility is mediated by dopaminergic signaling in the ventromedial prefrontal cortex (vmPFC). Methods: Eighteen participants were measured in a PET study with 174 ± 12 MBq of the D_2/3 receptor ligand [¹⁸F]fallypride in a block design with 2 parts. While participants processed 2 tasks sequentially without rule switching on a computer screen in the first part of the PET scan, they had to flexibly switch between the 2 task rules after 100 min after injection in the second part. Dopamine release (γ) was quantified using the linearized simplified reference region model contrasting the 2 task blocks (switching vs. no-switching/baseline). Results: The statistical analysis of the parametric γ-images showed that the increased cognitive demand during task switching induced a displacement of the D_2/3 receptor ligand [¹⁸F]fallypride in the vmPFC (maximum T value = 13.8; cluster size: 528 voxels; familywise error rate-corrected P < 0.001; mean γ = 0.022 ± 0.006 min^-1). Furthermore, a correlation between behavioral switch costs and vmPFC [¹⁸F]fallypride displacement suggested that participants showing greater dopamine release were more efficient in task switching. Conclusion: To our knowledge, this is the first experimental PET study to show direct involvement of dopamine in the vmPFC in a task-switching paradigm, confirming model assumptions about the neurochemical basis of cognitive flexibility.