Visualization Of Ampa Receptors In Patients With Schizophrenia And Depression: The First Pet Imaging Study

Abstract Background Evidence on physiological roles of AMPA receptors in psychiatric conditions, including schizophrenia, has been accumulated, which mainly derives from psychiatric disease model animals as well as post-mortem brain tissues. However, its clinical translation was limited due to lack of any tool to visualize AMPA receptors in living human brain. We have recently developed a new positron emission tomography (PET) probe for AMPA receptors (Miyazaki et al. Nature Medicine, in press). Here, we used the first PET probe that specifically binds to AMPA receptors and successfully visualized these receptors in living human brain of patients with schizophrenia. Methods We developed a novel PET probe for AMPARs, named [11C]K-2 (Miyazaki et al. Nature Medicine, in press). Male patients aged 30–49 with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) underwent a [11C]K-2 PET scan and an MRI scan for co-registration of the PET image and received clinical assessments for symptomatology, including the Positive and Negative Syndrome Scale (PANSS) (registration number: UMIN000025132). [11C]K-2 was synthesized at Yokohama City University Hospital in accordance with GMP ordinance and was certified by the Japanese Society of Nuclear Medicine. PET imaging was performed with a TOSHIBA Aquiduo scanner (TOSHIBA Medical), which provided an axial FOV of 240 mm, and 80 contiguous 2.0 mm thick slices. Standardized uptake value ratio (SUVR)30–50 min with the whole brain and white matter as a reference was calculated, respectively. Results Ten subjects with schizophrenia (mean±SD age, 43.1±3.1 years; duration of illness, 16.8±8.0 years; PANSS total score, 61.7±13.4) participated in this study. There were negative correlations between SUVR30-50 min with the whole brain as a reference in the cingulate gyrus and parahippocampus and PANSS total scores according to the voxel-wise analysis. These correlations were not observed when the while matter was used as a reference. Discussion [11C]K-2 has revealed distinct distribution patterns of AMPA receptors for schizophrenia. Thus, [11C]K-2 is proven to be a potent PET tracer that can be used to visualize AMPARs with high contrast, leading to the elucidation of the molecular mechanisms of schizophrenia.