Characterization of patients with major psychiatric disorders with AMPA receptor positron emission tomography.

Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [11C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [11C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [11C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [11C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology.

Brain structures and functional connectivity in neglected children with no other types of maltreatment.

Child maltreatment can adversely affect brain development, leading to vulnerabilities in brain structure and function and various psychiatric disorders. Among the various types of child maltreatment, neglect has the highest incidence rate (76.0%); however, data on its sole adverse influence on the brain remain limited. This case-control brain magnetic resonance imaging (MRI) study identified the changes in gray matter structure and function that distinguish neglected children with no other type of maltreatment (Neglect group, n = 23) from typically developing children (TD group, n = 140), and investigated the association between these structural and functional differences and specific psychosocial phenotypes observed in neglected children. Our results showed that the Neglect group had a larger right and left anterior cingulate cortex (R/L.ACC) and smaller left angular gyrus (L.AG) gray matter volume. The larger R/L.ACC was associated with hyperactivity and inattention. Resting-state functional analysis showed increased functional connectivity (FC) between the left supramarginal gyrus (L.SMG) in the salience network (SN) and the right middle frontal gyrus (R.MFG) simultaneously with a decrease in FC with the L.ACC for the same seed. The increased FC for the R.MFG was associated with difficulty in peer problems and depressive symptoms; a mediating effect was evident for depressive symptoms. These results suggest that the structural atypicality of the R/L.ACC indirectly contributes to the disturbed FCs within the SN, thereby exacerbating depressive symptoms in neglected children. In conclusion, exposure to neglect in childhood may lead to maladaptive brain development, particularly neural changes associated with depressive symptoms.

18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging-Defined Extramural Venous Invasion Predicts Distant Metastasis and Reflects Strong Tumor Invasiveness in Rectal Cancer.

INTRODUCTION: Extramural vascular invasion in patients with rectal cancer is a poor prognostic factor associated with distant metastasis; thus, accurate preoperative diagnosis is important. However, the accurate detection of extramural vascular invasion using magnetic resonance imaging (MRI) is difficult, and an improved diagnostic modality is required. In addition, the factors involved in the formation of extramural venous invasion (EMVI) remain unclear. In this study, we aimed to examine the ability of 18F-fluorodeoxyglucose positron emission tomography/MRI ([18F] FDG PET/MRI) to detect EMVI and elucidate the factors involved in EMVI. METHODS: Thirty-one patients with rectal cancer were enrolled in this study between 2017 and 2021. We preoperatively evaluated the pelvic [18F] FDG PET/MRI to detect extramural vascular invasion ([18F] FDG PET/MRI-defined EMVI: pmrEMVI). To investigate the factors related to pmrEMVI, we confirmed the desmoplastic reaction (DR) and TWIST expression in the primary lesions of rectal cancer and examined its relationship with pmrEMVI. RESULTS: Six of the 31 patients were pmrEMVI positive. Four pmrEMVI-positive patients had distant metastases. The levels of immature DR and TWIST1 expression were significantly higher in cases with pmrEMVI positivity. CONCLUSION: pmrEMVI is a useful biomarker for predicting distant metastasis. In addition, pmrEMVI was significantly correlated with factors related to tumor invasiveness.

Effects of functional polymorphisms of opioid receptor mu 1 and catechol-O-methyltransferase on the neural processing of pain.

AIM: Pain is reconstructed by brain activities and its subjectivity comes from an interplay of multiple factors. The current study aims to understand the contribution of genetic factors to the neural processing of pain. Focusing on the single-nucleotide polymorphism (SNP) of opioid receptor mu 1 (OPRM1) A118G (rs1799971) and catechol-O-methyltransferase (COMT) val158met (rs4680), we investigated how the two pain genes affect pain processing. METHOD: We integrated a genetic approach with functional neuroimaging. We extracted genomic DNA information from saliva samples to genotype the SNP of OPRM1 and COMT. We used a percept-related model, in which two different levels of perceived pain intensities ("low pain: mildly painful" vs "high pain: severely painful") were employed as experimental stimuli. RESULTS: Low pain involves a broader network relative to high pain. The distinct effects of pain genes were observed depending on the perceived pain intensity. The effects of low pain were found in supramarginal gyrus, angular gyrus, and anterior cingulate cortex (ACC) for OPRM1 and in middle temporal gyrus for COMT. For high pain, OPRM1 affected the insula and cerebellum, while COMT affected the middle occipital gyrus and ACC. CONCLUSION: OPRM1 primarily affects sensory and cognitive components of pain processing, while COMT mainly influences emotional aspects of pain processing. The interaction of the two pain genes was associated with neural patterns coding for high pain and neural activation in the ACC in response to pain. The proteins encoded by the OPRM1 and COMT may contribute to the firing of pain-related neurons in the human ACC, a critical center for subjective pain experience.

Regional cortical hypoperfusion and atrophy correlate with striatal dopaminergic loss in Parkinson's disease: a study using arterial spin labeling MR perfusion.

PURPOSE: To investigate the relationship of the striatal dopamine transporter density to changes in the gray matter (GM) volume and cerebral perfusion in patients with Parkinson's disease (PD). METHODS: We evaluated the regional cerebral blood flow (CBF) and GM volume, concurrently measured using arterial spin labeling and T1-weighted magnetic resonance imaging, respectively, as well as the striatal specific binding ratio (SBR) in 123I-N-ω-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)nortropane (123I-FP-CIT) single-photon emission computed tomography in 30 non-demented patients with PD (15 men and 15 women; mean age, 67.2 ± 8.8 years; mean Hoehn-Yahr stage, 2.2 ± 0.9). Voxel-wise regression analyses using statistical parametric mapping (SPM) were performed to explore the brain regions that showed correlations of the striatal SBR to the GM volume and CBF, respectively, with a height threshold of p < 0.0005 at the voxel level and p < 0.05 family-wise error-corrected at the cluster level. RESULTS: SPM analysis showed a significant positive correlation between the SBR and GM volume in the inferior frontal gyrus (IFG). Whereas, a positive correlation between the SBR and CBF was widely found in the frontotemporal and parietotemporal regions, including the IFG. Notably, the opercular part of the IFG showed significant correlations in both SPM analyses of the GM volume (r2 = 0.90, p < 0.0001) and CBF (r2 = 0.88, p < 0.0001). CONCLUSION: The voxel-wise analyses revealed the brain regions, mainly the IFG, that showed hypoperfusion and atrophy related to dopaminergic loss, which suggests that the progression of dopaminergic neurodegeneration leads to regional cortical dysfunction in PD.

The effects of epigenetic age and its acceleration on surface area, cortical thickness, and volume in young adults.

DNA methylation age has been used in recent studies as an epigenetic marker of accelerated cellular aging, whose contribution to the brain structural changes was lately acknowledged. We aimed to characterize the association of epigenetic age (i.e. estimated DNA methylation age) and its acceleration with surface area, cortical thickness, and volume in healthy young adults. Using the multi-tissue method (Horvath S. DNA methylation age of human tissues and cell types. 2013. Genome Biol 14), epigenetic age was computed with saliva sample. Epigenetic age acceleration was derived from residuals after adjusting epigenetic age for chronological age. Multiple regression models were computed for 148 brain regions for surface area, cortical thickness, and volume using epigenetic age or accelerated epigenetic age as a predictor and controlling for sex. Epigenetic age was associated with surface area reduction of the left insula. It was also associated with cortical thinning and volume reduction in multiple regions, with prominent changes of cortical thickness in the left temporal regions and of volume in the bilateral orbital gyri. Finally, accelerated epigenetic age was negatively associated with right cuneus gyrus volume. Our findings suggest that understanding the mechanisms of epigenetic age acceleration in young individuals may yield valuable insights into the relationship between epigenetic aging and the cortical change and on the early development of neurocognitive pathology among young adults.

Feasibility of [18F]FDG PET/MRI with Early-Delayed and Extended PET as One-Stop Imaging for Staging and Predicting Metastasis in Rectal Cancer.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/magnetic resonance imaging ([18F]FDG PET/MRI) for preoperative staging and usefulness of the detection of extramural vascular invasion (EMVI) for predicting metastasis in rectal cancer. METHODS: Twenty-three patients underwent pretreatment [18F]FDG PET/MRI, including early-delayed and extended PET and dedicated pelvic MRI without using anticonvulsant or contrast agents. Seven patients received preoperative treatment and all subsequently underwent surgery. Clinical cancer stages were evaluated using postoperative histopathology as a reference. PET/MR-defined EMVI (pmrEMVI) and pathological (p) TN stages were correlated with disease progression for a maximum of 2 years. RESULTS: Of 16 patients without preoperative treatment, 10 had pT3, 4 tumors, 7 had pN1-3 lymph nodes, and 5 had synchronous metastases (SM; liver, lung, inguinal node). The sensitivity, specificity, and accuracy of PET/MRI were 90%, 67%, and 81% for T staging (T1, 2 vs. T3, 4), and 89%, 100%, and 94% for N staging (N0 vs. N1-3), respectively. Patient-based accuracy for SM staging was 100% (4/4). Of 23 patients, 6 were positive for pmrEMVI and 4 had metachronous metastases or local recurrence (MM; pelvic node, brain, lung, skin) during the follow-up periods. Five of the 6 pmrEMVI-positive patients had SM and/or MM (odds ratio = 37.5). Among pT, pN, and pmrEMVI, pmrEMVI-positivity was the only significant predictor for poorer progression-free survival (p < 0.05). CONCLUSIONS: [18F]FDG PET/MRI according to our suggested protocol is a one-stop, non-contrast, and valid diagnostic method for rectal cancer staging, and pmr-EMVI can be used as an imaging biomarker for predicting metastases.

Arterial spin labeling imaging for the detection of cerebral blood flow asymmetry in patients with corticobasal syndrome.

PURPOSE: Corticobasal syndrome (CBS) and Parkinson's disease (PD) both present with asymmetrical extrapyramidal symptoms, often leading to a diagnostic dilemma. Patients with CBS frequently show cerebral blood flow (CBF) asymmetry alongside asymmetrical cortical atrophy. This study aimed to evaluate the clinical utility of arterial spin labeling (ASL) magnetic resonance imaging (MRI) to detect CBF asymmetry in patients with CBS. METHODS: We retrospectively investigated asymmetries of regional CBF and cortical volume, measured using ASL and T1-weighted MRI, in 13 patients with CBS and 22 age-matched patients with PD. Regional CBF and cortical volume values were derived from nine brain regions on each side. CBF and volume asymmetries were calculated as %difference in each region, respectively. RESULTS: CBF asymmetry showed significantly greater differences in seven of nine regions, such as the perirolandic area (- 8.7% vs. - 1.4%, p < 0.001) and parietal cortex (- 9.7% vs. - 1.3%, p < 0.001) in patients with CBS compared with patients with PD. In contrast, significant differences in volume asymmetry were observed in three regions included within the seven regions showing CBF asymmetry, which indicated that CBF asymmetry has greater sensitivity than volume asymmetry to detect asymmetricity in CBS. CONCLUSION: ASL imaging showed significant CBF asymmetry in a wider range of brain regions in patients with CBS, which suggests that noninvasive MRI with ASL imaging is a promising tool for the diagnosis of CBS, with advantages that include the simultaneous evaluation of asymmetrical hypoperfusion in addition to focal atrophy.

Development of Low Molecular Weight Ligands for Integrin αvß3.

We designed and synthesized non-peptide organic molecular ligands for integrin αvß3. Candidate ligands featured amidino analog and carboxy groups as binding sites on either side of a spacer, which consisted of benzophenone or an analog, such as diphenyl sulfide, diphenyl sulfoxide, diphenyl sulfone, or diphenyl ether. Competitive binding assays to integrin αvß3 with respect to [125I]echistatin were used to determine inhibitory activity of the synthetic ligands. Ligands bearing 2-aminobenzimidazoyl and glycyl groups separated by a benzophenone spacer demonstrated more potent binding than did a linear Arg-Gly-Asp (RGD) tripeptide that represents the native integrin αvß3 binding motif. Ligands possessing 2-aminobenzimidazoyl and carboxy groups and diphenyl sulfoxide or diphenyl ether spacers inhibited binding of [125I]echistatin with IC50 values similar to that of the linear RGD tripeptide.

Quantification of brain oxygen extraction and metabolism with [15O]-gas PET: A technical review in the era of PET/MRI.

Oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2) are key cerebral physiological parameters to identify at-risk cerebrovascular patients and understand brain health and function. PET imaging with [15O]-oxygen tracers, either through continuous or bolus inhalation, provides non-invasive assessment of OEF and CMRO2. Numerous tracer delivery, PET acquisition, and kinetic modeling approaches have been adopted to map brain oxygenation. The purpose of this technical review is to critically evaluate different methods for [15O]-gas PET and its impact on the accuracy and reproducibility of OEF and CMRO2 measurements. We perform a meta-analysis of brain oxygenation PET studies in healthy volunteers and compare between continuous and bolus inhalation techniques. We also describe OEF metrics that have been used to detect hemodynamic impairment in cerebrovascular disease. For these patients, advanced techniques to accelerate the PET scans and potential synthesis with MRI to avoid arterial blood sampling would facilitate broader use of [15O]-oxygen PET for brain physiological assessment.

The vertebral 3'-deoxy-3'-18F-fluorothymidine uptake predicts the hematological toxicity after systemic chemotherapy in patients with lung cancer.

OBJECTIVES: Although hematological toxicities (HT) are the leading adverse events of systemic chemotherapy, the estimation of severe HT is challenging. Recently, 3'-deoxy-3'-[18F]-fluorothymidine (18F-FLT) accumulation with PET has been considered a biomarker of the cell proliferation. This study aims to elucidate whether the vertebral accumulation of 18F-FLT could estimate severe HT during platinum-doublet chemotherapy. METHODS: In this Institutional Review Board-approved retrospective study, 50 patients with primary lung cancer underwent 18F-FLT PET scan before platinum-doublet chemotherapy. We evaluated the standardized uptake value, total vertebral proliferation (TVP), and TVP/body surface area (TVP/BSA) of the vertebral body (Th4, Th8, Th12, and L4), and then the associations between those parameters and frequency of severe HT during platinum-doublet chemotherapy were assessed. RESULTS: Severe HT (grade 3/4) was observed in 40.0% of patients during the first cycle. The ROC curve analyses revealed that the TVP/BSA of L4 was the most discriminative parameter among PET parameters for the prediction of severe HT. The multivariate logistic regression analysis revealed the TVP/BSA of L4 (odds ratio [OR], 0.94; p = 0.0036) and the frequency of the grade 3/4 hematological toxicity in previous clinical trials (OR, 1.03; p = 0.023) were independent predictors. Furthermore, the sensitivity, specificity, and accuracy of the TVP/BSA of L4 cut-off of 68.7 to predict grade 3/4 HT were 80.0%, 86.7%, and 84.0%, respectively. A low TVP/BSA of L4 (< 68.7) as a binary variable was a significant indicator of severe HT (OR, 26.0; p = 0.000026). CONCLUSIONS: The low 18F-FLT uptake in the lower vertebral body is a predictor of severe HT in patients with lung cancer who receive platinum-doublet chemotherapy. TRIAL REGISTRATION: Trial registration: UMIN000027540 KEY POINTS: • The vertebral 18 F-FLT uptake with PET is an independent predictor of the severe hematological toxicity during the first cycle of platinum-doublet chemotherapy. • The 18 F-FLT uptake in L4 vertebral body estimated hematological toxicities better than that in the upper vertebra (Th4, Th8, and Th12). • The evaluation of the amount and activity of hematopoietic cells in the bone marrow cavity using 18 F-FLT PET imaging could provide predictive data of severe hematological toxicities and help determine an appropriate drug combination or dose intensity in patients with advanced malignant diseases.

Self-Face Recognition Begins to Share Active Region in Right Inferior Parietal Lobule with Proprioceptive Illusion During Adolescence.

We recently reported that right-side dominance of the inferior parietal lobule (IPL) in self-body recognition (proprioceptive illusion) task emerges during adolescence in typical human development. Here, we extend this finding by demonstrating that functional lateralization to the right IPL also develops during adolescence in another self-body (specifically a self-face) recognition task. We collected functional magnetic resonance imaging (fMRI) data from 60 right-handed healthy children (8-11 years), adolescents (12-15 years), and adults (18-23 years; 20 per group) while they judged whether a presented face was their own (Self) or that of somebody else (Other). We also analyzed fMRI data collected while they performed proprioceptive illusion task. All participants performed self-face recognition with high accuracy. Among brain regions where self-face-related activity (Self vs. Other) developed, only right IPL activity developed predominantly for self-face processing, with no substantial involvement in other-face processing. Adult-like right-dominant use of IPL emerged during adolescence, but was not yet present in childhood. Adult-like common activation between the tasks also emerged during adolescence. Adolescents showing stronger right-lateralized IPL activity during illusion also showed this during self-face recognition. Our results suggest the importance of the right IPL in neuronal processing of information associated with one's own body in typically developing humans.

PET probe detecting non-small cell lung cancer susceptible to epidermal growth factor receptor tyrosine kinase inhibitor therapy.

Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR-TKIs) are used as molecular targeted therapy for non-small cell lung cancer (NSCLC) patients. The therapy is applied to the patients having EGFR-primary L858R mutation, but drug tolerance caused by EGFR-secondary mutation is occurred within one and half years. For the non-invasive detection of the EGFR-TKIs treatment positive patients by positron emission tomograpy (PET) imagaing, fluorine-18 labeled thienopyrimidine derivative, [18F]FTP2 was newly synthesized. EGFR inhibition assay, cell uptake study, and blocking study indicated [18F]FTP2 binds with high and selective affinity for EGFR with L858R mutation, and not with L858R/T790M dual mutations. On animal PET study using tumor bearing mice, H3255 cells expressing L858R mutated EGFR was more clearly visualized than H1975 cells expressing L858R/T790M dual mutated EGFR. [18F]FTP2 has potential for detecting NSCLC which is susceptible to EGFR-TKI treatment.

Development of Right-hemispheric Dominance of Inferior Parietal Lobule in Proprioceptive Illusion Task.

Functional lateralization can be an indicator of brain maturation. We have consistently shown that, in the adult brain, proprioceptive processing of muscle spindle afferents generating illusory movement of the right hand activates inferior frontoparietal cortical regions in a right-side dominant manner in addition to the cerebrocerebellar motor network. Here we provide novel evidence regarding the development of the right-dominant use of the inferior frontoparietal cortical regions in humans using this task. We studied brain activity using functional magnetic resonance imaging while 60 right-handed blindfolded healthy children (8-11 years), adolescents (12-15 years), and young adults (18-23 years) (20 per group) experienced the illusion. Adult-like right-dominant use of the inferior parietal lobule (IPL) was observed in adolescents, while children used the IPL bilaterally. In contrast, adult-like lateralized cerebrocerebellar motor activation patterns were already observable in children. The right-side dominance progresses during adolescence along with the suppression of the left-sided IPL activity that emerges during childhood. Therefore, the neuronal processing implemented in the adult's right IPL during the proprioceptive illusion task is likely mediated bilaterally during childhood, and then becomes right-lateralized during adolescence at a substantially later time than the lateralized use of the cerebrocerebellar motor system for kinesthetic processing.

Highly Sensitive Telomerase Assay Insusceptible to Telomerase and Polymerase Chain Reaction Inhibitors for Cervical Cancer Screening Using Scraped Cells.

A sensitive telomerase assay based on asymmetric-polymerase chain reaction (A-PCR) on magnetic beads and subsequent application of cycling probe technology, STAMC, which is insusceptible to DNase and PCR inhibitors, was for the first time applied to clinical specimens in addition to a conventional telomeric repetitive amplification protocol (TRAP). The electrophoresis results showed that an increase in scraped cervical cancer cells not only reduced TRAP products but also increased smaller products, suggesting the unreliability of TRAP for clinical samples. To achieve the required sensitivity of STAMC for clinical application, the sequence and concentration conditions were explored for the forward and reverse primers for A-PCR, which resulted in a detection limit of only two HeLa cells with 1 µM TS primer (5'-AATCCGTCGAGCAGAGTT-3') and 0.04 µM ACX primer (5'-GCGCGGCTTACCCTTACCCTTACCCTAACC-3'). Under the same primer conditions, the fluorescence signal of STAMC increased as scraped cervical cancer cells increased despite showing a negligible intensity for benign tumors. Furthermore, STAMC showed no signal for a cervical cancer patient treated with irradiation therapy. These results indicate that STAMC is useful for not only cervical cancer screening but also investigating the effect of cancer treatments such as radiation therapy and drug administration.

Impaired myocardial microcirculation in the flow-glucose metabolism mismatch regions in revascularized acute myocardial infarction.

BACKGROUND: In successfully revascularized acute myocardial infarction (AMI), microvascular function in a myocardial flow-glucose metabolism mismatch pattern has not been reported. We aimed to elucidate myocardial flow reserve (MFR) and myocardial viability in mismatch segments. METHODS: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and adenosine stress 13N-ammonia PET were performed in eighteen AMI patients to evaluate myocardial glucose metabolism, myocardial blood flow (MBF), and MFR. Infarct segments were classified into 3 groups: normal (preserved resting MBF), mismatch (preserved FDG uptake but reduced resting MBF), and match (reduced FDG uptake and resting MBF). Regional wall motion score (WMS) was assessed immediately after reperfusion and recovery periods. RESULTS: MFR in the mismatch group was significantly lower than that in non-infarct-related segments (1.655 ± 0.516 vs 2.282 ± 0.629, P < .01) and similar to that in the match group (1.635 ± 0.528, P = .999). WMS in the mismatch group was significantly improved (3.07 ± 0.48 vs 2.07 ± 1.14, P = .003); however, in recovery periods, WMS in the mismatch group was significantly higher than that in the normal group (1.05 ± 1.04, P < .01). CONCLUSIONS: In successfully revascularized AMI, microvascular function is impaired despite preserved myocardial glucose metabolism in mismatch segments.

Precise Evaluation of Striatal Oxidative Stress Corrected for Severity of Dopaminergic Neuronal Degeneration in Patients with Parkinson's Disease: A Study with 62Cu-ATSM PET and 123I-FP-CIT SPECT.

BACKGROUND: This study sought to precisely evaluate striatal oxidative stress and its relationship with the disease severity in Parkinson's disease (PD) using double brain imaging, 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) (62Cu-ATSM) PET and 123I-FP-CIT SPECT. METHODS: Nine PD patients were studied with brain 62Cu-ATSM PET for oxidative stress and 123I-FP-CIT SPECT for the density of striatal dopamine transporter. Standardized uptake values (SUVs) were obtained from the delayed phase of dynamic 62Cu-ATSM PET, and striatum-to-cerebellum SUV ratio (SUVR) was calculated. To correct the effect of neuronal loss in the striatum, 62Cu-ATSM SUVR was corrected for striatal specific binding ratio (SBR) values of 123I-FP-CIT (SUVR/SBR). RESULTS: 62Cu-ATSM SUVR without correction was not significantly correlated with disease severity estimated by the Unified Parkinson's Disease Rating Scale (UPDRS) scores or 123I-FP-CIT SBR. In contrast, the SUVR/SBR showed significant correlations with the UPDRS total and motor scores, and 123I-FP-CIT SBR. CONCLUSION: Oxidative stress in the remaining striatal dopaminergic neurons estimated by SUVR/SBR was increased with disease severity in PD patients, suggesting that oxidative stress based on mitochondrial dysfunction contributes to promoting dopaminergic neuronal degeneration in PD. 62Cu-ATSM PET with 123I-FP-CIT SPECT correction would be a promising tool to evaluate dopaminergic neuronal oxidative stress in PD.

The 38th Report on Survey of the Adverse Reaction to Radiopharmaceuticals (The 41st Survey in 2015).

This survey was performed to investigate the incidence of adverse reactions to radiopharmaceuticals in FY2015 in Japan. It was based on the responses to questionnaires sent to nuclear medicine institutions. The reply was obtained from 981 institutions among 1,274 to which the questionnaire had been sent. Fifteen cases of adverse reactions were reported. A total of 1,056,828 radiopharmaceutical administrations were reported. The incidence of adverse reactions per 100,000 cases was 1.4. No case of deficient products was reported.