Cardiac Magnetic Resonance Feature Tracking Analysis for Change in Right Ventricular Function After Cardioplegic Arrest.

BACKGROUND: Using echocardiography to assess right ventricular (RV) function after cardioplegic arrest is challenging. Cardiac magnetic resonance (CMR) imaging is a superior alternative, with the feature tracking technique enabling quantitative assessment of myocardial deformation. METHODS: This single-center, prospective study from 2020 to 2022 assessed RV function in 42 patients who underwent open heart surgery with cardioplegic arrest. CMR data were collected preoperatively, one week postoperatively, and at follow-up (6-12 months after surgery), and assessed using the CMR feature tracking technique. RESULTS: Postoperatively, there was no significant change in RV end-diastolic volume, but RV end-systolic volume significantly decreased, leading to a notable increase in RV ejection fraction. By follow-up, both RV end-diastolic and end-systolic volumes had significantly reduced compared with the preoperative values. Right ventricular longitudinal contractility decreased after surgery but recovered to the preoperative values by follow-up, while RV circumferential contractility improved postoperatively and remained superior to the preoperative levels at follow-up. CONCLUSION: On CMR imaging, significant changes in RV systolic motion were observed after cardioplegic arrest, with decreased longitudinal but increased circumferential contractility. At follow up, these changes had reverted to the preoperative patterns by the mid-term (6-12 months).

Relationship between assistant's lens exposure and dose information during computed tomography examinations.

According to International Commission of Radiological Protection, the equivalent dose limit for the eye lens for occupational exposure is recommended to be 20 mSv yr-1, averaged over 5 years, with no single year above 50 mSv. Some studies reported the measurement of assistant's lens exposure in diagnostic computed tomography (CT) examinations, but further investigation is still required in the association between the lens dose for assistants and various dose parameters. Therefore, we measured the assistant's lens exposure using small optically stimulated luminescence dosimeters. The type of occupation, type of assistance, total scan time, total mAs, total scan length, and dose-length product (DLP) were recorded and analyzed in association with air kerma at the lens position. The assistance was classified into four types: 'assisted ventilation,' 'head holding,' 'body holding,' and 'raising patient's arm.' The air kerma of lens position was not significantly different for each assistance type (p< 0.05, Kruskal-Wallis test). Further, the lens doses for assistants correlated with DLP, but with various strengths of correlation with the assistance type and were influenced by the distance from the CT gantry. In conclusion, lens dose during assistance and DLP demonstrated the strongest correlation. 'Raising patient's arm' and 'head holding' exhibited stronger correlations, which required less table movement during the CT scan than 'assisted ventilation' and 'body holding'.

Structural Dissection of Epsin-1 N-Terminal Helical Peptide: The Role of Hydrophobic Residues in Modulating Membrane Curvature.

Spatiotemporal structural alterations in cellular membranes are the hallmark of many vital processes. In these cellular events, the induction of local changes in membrane curvature often plays a pivotal role. Many amphiphilic peptides are able to modulate membrane curvature, but there is little information on specific structural factors that direct the curvature change. Epsin-1 is a representative protein thought to initiate invagination of the plasma membrane upon clathrin-coated vesicles formation. Its N-terminal helical segment (EpN18) plays a key role in inducing positive membrane curvature. This study aimed to elucidate the essential structural features of EpN18 in order to better understand general curvature-inducing mechanisms, and to design effective tools for rationally controlling membrane curvature. Structural dissection of peptides derived from EpN18 revealed the decisive contribution of hydrophobic residues to (i) enhancing membrane interactions, (ii) helix structuring, (iii) inducing positive membrane curvature, and (iv) loosening lipid packing. The strongest effect was obtained by substitution with leucine residues, as this EpN18 analog showed a marked ability to promote the influx of octa-arginine cell-penetrating peptides into living cells.

Low serum pancreatic amylase levels as a novel latent risk factor for colorectal adenoma in non-alcohol drinkers.

BACKGROUND AND AIM: Obesity, insulin resistance, and metabolic alterations increase the risk of colorectal cancer and adenoma (CRA). Non-alcoholic fatty liver disease (NAFLD) or pancreatic disease (NAFPD) shares many risk factors with CRA that may have significant roles in its development; however, the relationship between CRA and NAFLD/NAFPD remains unclear. METHODS: This cross-sectional study recruited 712 eligible participants without current drinking who had undergone total colonoscopy as part of a health checkup. These participants were classified into a CRA group (n = 236) and a control group (n = 439), which consisted of individuals without CRA and a history of polyp resection. NAFLD and NAFPD were diagnosed based on abdominal ultrasonography findings. RESULTS: Non-alcoholic fatty liver disease was observed more frequently in individuals with CRA than in the control group (55.9% vs 41.6%, P < 0.01). There was no significant association between NAFPD and CRA; however, serum pancreatic amylase (P-amylase) levels were significantly lower in individuals with CRA. Although NAFLD was one of the factors increasing the presence of CRA (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.07-2.10), low P-amylase levels were significantly associated with the presence of CRA (OR, 1.73; 95% CI, 1.04-2.88) independent of age, sex, current smoking, obesity, metabolic alterations including insulin resistance, and NAFLD. CONCLUSIONS: Low serum P-amylase levels were a possible independent risk factor for CRA in the present study. The latent pancreatic exocrine-endocrine-gut relationship was considered a novel pathway involved in obesity-related CRA development, in non-alcoholic individuals.

Usefulness of a lead-acrylic shield for reducing lens dose of assistant in x-ray CT examination.

In computed tomography (CT) examinations, the usefulness of protective glasses for reducing lens exposure to assistants has been reported. The present study aimed to compare the dose reduction effect for assistants with lead-acrylic shields and protective glasses (0.07 mm Pb, 0.5 mm Pb) during CT examination. The air dose distribution in a CT examination room with and without a lead-acrylic shield was compared. It was found that the amount of scattered radiation was significantly reduced by installing a lead-acrylic shield at the CT gantry aperture. Moreover, the reduction rate of air kerma at the assistant's lens was higher using the lead acrylic shield than with the protective glasses-95.7% during head holding and 76.1% during assisted ventilation.

Clinical feasibility of single-shot fluid-attenuated inversion recovery with wide inversion recovery pulse designed to reduce cerebrospinal fluid and motion artifacts for evaluation of uncooperative patients in acute stroke protocol.

Fluid-attenuated inversion recovery (FLAIR) imaging is a key sequence for stroke assessment. Motion artifact reduction with short acquisition time is still challenging, but necessary in the magnetic resonance (MR) stroke protocol, especially for uncooperative patients suspected of stroke. The aim of this study is to investigate the feasibility of modified single-shot FLAIR with wide inversion recovery pulses for use in stroke patients. This is a prospective study, which included 30 patients clinically suspected of stroke who were examined by MR stroke protocol from January 2018 to September 2018. A 1.5 T, multi-shot-turbo spin-echo (TSE) conventional FLAIR, and single-shot-TSE-FLAIR with wide inversion recovery pulse were used. Modified single-shot FLAIR was obtained for 30 patients with suspected stroke who moved during conventional FLAIR scan. Motion artifacts were randomly and independently scored using a 5-grade scale by three radiologists in blinded fashion. Whether the FLAIR vessel hyperintensity sign was present was visually evaluated. Statistical tests included Wilcoxon-signed rank test and weighted Cohen's kappa statistics. The motion artifact score was significantly lower in single-shot FLAIR than in conventional FLAIR (0.37 ± 0.56 vs. 1.83 ± 1.18; p < 0.05. The vessel hyperintensity sign was visualized in 6 and 5 patients on single-shot and conventional FLAIR images, respectively. This study demonstrates the value of single-shot FLAIR for stroke assessment. Single-shot FLAIR reduced motion artifact and visualized vessel hyperintensity sign more than conventional FLAIR. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Membrane anchoring of a curvature-inducing peptide, EpN18, promotes membrane translocation of octaarginine.

EpN18 is a curvature-inducing peptide, which loosens lipid packing upon interaction with the cell membrane, and facilitates cell-membrane penetration by arginine-rich cell-penetrating peptides, including octaarginine (R8). In the present study, we conjugated the N-terminal of EpN18 with a pyrenebutyryl (pBu) moiety, which acts as an anchoring unit that increases membrane interactions. Enhanced lipid-packing loosening and cytosolic translocation of R8 were observed by the pBu anchoring of EpN18.

Enhancing the activity of membrane remodeling epsin-peptide by trimerization.

Modulating the structural dynamics of biomembranes by inducing bilayer curvature and lipid packing defects has been highlighted as a practical tool to modify membrane-dependent cellular processes. Previously, we have reported on an amphipathic helical peptide derived from the N-terminal segment (residues 1-18, EpN18) of epsin-1, which can promote membrane remodeling including lipid packing defects in cell membranes. However, a high concentration is required to exhibit a pronounced effect. In this study, we demonstrate a significant increase in the membrane-remodeling effect of EpN18 by constructing a branched EpN18 homotrimer. Both monomer and trimer could enhance cell internalization of octaarginine (R8), a cell-penetrating peptide. The EpN18 trimer, however, promoted the uptake of R8 at an 80-fold lower concentration than the monomer. Analysis of the generalized polarization of a polarity-sensitive dye (di-4-ANEPPDHQ) revealed a higher efficacy of trimeric EpN18 in loosening the lipid packing in the cell membrane. Circular dichroism measurements in the presence of lipid vesicles showed that the EpN18 trimer has a higher α-helix content compared with the monomer. The stronger ability of the EpN18 trimer to impede negative bilayer curvature is also corroborated by solid-state 31P NMR spectroscopy. Hence, trimerizing peptides can be considered a promising approach for an exponential enhancement of their membrane-remodeling performance.

Does the increased motion probing gradient directional diffusion tensor imaging of lumbar nerves using multi-band SENSE improve the visualization and accuracy of FA values?

PURPOSE: Diffusion tensor imaging (DTI) is useful to evaluate lumbar nerves visually and quantitatively. Multi-band sensitivity encoding (MB-SENSE) is a technique to reduce the scan time. This study aimed to investigate if super-multi-gradient DTI with multi-band sensitivity encoding (MB-SENSE) is better in evaluating lumbar nerves than the conventional method. METHODS: The participants were 12 healthy volunteers (mean age 33.6 years). In all subjects, DTI was performed using echo planar imaging with different motion probing gradient (MPG) directions (15 without MB, and 15, 32, 64, and 128 with MB) and the lumbar nerve roots were visualized with tractography. In the five groups, we evaluated the resultant DTI both visually and quantitatively. For visual measures, we counted the number of fluffs and disruptions of the nerve fibers. For quantitative measures, the fractional anisotropy (FA) and standard deviation of the fractional anisotropy (FA-SD) values at two regions (proximal and distal) of the lumbar nerve roots were quantified and compared. RESULTS: Among the five groups, the number of fluffs decreased as the number of MPG directions increased. However, the number of disruptions showed no significant differences. The FA-SD values decreased as the number of MPG directions increased, indicating that the signal variation was reduced with multi-gradient directional DTI. CONCLUSION: High-resolution multi-directional DTI with MB-SENSE may be useful to visualize nerve entrapments and may allow for more accurate DTI parameter quantification with opportunities for clinical diagnostic applications.

[Usefulness of a Contrast Dose Administration System Using the Radiology Information System].

We report on the construction of a system for managing prior information and injection condition used for contrast enhance CT examination using radiology information system (RIS). Contrast dose administration system using the RIS was possible to retrospectively investigate optimal injection conditions from the database. As the prior information, we designed the patient's profile information of the hospital information system (HIS) to reflect the patient's height, weight, and kidney function (eGFR, Cre), which is necessary information for contrast enhance CT examination, in the RIS. By adding E-Box (DICOM Gateway) to the injector, it became possible to reflect the amount of contrast agent used in patients and injection conditions at contrast enhance CT examination. The contrast agent use information is transmitted to RIS by using modality performed procedure step (MPPS). Database of injection condition at contrast enhance CT examination using the RIS, to determine the optimal injection conditions retrospectively. By utilizing the massive amount of clinical information stored in the RIS, the amount of contrast agent and injection condition at contrast enhance CT examination could be optimized. Reproducibility of the contrast effect can be secured. In the CE, evidence system linked with RIS, when considering the reproducibility at follow-up observation and comparative diagnosis in clinical practice, the contrast effect could be made constant. Contrast dose administration system using the RIS was useful.

Loosening of Lipid Packing by Cell-Surface Recruitment of Amphiphilic Peptides by Coiled-Coil Tethering.

Lipid packing has a strong influence on the formation and structural dynamics of cell membranes. Techniques to modulate lipid packing may thus enable modification of cellular functions and events. An 18-residue amphiphilic helical peptide derived from the N-terminal segment of epsin-1 (EpN18) is reported to induce positive membrane curvature and to loosen lipid packing in the cell membrane. In this study, it is shown that EpN18, crosslinked to a leucine-zipper peptide K4, is recruited to the cell surface by interacting with a cell-surface-expressed E3 leucine-zipper segment. Cell-surface tethering markedly enhanced loosening of lipid packing, which led to the promotion of membrane translocation of octaarginine. The loosening of lipid packing by EpN18 was also confirmed by analyzing the generalized polarization value with a membrane-environment-sensitive dye, 2-hydroxy-3-{2-[(2-hydroxyethyl)dimethylamino]ethyl}-4-{2-[6-(dibutylamino)-2-naphthyl]ethenyl}pyridiniumdibromide (di-4-ANEPPDHQ). This approach thus shows promise for the control of lipid packing and related cellular events.

Elucidating the rapid action of 2-(2-chlorophenyl)ethylbiguanide on HT-29 cells under a serum- and glucose-deprived condition.

We recently demonstrated the cytotoxic action of a novel phenformin derivative, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on HT-29 cells under a serum- and glucose-deprived condition. In that study, we showed that the ATF6 arm of the ER stress pathway and c-Myc expression were downregulated 12 h after the treatment with 2-Cl-Phen. Through characterization of intracellular events at the early phase of the 2-Cl-Phen treatment before noticeable morphological changes, we found rapid fluctuations in the c-Myc and ATF4 proteins but not in their mRNAs in 2-Cl-Phen-treated HT-29 cells under the serum- and glucose-deprived condition. The 2-Cl-Phen-mediated downregulation of ATF4 protein was not paralleled by the phosphorylation status of PERK and eIF2α. Reduction of c-Myc expression by 2-Cl-Phen was more profound than that of ATF4 expression, and phosphorylated c-Myc was downregulated within 2 h. Pharmacological studies on the expression of c-Myc and ATF4 proteins showed that this decrease was mediated through proteasomal degradation but not by autophagy. Interestingly, treatment with lithium chloride, which is a well-known inhibitor of GSK3ß, partially recovered the expression of ATF4 protein, but its effect on the level of total c-Myc protein was negligible. Treatment with 2-Cl-Phen increased the expression of phosphorylated AMPK, but Compound C, an AMPK inhibitor, did not influence the expression of c-Myc protein in HT-29 cells. Finally, we observed that 2-Cl-Phen partially attenuated the gene expression of integrin subunit α1 (ITGA1), a downstream target of c-Myc. Taken together, these results show that 2-Cl-Phen rapidly downregulated the expression of c-Myc in addition to ER stress responses in a post-translational manner. Further elucidation and improvement of this multi-target-directed compound will provide new insights for developing therapeutic strategies against cancer.

[Examination of Lower-extremity MRA Using Single-shot Balanced SSFP with Saturation Recovery].

Currently, non-contrast angiography using the balanced steady-state free precession (b-SSFP) method, which uses a short scan time imaging method, has been reported as an alternative to lower-extremity MRA's conventional method. We investigated a new imaging method using balanced SSFP. This method uses a sequence of spectral attenuated inversion recovery (SPAIR) pulse for fat suppression, selective saturation pre-pulse for imaging range of background signal suppression, and rest slab on the downstream side of the imaging range for vein signal suppression. In the examination, we changed dummy pulse (0, 5, 10), saturation delay time (150 ms, 225 ms, 300 ms), and acquisition time (200 ms, 250 ms, 300 ms). For physical evaluation, we used the ROI method and for visual evaluation, we used the Scheffe's method. CR was the best and the visual evaluation was also good 10 for dummy pulse, a saturation delay time of 150 ms, and an acquisition time of 200 ms. Balanced SSFP with saturation recovery has the potential to shorten scanning times. Balanced SSFP with saturation recovery is useful for lower-extremity MRA.

Elucidation of a novel phenformin derivative on glucose-deprived stress responses in HT-29 cells.

Recently, we developed a variety of phenformin derivatives as selective antitumor agents. Based on previous findings, this study evaluated a promising compound, 2-(2-chlorophenyl)ethylbiguanide (2-Cl-Phen), on the basis of stress responses in the human colon cancer cell line HT-29 under a serum- and glucose-deprived condition. 2-Cl-Phen triggered morphological changes such as shrinkage and plasma membrane disintegration, as well as a decrease in mitochondrial activity and an increase in LDH leakage. To understand intracellular issues relating to 2-Cl-Phen, this study focused on the expression levels of ER stress-inducible genes and several oncogenic genes. Serum and glucose deprivation significantly induced a variety of ER stress-inducible genes, but a 12-h treatment of 2-Cl-Phen down-regulated expression of several ER stress-related genes, with the exception of GADD153. Interestingly, the expression levels of ATF6α, GRP78, MANF, and CRELD2 mRNA were almost completely decreased by 2-Cl-Phen. This study also observed that a 24-h treatment of 2-Cl-Phen attenuated the expression levels of GRP78, GADD153, and c-Myc protein. The decrease in c-Myc protein occurred before the fluctuation of GRP78 protein, while the expression of c-Myc mRNA showed little change with cotreatment of serum and glucose deprivation with 2-Cl-Phen. To further understand the 2-Cl-Phen-induced down-regulation of ATF6-related genes, this study investigated the stability of ATF6α and GRP78 proteins using NanoLuc-tagged constructs. The expression levels of NanoLuc-tagged ATF6α and GRP78 were significantly down-regulated by 2-Cl-Phen in the presence or absence of the translation inhibitor cycloheximide. Taken together, our novel phenformin derivative 2-Cl-Phen has the unique characteristic of diminishing tumor adaptive responses, especially the expression of ATF6-related genes, as well as that of c-Myc protein, in a transcriptional and posttranscriptional manner under a serum- and glucose-deprived condition. Further characterization of cytotoxic mechanisms related to phenformin derivatives may give new insights into developing additional promising anticancer agents.

[Evaluation of Measurement Accuracy and Inter-institutional Comparison for Dose Calibrators].

PURPOSE: The aim of this study was to validate the reliability of dose calibrators for measuring the radioactivity of several radioisotopes in multi-institution. METHODS: We evaluated the measurement accuracy of dose calibrators using a commercially available source ((67) Ga, (99m) Tc, (123) I, (201) TL). Nine dose calibrators (five models) in seven institutions were performed in this study. Each source was measured at least 3 times a day over a period of 4 half-life. Linearity of concentration (%error value) and percent difference values (%diff measurement) between measured and estimated radioactivity were calculated to evaluate the measurement accuracy. In addition, difference among institutions (%diff institution) was evaluated by the error values between measured and reference institution values. RESULTS: Good linearity of concentration was found between measured and estimated radioactivity in (99m)Tc and (123)I. However, %error value was increased in (67)Ga and (201)TL (maximum 19.3%). %diff measurements were 1.9 ± 0.3% for (67)Ga, -0.9 ± 0.3% for (99m)Tc, 2.2 ± 0.4% for (123)I, and -0.7 ± 0.3% for (201)TL, respectively. Although there were no clear differences in six institutions, %diff institution in one institution tended to be higher than that obtained in other institutions. CONCLUSIONS: Our results indicated that measurement accuracy of nine dose calibrators (five models) was relatively stable. However, difference of measured values tended to be higher in a part of institution and source. It is important to perform quality assurance and quality control for dose calibrator using traceable source.

[Evaluation of optimal threshold of Z score map for statistical brain image analysis].

PURPOSE: Aim of this study was to investigate optimal threshold of Z score when evaluating statistics image of Alzheimer's disease visually. METHOD: We classified 53 clinical patients in control and target group, and evaluated the distribution of Z score calculated with statistical brain image analysis for magnetic resonance and perfusion single photon emission computed tomography (SPECT). The optimal Z score threshold was determined from statistical significance that compared previously mentioned groups. RESULTS: Target group was able to classify significantly Z score at 1.25 from control group in wide region of parietal lobe with statistical brain image analysis for perfusion SPECT. DISCUSSION: The optimal threshold is equal or less than 2.0, in the case of Z score variance is close to the standard normal distribution. In contrast, the threshold is over 2.0 in the case of Z score variance is more than 1.0, and then by using ordinary threshold 2.0, it cannot point out abnormality.

Strong Diagnostic Performance of Single Energy 256-row Multidetector Computed Tomography with Deep Learning Image Reconstruction in the Assessment of Myocardial Fibrosis.

Objective Although magnetic resonance imaging (MRI) is the gold standard for evaluating abnormal myocardial fibrosis and extracellular volume (ECV) of the left ventricular myocardium (LVM), a similar evaluation has recently become possible using computed tomography (CT). In this study, we investigated the diagnostic accuracy of a new 256-row multidetector CT with a low tube-voltage single energy scan and deep-learning-image reconstruction (DLIR) in detecting abnormal late enhancement (LE) in LVM. Methods We evaluated the diagnostic performance of CT for detecting LE in LVM and compared the results with those of MRI as a reference. We also measured the ECV of the LVM on CT and compared the results with those on MRI. Patients or Materials We analyzed 50 consecutive patients who underwent cardiac CT, including a late-phase scan and MRI, within three months of suspected cardiomyopathy. All patients underwent 256-slice CT (Revolution CT Apex; GE Healthcare) with a low tube-voltage (70 kV) single energy scan and DLIR for a late-phase scan. Results In patient- and segment-based analyses, the sensitivity, specificity, and accuracy of detection of LE on CT were 94% and 85%, 100% and 95%, and 96% and 93%, respectively. The ECV of LVM per patient on CT and MRI was 33.0% ±6.2% and 35.9% ±6.1%, respectively. These findings were extremely strongly correlated, with a correlation coefficient of 0.87 (p <0.0001). The effective radiation dose on late-phase scanning was 2.4±0.9 mSv. Conclusion The diagnostic performance of 256-row multislice CT with a low tube voltage and DLIR for detecting LE and measuring ECV in LVM is credible.

Clinical evaluation of 3D high-resolution isotropic knee MRI using Multi-Interleaved X-prepared TSE with inTUitive RElaxometry (MIXTURE) for simultaneous morphology and T2 mapping.

PURPOSE: Quantitative MRI techniques such as T2 mapping are useful in comprehensive evaluation of various pathologies of the knee joint yet require separate scans to conventional morphological measurements and long acquisition times. The recently introduced 3D MIXTURE (Multi-Interleaved X-prepared Turbo-Spin Echo with Intuitive Relaxometry) technique can obtain simultaneous morphologic and quantitative information of the knee joint. To compare MIXTURE with conventional methods and to identify differences in morphological and quantitative information. METHODS: Phantom studies were conducted, and in vivo human scans were performed (20 patients) presented with knee arthralgia. MIXTURE is based on 3D TSE without and with T2 preparation modules in an interleaved manner for both morphology with PDW and fat suppressed T2W imaging as well as quantitative T2 mapping within one single scan. Image quality and lesion depiction were visually assessed and compared between MIXTURE and conventional 2D TSE by two experienced radiologists. Contrast-to-noise ratio was used to assess the adjacent tissue contrast in a quantitative way for both obtained PDW and fat suppressed T2W images. Quantitative T2 values were measured in phantom and from in vivo knee cartilage. RESULTS: The overall diagnostic confidence and contrast-to-noise ratio were deemed comparable between MIXTURE and 2D TSE. While the chosen T2 preparation modules for MIXTURE rendered consistent T2 values comparing to the current standard, measured cartilage T2 values ranged from 26.1 to 50.7 ms, with significant difference between the lesion and normal areas (p < 0.05). CONCLUSIONS: MIXTURE can help to provide high-resolution information for both anatomical and pathological assessment.

A novel PET probe to selectively image heat shock protein 90α/ß isoforms in the brain.

BACKGROUND: Heat shock proteins (HSPs) are present throughout the brain. They function as molecular chaperones, meaning they help with the folding and unfolding of large protein complexes. These chaperones are vital in the development of neuropathological conditions such as Alzheimer's disease and Lewy body disease, with HSP90, a specific subtype of HSP, playing a key role. Many studies have shown that drugs that inhibit HSP90 activity have beneficial effects in the neurodegenerative diseases. Therefore, HSP90 PET imaging ligand can be used effectively to study HSP90 in neurodegenerative diseases. Among four HSP90 isoforms, two cytosolic isoforms (HSP90α and HSP90ß) thought to be involved in the structural homeostasis of the proteins related to the neurodegenerative diseases. Currently, no useful PET imaging ligands selectively targeting the two cytosolic isoforms of HSP90 have been available yet. RESULTS: In this study, we developed a novel positron emission tomography (PET) imaging ligand, [11C]BIIB021, by 11C-radiolabeling (a positron emitter with a half-life of 20.4 min) 6-Chloro-9-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-9H-purin-2-amine (BIIB021), an inhibitor with a high affinity for and selectivity to HSP90α and HSP90ß. [11C]BIIB021 was synthesized with a high yield, molar activity and radiochemical purity. [11C]BIIB021 showed a high binding affinity for rat brain homogenate as well as human recombinant HSP90α and HSP90ß proteins. Radioactivity was well detected in the rat brain (SUV 1.4). It showed clear specific binding in PET imaging of healthy rats and autoradiography of healthy rat and human brain sections. Radiometabolite was detected in the brain, however, total distribution volume was well quantified using dual-input graphical model. Inhibition of p-glycoprotein increased brain radioactivity concentrations. However, total distribution volume values with and without p-glycoprotein inhibition were nearly the same. CONCLUSIONS: We have developed a new PET imaging agent, [11C]BIIB021, specifically targeting HSP90α/ß. We have been successful in synthesizing [11C]BIIB021 and in vitro and in vivo imaging HSP90α/ß. However, the quantification of HSP90α/ß is complicated by the presence of radiometabolites in the brain and the potential to be a substrate for p-glycoprotein. Further efforts are needed to develop radioligand suitable for imaging of HSP90α/ß.