PET imaging of 11C-labeled thiamine tetrahydrofurfuryl disulfide, vitamin B1 derivative: First-in-human study.

Vitamine B1 thiamine is an essential component for glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is more absorbent compared to readily-available water-soluble thiamine salts since it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions were not clarified yet. Recently, 11C-labeled thiamine and TTFD were synthesized by our group, and their pharmacokinetics were investigated by PET imaging in normal rats. In this study, to clarify the whole body pharmacokinetics of [11C]TTFD in human healthy volunteers, we performed first-in-human PET imaging study with [11C]TTFD, along with radiation dosimetry of [11C]TTFD in humans. METHODS: Synthesis of [11C]TTFD was improved for clinical study. Dynamic whole-body PET images were acquired on three young male normal subjects after intravenous injection of [11C]TTFD. VOIs were defined for source organs on the PET images to measure time-course of [11C]TTFD uptake as percentage injected dose and the number of disintegrations for each organ. Radiation dosimetry was calculated with OLINDA/EXM. RESULTS: We succeeded in developing the improved synthetic method of [11C]TTFD for the first-in-human PET study. In the whole body imaging, uptake of [11C]TTFD by various tissues was almost plateaued at 10 min after intravenous injection, afterward gradually increased for the brain and urinary bladder (urine). %Injected dose was high in the liver, kidney, urinary bladder, heart, spine, brain, spleen, pancreas, stomach, and salivary glands, in this order. %Injected dose per gram of tissue was high also in the pituitary. By dosimetry, the effective radiation dose of [11C]TTFD calculated was 5.5 µSv/MBq (range 5.2-5.7). CONCLUSION: Novel synthetic method enabled clinical PET study with [11C]TTFD, which is a safe PET tracer with a dosimetry profile comparable to other common 11C-PET tracers. Pharmacokinetics of TTFD in the pharmacological dose and at different nutritional states could be further investigated by future quantitative PET studies. Noninvasive in vivo PET imaging for pathophysiology of thiamine-related function may provide diagnostic evidence of novel information about vitamin B1 deficiency in human tissues.

Japanese and North American Alzheimer's Disease Neuroimaging Initiative studies: Harmonization for international trials.

INTRODUCTION: We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America. METHODS: A total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography- or cerebrospinal fluid amyloid ß(1-42)-positive LMCI and mild AD between J-ADNI and ADNI. RESULTS: Amyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J-ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid-positive LMCI in J-ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J-ADNI (n = 73) compared with ADNI (n = 230). DISCUSSION: These results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries.

Inter-rater variability of visual interpretation and comparison with quantitative evaluation of 11C-PiB PET amyloid images of the Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) multicenter study.

PURPOSE: The aim of this study was to assess the inter-rater variability of the visual interpretation of 11C-PiB PET images regarding the positivity/negativity of amyloid deposition that were obtained in a multicenter clinical research project, Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI). The results of visual interpretation were also compared with a semi-automatic quantitative analysis using mean cortical standardized uptake value ratio to the cerebellar cortex (mcSUVR). METHODS: A total of 162 11C-PiB PET scans, including 45 mild Alzheimer's disease, 60 mild cognitive impairment, and 57 normal cognitive control cases that had been acquired as J-ADNI baseline scans were analyzed. Based on visual interpretation by three independent raters followed by consensus read, each case was classified into positive, equivocal, and negative deposition (ternary criteria) and further dichotomized by merging the former two (binary criteria). RESULTS: Complete agreement of visual interpretation by the three raters was observed for 91.3% of the cases (Cohen κ = 0.88 on average) in ternary criteria and for 92.3% (κ = 0.89) in binary criteria. Cases that were interpreted as visually positive in the consensus read showed significantly higher mcSUVR than those visually negative (2.21 ± 0.37 vs. 1.27 ± 0.09, p < 0.001), and positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. Significant positive/negative associations were observed between mcSUVR and the number of raters who evaluated as positive (ρ = 0.87, p < 0.0001) and negative (ρ = -0.85, p < 0.0001) interpretation. Cases of disagreement among raters showed generally low mcSUVR. CONCLUSIONS: Inter-rater agreement was almost perfect in 11C-PiB PET scans. Positive or negative decision by visual interpretation was dichotomized by a cut-off value of mcSUVR = 1.5. As some cases of disagreement among raters tended to show low mcSUVR, referring to quantitative method may facilitate correct diagnosis when evaluating images of low amyloid deposition.

Technical Considerations on Scanning and Image Analysis for Amyloid PET in Dementia.

Brain imaging techniques, such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET), can provide essential and objective information for the early and differential diagnosis of dementia. Amyloid PET is especially useful to evaluate the amyloid-ß pathological process as a biomarker of Alzheimer's disease. This article reviews critical points about technical considerations on the scanning and image analysis methods for amyloid PET. Each amyloid PET agent has its own proper administration instructions and recommended uptake time, scan duration, and the method of image display and interpretation. In addition, we have introduced general scanning information, including subject positioning, reconstruction parameters, and quantitative and statistical image analysis. We believe that this article could make amyloid PET a more reliable tool in clinical study and practice.

Ethnic comparison of pharmacokinetics of (18)F-florbetaben, a PET tracer for beta-amyloid imaging, in healthy Caucasian and Japanese subjects.

PURPOSE: (18)F-Florbetaben is a positron emission tomography (PET) tracer indicated for imaging cerebral beta-amyloid deposition in adult patients with cognitive impairment who are being evaluated for Alzheimer's disease and other causes of cognitive decline. The present study examined ethnic comparability of the plasma pharmacokinetics, which is the input to the brain, between Caucasian and Japanese subjects. METHODS: Two identical phase I trials were performed in 18 German and 18 Japanese healthy volunteers to evaluate the plasma pharmacokinetics of a single dose of 300 MBq (18)F-florbetaben, either of low (≤5 µg, LD) or high (50-55 µg, HD) mass dose. Pharmacokinetic parameters were evaluated based on the total (18)F radioactivity measurements in plasma followed by metabolite analysis using radio-HPLC. RESULTS: The pharmacokinetics of (18)F-florbetaben was characterized by a rapid elimination from plasma. The dose-normalized areas under the curve of (18)F-florbetaben in plasma as an indicator of the input to the brain were comparable between Germans (LD: 0.38 min/l, HD: 0.55 min/l) and Japanese (LD: 0.35 min/l, HD: 0.45 min/l) suggesting ethnic similarity, and the mass dose effect was minimal. A polar metabolite fraction was the main radiolabelled degradation product in plasma and was also similar between the doses and the ethnic groups. CONCLUSION: Absence of a difference in the pharmacokinetics of (18)F-florbetaben in Germans and Japanese has warranted further global development of the PET imaging agent.

[Harmonization of Standardized Uptake Value among Different Generation PET/ CT Cameras Based on a Phantom Experiment -Utility of SUV(peak)].

Standardized uptake value (SUV) has been widely used as a semi-quantitative metric of uptake in FDGPET/ CT for diagnosis of malignant tumors and evaluation of tumor therapies. However, the SUV depends on various factors including PET/CT scanner specifications and reconstruction parameters. The purpose of this study is to harmonize the SUV among two PET/CT models of different generation: two units of Discovery ST Elite Performance(DSTEP) and Discovery 690 (D690) PET/CT scanners. The NEMA body phantom filled with 18F solution was scanned for 30 minutes in list-mode. The D690 PET images were reconstructed with OSEM, OSEM+TOF, and OSEM+PSF. Gaussian post-filters of 4-9 mm FWHM were applied to find the parameters that provides harmonized SUV. We determined the SUV-harmonized parameter for each reconstruction algorithm. Then, the 10 PET images simulating clinical scan conditions were respectively generated to evaluate the bias and variability of SUV(max) and SUV(peak). The SUV(max) strongly depended not only on spatial resolution but also on image noise. On the other hand, the SUV(peak) was a robust metric to image noise level. TOF improved the variability of SUV(max) and SUV(peak). Thus, we were able to harmonize the spatial resolution using SUV(peak) based on the phantom study. Because SUV(max) was also strongly affected by image noise, sufficient count statistics is essential for SUV(max) harmonization. We recommended that TOF reconstruction and SUV(peak) metric should be used to harmonize SUV.

Improved Correlation of 18F-Flortaucipir PET SUVRs and Clinical Stages in the Alzheimer Disease Continuum with the MUBADA/PERSI-Based Analysis.

The Alzheimer disease (AD) continuum is a neurodegenerative disorder with cognitive decline and pathologic changes. Tau PET imaging can detect tau pathology, and 18F-flortaucipir PET imaging is expected to visualize progression through the stages of AD, for which quantitative assessment is essential. Two measurement methods, statistically defined multiblock barycentric discriminant analysis (MUBADA)/parametric estimation of reference signal intensity (PERSI) and anatomically defined tau meta-volume of interest (VOI)/cerebellar gray matter (CGM) for SUV ratio (SUVR), were compared in this study to assess their relationship to AD clinical stage using 2 open multicenter PET databases. Methods: Data were selected for 106 cases from 2 databases, AMED Preclinical AD study (AMED-PRE) (n = 15) and Alzheimer Disease Neuroimaging Initiative 3 (n = 91). The data of the participants were categorized into 4 groups based on the clinical criteria. Tau PET imaging was conducted using 18F-flortaucipir, and the 2 SUVR measurement methods, MUBADA/PERSI and tau meta-VOI/CGM, were compared among different clinical categories: amyloid-negative cognitively normal, preclinical AD, amyloid-negative mild cognitive impairment (MCI), and amyloid-positive MCI. Results: Significant differences were found between cognitively normal and preclinical AD, as well as between cognitively normal and amyloid-positive MCI and between amyloid-negative MCI and -positive MCI in SUVR derived by MUBADA/PERSI, whereas SUVR by tau meta-VOI/CGM did not provide significant differences between any pair. The tau meta-VOI/CGM method consistently provided higher SUVRs and larger individual variations than MUBADA/PERSI, with a mean SUVR difference of 0.136 for the studied databases. Conclusion: MUBADA/PERSI provided the SUVR of 18F-flortaucipir uptake with better association with the clinical severity of the AD continuum and with smaller variability. The results support the usefulness of MUBADA/PERSI as a quantitative measure of 18F-flortaucipir uptake in multicenter studies using different PET systems and scanning methods. However, limitations of the study include the small sample size and the unbalanced distribution among clinical categories in the AMED Preclinical AD study database.

Combining plasma Aß and p-tau217 improves detection of brain amyloid in non-demented elderly.

BACKGROUND: Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer's disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-ß (Aß)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aß-positron emission tomography (PET) in the preclinical and prodromal AD. METHODS: We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study. J-TRC included 474 non-demented individuals (CDR 0: 331, CDR 0.5: 143). Participants underwent plasma Aß and p-tau217 assessments, and Aß-PET imaging. Findings in J-TRC were replicated in the BioFINDER cohort including 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). In both cohorts, plasma Aß(1-42) (Aß42) and Aß(1-40) (Aß40) were measured using immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), and p-tau217 was measured with an immunoassay on the Meso Scale Discovery platform (Eli Lilly). RESULTS: Aß-PET was abnormal in 81 participants from J-TRC and 71 participants from BioFINDER. Plasma Aß42/Aß40 ratio and p-tau217 individually showed moderate to high accuracies when detecting abnormal Aß-PET scans, which were improved by combining plasma biomarkers and by including age, sex and APOE genotype in the models. In J-TRC, the highest AUCs were observed for the models combining p-tau217/Aß42 ratio, APOE, age, sex in the whole cohort (AUC = 0.936), combining p-tau217, Aß42/Aß40 ratio, APOE, age, sex in the CDR 0 group (AUC = 0.948), and combining p-tau217/Aß42 ratio, APOE, age, sex in the CDR 0.5 group (AUC = 0.955), respectively. Each subgroup results were replicated in BioFINDER, where the highest AUCs were seen for models combining p-tau217, Aß42/40 ratio, APOE, age, sex in cognitively unimpaired (AUC = 0.938), and p-tau217/Aß42 ratio, APOE, age, sex in mild cognitive impairment (AUC = 0.914). CONCLUSIONS: Combination of plasma Aß-related biomarkers and p-tau217 exhibits high performance when predicting Aß-PET positivity. Adding basic clinical information (i.e., age, sex, APOE Îµ genotype) improved the prediction in preclinical AD, but not in prodromal AD. Combination of Aß-related biomarkers and p-tau217 could be highly useful for pre-screening of participants in clinical trials of preclinical and prodromal AD.

Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with 68Ga-DOTA-octreotide: a potential PET tracer for beta cell mass measurement.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with (68)Gallium ((68)Ga). After intravenous injection of (68)Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that (68)Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of (68)Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with (68)Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

Dosimetry and efficacy of a tau PET tracer [18F]MK-6240 in Japanese healthy elderly and patients with Alzheimer's disease.

OBJECTIVE: A new tau PET tracer [18F]MK-6240 has been developed; however, its dosimetry and pharmacokinetics have been published only for a European population. This study investigated the safety, radiation dosimetry, pharmacokinetics and biodistribution of [18F]MK-6240 in Japanese elderly subjects. Also, the pattern and extent of brain retention of [18F]MK-6240 in Japanese healthy elderly subjects and patients with Alzheimer's disease (AD) were investigated. These Japanese results were compared with previous reports on non-Japanese. METHODS: Three healthy elderly subjects and three AD patients were enrolled. Dynamic whole-body PET scans were acquired for up to 232 min after starting injection of [18F]MK-6240 (370.4 ± 27.0 MBq) for the former, while a dynamic brain scan was performed from 0 to 75 min post injection for the latter. For both groups, brain PET scans were conducted from 90 to 110 min post injection. Sequential venous blood sampling was performed to measure the radioactivity concentration in the whole blood and plasma as well as the percentages of parent [18F]MK-6240 and radioactive metabolites in plasma. Organ doses and effective doses were estimated using the OLINDA Ver.2 software. Standardized uptake value ratios (SUVRs) and distribution volume ratios (DVRs) by Logan reference tissue model (LRTM) were measured in eight brain regions using the cerebellar cortex as the reference. Blood tests, urine analysis, vital signs and electrocardiography were performed for safety assessments. RESULTS: No adverse events were observed. The highest radiation doses were received by the gallbladder (257.7 ± 74.9 µGy/MBq) and the urinary bladder (127.3 ± 11.7 µGy/MBq). The effective dose was 26.8 ± 1.4 µSv/MBq. The parent form ([18F]MK-6240) was metabolized quickly and was less than 15% by 35 min post injection. While no obvious accumulation was found in the brain of healthy subjects, focal accumulation of [18F]MK-6240 was observed in the cerebral cortex of AD patients. Regional SUVRs of the focal lesions in AD patients increased gradually over time, and the difference of SUVRs between healthy subjects and AD patients became large and stable at 90 min after injection. High correlations of SUVR and DVR were observed (p < 0.01). CONCLUSION: The findings supported safety and efficacy of [18F]MK-6240 as a tau PET tracer for Japanese populations. Even though the number of subjects was limited, the radiation dosimetry profiles, pharmacokinetics, and biodistribution of [18F]MK-6240 were consistent with those for non-Japanese populations. TRIAL REGISTRATION: Japan Pharmaceutical Information Center ID, JapicCTI-194972.

Prognostic significance of SUVmax (maximum standardized uptake value) measured by [¹8F]FDG PET/CT in endometrial cancer.

PURPOSE: To determine if the preoperative maximum standardized uptake value (SUVmax) measured by [(18)F]FDG PET/CT has prognostic value in patients with endometrial cancer. METHODS: A total of 57 patients with FIGO stage I-IV endometrial cancer underwent FDG PET/CT imaging before radical surgery. SUVmax of the primary tumour was compared with histological prognostic factors, and the relationship between SUVmax and recurrence was examined. RESULTS: The median duration of follow-up was 33.1 months (range 4 to 68 months). SUVmax was significantly higher in patients with a higher FIGO stage (p = 0.0015), higher tumour histological grade (p < 0.0001), myometrial invasion (p = 0.0020), larger tumour size (p = 0.0056) and lymph node metastasis (p = 0.027). Univariate analysis showed that SUVmax (uncategorized value), FIGO stage, tumour histological grade, lymph node metastasis and lymphovascular space invasion were significantly associated with recurrence. However, multivariate analysis showed that only SUVmax (p = 0.045, hazard ratio 1.11, 95% CI 1.0028-1.231) was significantly associated with recurrence. Based on ROC curve analysis and log-rank tests, patients with a high a SUVmax (≥ 12.7) had a significantly lower disease-free survival rate than those with a low SUVmax (<12.7; p = 0.00042). CONCLUSION: Preoperative FDG uptake by the primary tumour is significantly associated with recurrence in patients with endometrial cancer.

New standards for phantom image quality and SUV harmonization range for multicenter oncology PET studies.

Not only visual interpretation for lesion detection, staging, and characterization, but also quantitative treatment response assessment are key roles for 18F-FDG PET in oncology. In multicenter oncology PET studies, image quality standardization and SUV harmonization are essential to obtain reliable study outcomes. Standards for image quality and SUV harmonization range should be regularly updated according to progress in scanner performance. Accordingly, the first aim of this study was to propose new image quality reference levels to ensure small lesion detectability. The second aim was to propose a new SUV harmonization range and an image noise criterion to minimize the inter-scanner and intra-scanner SUV variabilities. We collected a total of 37 patterns of images from 23 recent PET/CT scanner models using the NEMA NU2 image quality phantom. PET images with various acquisition durations of 30-300 s and 1800 s were analyzed visually and quantitatively to derive visual detectability scores of the 10-mm-diameter hot sphere, noise-equivalent count (NECphantom), 10-mm sphere contrast (QH,10 mm), background variability (N10 mm), contrast-to-noise ratio (QH,10 mm/N10 mm), image noise level (CVBG), and SUVmax and SUVpeak for hot spheres (10-37 mm diameters). We calculated a reference level for each image quality metric, so that the 10-mm sphere can be visually detected. The SUV harmonization range and the image noise criterion were proposed with consideration of overshoot due to point-spread function (PSF) reconstruction. We proposed image quality reference levels as follows: QH,10 mm/N10 mm ≥ 2.5 and CVBG ≤ 14.1%. The 10th-90th percentiles in the SUV distributions were defined as the new SUV harmonization range. CVBG ≤ 10% was proposed as the image noise criterion, because the intra-scanner SUV variability significantly depended on CVBG. We proposed new image quality reference levels to ensure small lesion detectability. A new SUV harmonization range (in which PSF reconstruction is applicable) and the image noise criterion were also proposed for minimizing the SUV variabilities. Our proposed new standards will facilitate image quality standardization and SUV harmonization of multicenter oncology PET studies. The reliability of multicenter oncology PET studies will be improved by satisfying the new standards.

Brain histamine H1 receptor occupancy of loratadine measured by positron emission topography: comparison of H1 receptor occupancy and proportional impairment ratio.

AIMS: We have evaluated the sedative properties of H1-antihistamines by using positron emission tomography (PET) and ¹¹C-doxepin. The purpose of the present study was to measure histamine H1 receptor occupancy (H1RO) of loratadine 10 mg in patients with allergic rhinitis and to compare this occupancy with that of d-chlorpheniramine 2 mg, a first-generation antihistamine. We also compared our PET findings with the proportional impairment ratio reported by McDonald et al. METHODS: The H1RO of loratadine 10 mg and d-chlorpheniramine 2 mg were evaluated in human brains in a double-blind and crossover design using ¹¹C-doxepin PET. Eleven young male patients with allergic rhinitis were examined by PET following oral single administration of loratadine 10 mg and d-chlorpheniramine 2 mg. RESULTS: Loratadine 10 mg occupied 11.7 ± 19.5% of histamine H1 receptors in the cortex, whereas d-chlorpheniramine 2 mg occupied 53.0 ± 33.2% in the same area, suggesting a non-sedating property of loratadine at a dose of 10 mg. The H1RO values of loratadine and d-chlorpheniramine as well as those of previous studies were found to be significantly proportional to the proportional impairment ratio (r = 0.899). CONCLUSION: Measurement of H1RO is a sensitive and absolute method to characterize the non-sedating property of drugs with H1 antagonistic activity.

FDG-PET/CT imaging of elastofibroma dorsi.

OBJECTIVE: The purpose of this study was to assess retrospectively the characteristics of FDG uptake in elastofibroma dorsi using integrated PET/CT. METHODS: From 10,261 oncology FDG-PET/CT scans performed over a 2-year period, findings suggestive of elastofiboma dorsi were observed in 46 FDG-PET/CT scans of 34 patients. As 20 patients had bilateral lesions and 14 had unilateral lesions, a total of 75 elastofibroma dorsi lesions on images were identified in this study. For visual analysis of intensity of FDG uptake , a four-point grading system was used: grade 0 for no uptake, grade 1 for less uptake than the liver, grade 2 for uptake comparable to the liver, and grade 3 for intense uptake greater than the liver. For quantitative analysis, the standardized uptake value (SUV) was calculated. The relationships between SUV and age, blood glucose level, lesion size, and related symptoms were also assessed. RESULTS: Among the 75 lesions, 4 had an uptake grade of 0, 41 had grade 1, 25 had grade 2, and 5 had grade 3. The mean SUV (±SD) of the 75 lesions was 2.0 ± 0.63 (range 0-5.1). The Pearson correlation coefficient test indicated a weak positive correlation between SUV and lesion size and no correlation between SUV and either age or blood glucose level. The SUVs of patients with symptoms due to the disease and patients without symptoms were almost the same. CONCLUSION: Mild and moderate uptake of FDG is frequently observed in elastofibroma dorsi, which should not be misinterpreted as abnormal accumulation observed in malignant lesions.

Clinical practice guidelines for high-resolution breast PET, 2019 edition.

Breast positron emission tomography (PET) has had insurance coverage when performed with conventional whole-body PET in Japan since 2013. Together with whole-body PET, accurate examination of breast cancer and diagnosis of metastatic disease are possible, and are expected to contribute significantly to its treatment planning. To facilitate a safer, smoother, and more appropriate examination, the Japanese Society of Nuclear Medicine published the first edition of practice guidelines for high-resolution breast PET in 2013. Subsequently, new types of breast PET have been developed and their clinical usefulness clarified. Therefore, the guidelines for breast PET were revised in 2019. This article updates readers as to what is new in the second edition. This edition supports two different types of breast PET depending on the placement of the detector: the opposite-type (positron emission mammography; PEM) and the ring-shaped type (dedicated breast PET; dbPET), providing an overview of these scanners and appropriate imaging methods, their clinical applications, and future prospects. The name "dedicated breast PET" from the first edition is widely used to refer to ring-shaped type breast PET. In this edition, "breast PET" has been defined as a term that refers to both opposite- and ring-shaped devices. Up-to-date breast PET practice guidelines would help provide useful information for evidence-based breast imaging.

Clinical impact of (11)C-methionine PET on expected management of patients with brain neoplasm.

PURPOSE: We retrospectively examined the clinical efficacy of (11)C-methionine positron emission tomography ((11)C-MET PET) in patients with brain neoplasm, especially whether the (11)C-MET PET changed the clinical management and whether the change was beneficial or detrimental. METHODS: This study reviewed 89 (11)C-MET PET scans for 80 patients (20 scans for initial diagnosis of brain tumor and 69 scans for differentiating tumor recurrence from radiation necrosis). Final diagnosis and the effect on the intended management were obtained from the questionnaire to the referring physicians or directly from the medical records. The diagnostic sensitivity, specificity, and accuracy for the (11)C-MET PET were evaluated. Regarding the management impact, the rate of scans that caused changes in intended management was also evaluated. Moreover, the occurrence of scans having detrimental diagnostic impact (DDI) and beneficial diagnostic impact (BDI) were evaluated. RESULTS: Sensitivity, specificity, and accuracy of (11)C-MET PET was 87.8, 80.0, and 85.9%. The intended management was changed in 50.0% of the scans. DDI and BDI were observed in 4.3 and 36.2% of the total relevant scans, respectively. CONCLUSION: (11)C-MET PET can provide useful information in initial diagnosis and differentiating tumor recurrence from radiation necrosis. The intended management was changed in half of the scans. Since a few cases did not receive the requisite treatment due to false-negative results of (11)C-MET PET, management decision should be made carefully, especially in the case of a negative scan.

Low-dose non-enhanced CT versus full-dose contrast-enhanced CT in integrated PET/CT studies for the diagnosis of uterine cancer recurrence.

PURPOSE: To evaluate low-dose non-enhanced CT (ldCT) and full-dose contrast-enhanced CT (ceCT) in integrated (18)F-fluorodeoxyglucose (FDG) PET/CT studies for restaging of uterine cancer. METHODS: A group of 100 women who had undergone treatment for uterine cervical (n=55) or endometrial cancer (n=45) underwent a conventional PET/CT scans with ldCT, and then a ceCT scan. Two observers retrospectively reviewed and interpreted the PET/ldCT and PET/ceCT images in consensus using a three-point grading scale (negative, equivocal, or positive) per patient and per lesion. Final diagnoses were obtained by histopathological examination, or clinical follow-up for at least 6 months. RESULTS: Patient-based analysis showed that the sensitivity, specificity and accuracy of PET/ceCT were 90% (27/30), 97% (68/70) and 95% (95/100), respectively, whereas those of PET/ldCT were 83% (25/30), 94% (66/70) and 91% (91/100), respectively. Sensitivity, specificity and accuracy did not significantly differ between two methods (McNemar test, p=0.48, p=0.48, and p=0.13, respectively). There were 52 sites of lesion recurrence: 12 pelvic lymph node (LN), 11 local recurrence, 8 peritoneum, 7 abdominal LN, 5 lung, 3 supraclavicular LN, 3 liver, 2 mediastinal LN, and 1 muscle and bone. The grading results for the 52 sites of recurrence were: negative 5, equivocal 0 and positive 47 for PET/ceCT, and negative 5, equivocal 4 and positive 43 for PET/ldCT, respectively. Four equivocal regions by PET/ldCT (local recurrence, pelvic LN metastasis, liver metastasis and muscle metastasis) were correctly interpreted as positive by PET/ceCT. CONCLUSION: PET/ceCT is an accurate imaging modality for the assessment of uterine cancer recurrence. Its use reduces the frequency of equivocal interpretations.

Evaluation of PiB visual interpretation with CSF Aß and longitudinal SUVR in J-ADNI study.

OBJECTIVE: The objectives of the present study were to investigate (1) whether trinary visual interpretation of amyloid positron emission tomography (PET) imaging (negative/equivocal/positive) reflects quantitative amyloid measurements and the time course of 11C-Pittsburgh compound B (PiB) amyloid accumulation, and (2) whether visually equivocal scans represent an early stage of the Alzheimer's disease (AD) continuum in terms of an intermediate state of quantitative amyloid measurements and the changes in amyloid accumulation over time. METHODS: From the National Bioscience Database Center Human Database of the Japanese Alzheimer's Disease Neuroimaging Initiative, we selected 133 individuals for this study including 33 with Alzheimer's disease dementia (ADD), 52 with late mild cognitive impairment (LMCI), and 48 cognitively normal (CN) subjects who underwent clinical assessment, PiB PET, and structural magnetic resonance imaging (MRI) with 2 or 3-years of follow-up. Sixty-eight of the 133 individuals underwent cerebrospinal fluid amyloid-ß1-42 (CSF-Ab42) analysis at baseline. The standard uptake value ratio (SUVR) of PiB PET was calculated with a method using MRI at each visit. The cross-sectional values, longitudinal changes in SUVR, and baseline CSF-Ab42 were compared among groups, which were categorized based on trinary visual reads of amyloid PET (negative/equivocal/positive). RESULTS: From the trinary visual interpretation of the PiB PET images, 55 subjects were negative, 8 were equivocal, and 70 were positive. Negative interpretation was most frequent in the CN group (70.8/10.4/18.8%: negative/equivocal/positive), and positive was most frequent in the LMCI group (34.6/1.9/63.5%) and in the ADD group (9.1/6.1/84.8%). The baseline SUVRs were 1.08 ± 0.06 in the negative group, 1.23 ± 0.15 in the equivocal group, and 1.86 ± 0.31 in the positive group (F = 174.9, p < 0.001). The baseline CSF-Ab42 level was 463 ± 112 pg/mL in the negative group, 383 ± 125 pg/mL in the equivocal group, and 264 ± 69 pg/mL in the positive group (F = 37, p < 0.001). Over the 3-year follow-up, annual changes in SUVR were - 0.00 ± 0.02 in the negative group, 0.02 ± 0.02 in the equivocal group, and 0.04 ± 0.07 in the positive group (F = 8.4, p < 0.001). CONCLUSIONS: Trinary visual interpretation (negative/equivocal/positive) of amyloid PET imaging reflects quantitative amyloid measurements evaluated with PET and the CSF amyloid test as well as the amyloid accumulation over time evaluated with PET over 3 years. Subjects in the early stage of the AD continuum could be identified with an equivocal scan, because they showed intermediate quantitative amyloid PET, CSF measurements, and the amyloid accumulation over time.