[en] In order to study the production mechanism of projectile-like fragments (PLFs) at intermediate energies, the momentum distributions of PLFs were measured. For this purpose, the momentum distributions of PLFs were measured by using a secondary beam course. Longitudinal and transverse momentum (P_L and P_T) distributions of PLFs produced in the reaction with ⁸⁴Kr beam at E/A=290 MeV were observed. The deflection effect caused by Coulomb force was provided through the analysis of P_T distribution by using off-centered Gaussian Functions. (author)

[en] 

Objective

Patients often take prescription drugs for various diseases or complications that contain several grams of glucose. However, the effect of these glucose-containing medications on the image quality of F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has not been established. This study aimed to evaluate the effect of taking drugs containing glucose before an FDG-PET on the PET image quality.

Methods

In total, 736 continuously enrolled patients who underwent FDG-PET were retrospectively analysed. We investigated the total glucose content in the prescription drugs that each patient took during fasting before the FDG injection, and we divided the patients into three groups according to the amount of glucose in their drugs: group A did not take any drugs containing glucose, group B took sugar-coated tablets (containing trace amounts of glucose), and group C took prescription drugs with glucose an ingredient. Visual scores and quantitative variables with standard uptake value (SUV) for the brain, myocardium, blood, liver, and muscle in the FDG-PET images were analysed and statistically compared across the three groups.

Results

In group C, the amount of glucose was 0.63 ± 0.86 g (maximum 4.9 g). For the visual scores, there were no significant differences among the three groups. For the quantitative variables, significant differences were present in the brain SUVmax, muscle SUVmean, brain/blood ratio, brain/liver ratio, and brain/muscle ratio. However, a multivariate analysis showed that the group indicator was not significantly associated with any of the quantitative variables. On the other hand, blood glucose was significantly associated with the visual and quantitative variables. In group C, the correlation coefficient between the amount of glucose and the blood glucose level, the visual scores and the quantitative variables were in the range of − 0.121 to 0.100 and were not significant.

Conclusions

There were no significant differences between glucose-containing medications before FDG-PET and the visual scores and quantitative variables for FDG-PET image. Several grams of glucose in drugs before FDG-PET can be ignored.

[en] Nuclear medicine is a technique that can be used for both diagnosis and treatment. FDG PET is a widely used technique as an in-vivo image of cancer, but its physiological accumulation in normal brain tissue is problematic especially for brain tumor imaging. ¹¹C- methionine overcomes this disadvantage, but has different drawbacks such as a short half-life. Although nuclear medicine therapy for brain tumors is still in the clinical trial stage, several radiopharmaceuticals, including beta and alpha emitters, are expected to be used for the treatment of brain tumors in the future. (author)

[en] Currently, there are multiple active clinical trials involving poly(ADP-ribose) polymerase (PARP) inhibitors in the treatment of glioblastoma. The noninvasive quantification of baseline PARP expression using positron emission tomography (PET) may provide prognostic information and lead to more precise treatment. Due to the lack of brain-penetrant PARP imaging agents, the reliable and accurate in vivo quantification of PARP in the brain remains elusive. Herein, we report the synthesis of a brain-penetrant PARP PET tracer, (R)-2-(2-methyl-1-(methyl-${}^{11}$C)pyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide ([${}^{11}$C]PyBic), and its preclinical evaluations in a syngeneic RG2 rat glioblastoma model and healthy nonhuman primates. We synthesized [${}^{11}$C]PyBic using veliparib as the labeling precursor, performed dynamic PET scans on RG2 tumor-bearing rats and calculated the distribution volume ratio (DVR) using simplified reference region method 2 (SRTM2) with the contralateral nontumor brain region as the reference region. We performed biodistribution studies, western blot, and immunostaining studies to validate the in vivo PET quantification results. We characterized the brain kinetics and binding specificity of [${}^{11}$C]PyBic in nonhuman primates on FOCUS220 scanner and calculated the volume of distribution (V${}_T$), nondisplaceable volume of distribution (V${}_{ND}$), and nondisplaceable binding potential (BP${}_{ND}$) in selected brain regions. [${}^{11}$C]PyBic was synthesized efficiently in one step, with greater than 97% radiochemical and chemical purity and molar activity of 148 ± 85 MBq/nmol (n = 6). [${}^{11}$C]PyBic demonstrated PARP-specific binding in RG2 tumors, with 74% of tracer binding in tumors blocked by preinjected veliparib (i.v., 5 mg/kg). The in vivo PET imaging results were corroborated by ex vivo biodistribution, PARP1 immunohistochemistry and immunoblotting data. Furthermore, brain penetration of [${}^{11}$C]PyBic was confirmed by quantitative monkey brain PET, which showed high specific uptake (BP${}_{ND}$ > 3) and low nonspecific uptake (V${}_{ND}$< 3 mL/cm${}^3$) in the monkey brain. [${}^{11}$C]PyBic is the first brain-penetrant PARP PET tracer validated in a rat glioblastoma model and healthy nonhuman primates. The brain kinetics of [${}^{11}$C]PyBic are suitable for noninvasive quantification of available PARP binding in the brain, which posits [${}^{11}$C]PyBic to have broad applications in oncology and neuroimaging.

[en] PET has the potential to perform absolute in vivo radiotracer quantitation. This potential can be compromised by voluntary body motion (BM), which degrades image resolution, alters apparent tracer uptakes, introduces CT-based attenuation correction mismatch artifacts and causes inaccurate parameter estimates in dynamic studies. Existing body motion correction (BMC) methods include frame-based image-registration (FIR) approaches and real-time motion tracking using external measurement devices. FIR does not correct for motion occurring within a pre-defined frame and the device-based method is generally not practical in routine clinical use, since it requires attaching a tracking device to the patient and additional device set up time. In this paper, we proposed a data-driven algorithm, centroid of distribution (COD), to detect BM. In this algorithm, the central coordinate of the time-of-flight (TOF) bin, which can be used as a reasonable surrogate for the annihilation point, is calculated for every event, and averaged over a certain time interval to generate a COD trace. We hypothesized that abrupt changes on the COD trace in lateral direction represent BMs. After detection, BM is estimated using non-rigid image registrations and corrected through list-mode reconstruction. The COD-based BMC approach was validated using a monkey study and was evaluated against FIR using four human and one dog studies with multiple tracers. The proposed approach successfully detected BMs and yielded superior correction results over conventional FIR approaches. (paper)

[en] Tumor necrosis is one of the indicators of tumor aggressiveness. "1"8F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor. (orig.)

[en] Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV x FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients. (orig.)

[en] Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a benign lymphoid proliferation or malignant lymphoma in patients who have been treated with MTX. MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Here we evaluated the diagnostic accuracy and predictive value of "1"8F-fluorodeoxyglucose positron emission tomography/computed tomography ("1"8F-FDG PET/CT) for MTX-LPD. We retrospectively investigated the cases of 15 patients clinically suspected of having MTX-LPD. A total of 324 anatomic regions (207 nodal and 117 extranodal regions) were assessed by "1"8F-FDG PET/CT and by multi-detector row CT (MDCT). Each anatomic region was classified as either malignant or benign. The uptake of "1"8F-FDG was assessed semi-quantitatively with the standardized uptake value maximum (SUVmax), the whole-body metabolic tumor volume (WBMTV), and the whole-body total lesion glycolysis (WBTLG) in order to investigate predictive factors of spontaneous regression after the withdrawal of MTX. MTX-LPD lesions were observed in 92/324 (28.4 %) regions. "1"8F-FDG PET/CT showed 90.2 % sensitivity, 97.4 % specificity, and 95.4 % accuracy, values which were significantly higher than those of MDCT (59.8, 94.8, and 84.9 %, respectively. p < 0.002). After the withdrawal of MTX, 9/15 patients (60.0 %) achieved complete response (CR). The SUVmax, WBMTV and WBTLG values of the CR patients were 9.2 (range 2.8–47.1), 44.3 (range 0–362.6) ml, 181.8 (range 0–2180.9) ml, respectively, which were not significantly different from those of the non-CR patients: 10.6 (range 0–24.9), 15.7 (range 0–250.1) ml, and 97.4 (range 0–1052.1) ml. Although "1"8F-FDG PET/CT was a useful tool to detect MTX-LPD lesions, none of the "1"8F-FDG PET parameters before the withdrawal of MTX could be used to predict CR after the withdrawal of MTX

[en] A novel deep learning (DL)-based attenuation correction (AC) framework was applied to clinical whole-body oncology studies using ${}^{18}$F-FDG, ${}^{68}$Ga-DOTATATE, and ${}^{18}$F-Fluciclovine. The framework used activity (λ-MLAA) and attenuation (µ-MLAA) maps estimated by the maximum likelihood reconstruction of activity and attenuation (MLAA) algorithm as inputs to a modified U-net neural network with a novel imaging physics-based loss function to learn a CT-derived attenuation map (µ-CT). Clinical whole-body PET/CT datasets of ${}^{18}$F-FDG (N = 113), ${}^{68}$Ga-DOTATATE (N = 76), and ${}^{18}$F-Fluciclovine (N = 90) were used to train and test tracer-specific neural networks. For each tracer, forty subjects were used to train the neural network to predict attenuation maps (µ-DL). µ-DL and µ-MLAA were compared to the gold-standard µ-CT. PET images reconstructed using the OSEM algorithm with µ-DL (OSEM${}_{DL}$) and µ-MLAA (OSEM${}_{MLAA}$) were compared to the CT-based reconstruction (OSEM${}_{CT}$). Tumor regions of interest were segmented by two radiologists and tumor SUV and volume measures were reported, as well as evaluation using conventional image analysis metrics. µ-DL yielded high resolution and fine detail recovery of the attenuation map, which was superior in quality as compared to µ-MLAA in all metrics for all tracers. Using OSEM${}_{CT}$ as the gold-standard, OSEM${}_{DL}$ provided more accurate tumor quantification than OSEM${}_{MLAA}$ for all three tracers, e.g., error in SUV${}_{max}$ for OSEM${}_{MLAA}$ vs. OSEM${}_{DL}$: - 3.6 ± 4.4% vs. - 1.7 ± 4.5% for ${}^{18}$F-FDG (N = 152), - 4.3 ± 5.1% vs. 0.4 ± 2.8% for ${}^{68}$Ga-DOTATATE (N = 70), and - 7.3 ± 2.9% vs. - 2.8 ± 2.3% for ${}^{18}$F-Fluciclovine (N = 44). OSEM${}_{DL}$ also yielded more accurate tumor volume measures than OSEM${}_{MLAA}$, i.e., - 8.4 ± 14.5% (OSEM${}_{MLAA}$) vs. - 3.0 ± 15.0% for ${}^{18}$F-FDG, - 14.1 ± 19.7% vs. 1.8 ± 11.6% for ${}^{68}$Ga-DOTATATE, and - 15.9 ± 9.1% vs. - 6.4 ± 6.4% for ${}^{18}$F-Fluciclovine. The proposed framework provides accurate and robust attenuation correction for whole-body ${}^{18}$F-FDG, ${}^{68}$Ga-DOTATATE and ${}^{18}$F-Fluciclovine in tumor SUV measures as well as tumor volume estimation. The proposed method provides clinically equivalent quality as compared to CT in attenuation correction for the three tracers.

[en] Exploring synaptic density changes during brain growth is crucial to understanding brain development. Previous studies in nonhuman primates report a rapid increase in synapse number between the late gestational period and the early neonatal period, such that synaptic density approaches adult levels by birth. Prenatal synaptic development may have an enduring impact on postnatal brain development, but precisely how synaptic density changes in utero are unknown because current methods to quantify synaptic density are invasive and require post-mortem brain tissue. We used synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) radioligands [${}^{11}$C]UCB-J and [${}^{18}$F]Syn-VesT-1 to conduct the first assessment of synaptic density in the developing fetal brain in gravid rhesus monkeys. Eight pregnant monkeys were scanned twice during the third trimester at two imaging sites. Fetal post-mortem samples were collected near term in a subset of subjects to quantify SV2A density by Western blot. Image-derived fetal brain SV2A measures increased during the third trimester. SV2A concentrations were greater in subcortical regions than in cortical regions at both gestational ages. Near term, SV2A density was higher in primary motor and visual areas than respective associative regions. Post-mortem quantification of SV2A density was significantly correlated with regional SV2A PET measures. While further study is needed to determine the exact relationship of SV2A and synaptic density, the imaging paradigm developed in the current study allows for the effective in vivo study of SV2A development in the fetal brain.