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PurposeGlycolysis is increased by hypoxia, suggesting a possible correlation between the accumulation of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in malignant tumors and regional hypoxia defined by 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole (FMISO) PET. The aim of this study is to investigate the intra-tumoral spatial distribution and quantitative relationship between FDG and FMISO in a cohort of head and neck squamous cell cancer (HNSCC) patients.MethodsTwenty HNSCC patients with 20 primary tumors and 19 metastatic lymph nodes (LNs) underwent FDG and FMISO PET within 1 week. The metabolic target volume (MTV) was defined on the FDG PET images using a region growing algorithm. The hypoxic volume (HV) was defined by the volume of voxels in an FMISO image within the MTV that satisfy a tumor-to-blood ratio (T/B) greater than 1.2. FDG and FMISO lesions were co-registered, and a voxel-by-voxel correlation between the two datasets was performed. FDG and FMISO TVs’ SUVs were also compared as well as the intra-tumoral homogeneity of the two radiotracers. Separate analysis was performed for the primary tumors and LNs.ResultsTwenty-six percent of the primary tumors and 15% of LNs showed a strong correlation (R > 0.7) between FDG and FMISO intra-tumor distributions when considering the MTV. For the HV, only 19% of primary tumors and 12% of LN were strongly correlated. A weak and moderate correlation existed between the two markers SUVavg, and SUVmax in the case of the primary tumors, respectively. However, this was not the case for the LNs. Good concordances were also observed between the primary tumor’s and LNs HV SUVavgs as well as between the corresponding hypoxic fractions (HF’s).ConclusionsA moderate correlation between FDG and hypoxia radiotracer distribution, as measured by FMISO, seems to exist for primary tumors. However, discordant results were found in the case of LNs. Hypoxia appears to be the dominant driver of high FDG uptake in selected tumors only, and therefore FDG PET images cannot be used as a universal surrogate to identify or predict intra-tumor hypoxia.

Changes in cardiac metabolism typically precede cardiac dysfunction and therefore represent an important target for diagnosis and treatment designed to prevent progression to heart failure, a leading cause of death. Profound changes in pyruvate metabolism, including reduced expression of the mitochondrial pyruvate carrier (MPC), are increasingly recognized as early maladaptive alterations in cardiomyopathies, but no methods currently exist to determine MPC expression in vivo. We exposed mice to doxorubicin (DOX), an anthracycline chemotherapeutic known to perturb pyruvate metabolism, and demonstrated that cardiac tissue levels of MPC decrease within 4 weeks of initial DOX exposure. Using a combination of stable isotope tracing metabolomics, hyperpolarized [1- 13 C]pyruvate magnetic resonance imaging (MRI), and [3- 11 C]pyruvate positron emission tomography (PET), we found that loss of MPC and monocarboxylate transporter 1 (MCT1) resulted in decreased utilization of pyruvate for mitochondrial oxidative metabolism and resulted in decreased cardiac carbon-11 clearance. Despite recovery of expression levels of pyruvate transporters, including MPC, 16 weeks after initial DOX exposure, cardiac carbon-11 clearance still trends towards differences between control mice and the mice exposed to this chemotherapeutic. [3- 11 C]Pyruvate PET is therefore a promising approach to imaging cardiac pyruvate transport with potential applications to the identification of early maladaptive changes in pyruvate metabolism and monitoring response to therapy.

Background [ 18 F]MK-6240 is a neurofibrillary tangles PET radiotracer that has been broadly used in aging and Alzheimer’s disease (AD) studies. Majority of [ 18 F]MK-6240 PET studies use dynamic acquisitions longer than 60 min to assess the tracer kinetic parameters. As of today, no consensus has been established on the optimum dynamic PET scan time. In this study, we assess the reproducibility of [ 18 F]MK-6240 quantitative metrics using shortest dynamic PET protocols in cognitively normal subjects. PET metrics were measured through two-tissue compartment model (2TCM) and Logan model to estimate VT and DVR, as well as SUVR from 90 to 120 min (SUVR 90 − 120 min ) post-tracer injection for brain regions. 2TCM was carried out using the 120 min dynamic coffee break dataset (first scan from 0 to 60 min p.i., second scan from 90 to 120 min p.i.) and then repeated after stepwise shortening it by 5 min. The dynamic scan length that reproduced the 120 min dynamic scans-based VT to within 10% error was defined as the shortest acquisition time (SAT). The SAT SUVR 90 − 120 min was deduced from the SAT dataset by extrapolation of each image pixel time-activity curve to 120 min. The reproducibility of the 120 min dynamic scans-based VT 2TCM , DVR 2TCM , DVR Logan , and SUVR using the SAT was assessed using Passing-Bablock analysis. The limits of reproducibility of each PET metrics were determined using Bland-Altman analysis. Results A dynamic SAT of 40 min yielded < 10% error in [ 18 F]MK-6240 VT 2TCM ’s for all brain regions, compared to those measured using the 120 min datasets. SAT-based analysis did not show statistically significant systemic or proportional biases in VT 2TCM , DVR 2TCM , DVR Logan , or SUVR compared to those deduced from the full dynamic dataset of 120 min. A mean difference between the 120 min- and SAT-based analysis of less than 4%, 10%, 15%, and 20% existed in the VT 2TCM , DVR 2TCM , DVR Logan , and SUVR respectively. Conclusion Kinetic modeling of [ 18 F]MK-6240 PET can be accurately performed using dynamic scan times as short as 40 min. This can facilitate studies with [ 18 F]MK-6240 PET and improve patients accrual. Further work would be necessary to confirm the reproducibility of these results for patients in dementia spectra.

Objectives: This study aims to assess the value of FLT-PET as a non-invasive tool to differentiate between patients with ET and Pre-PMF. This study is a pilot study to have a proof of concept only. Methods: This is a prospective, interventional study where a total of 12 patients were included. Each patient underwent FLT PET imaging as well as bone marrow examination (gold standard). In addition, semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen, and Lspine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <.05 is considered to be statistically significant. Results: The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P > .05). In contrast, TLG measurements in the LSpine were statistically different (P = .013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion: This study is a proof of concept about the potential to discriminate between ET and pre-PMF patients in a non-invasive way. TLG of the LSpine in FLT PET images is a potential quantitative parameter to distinguish between ET and pre-PMF patients.

IntroductionQuantitative positron emission tomography (PET) studies of neurodegenerative diseases typically require the measurement of arterial input functions (AIF), an invasive and risky procedure. This study aims to assess the reproducibility of [11C]DPA-713 PET kinetic analysis using population-based input function (PBIF). The final goal is to possibly eliminate the need for AIF.Materials and methodsEighteen subjects including six healthy volunteers (HV) and twelve Parkinson disease (PD) subjects from two [11C]-DPA-713 PET studies were included. Each subject underwent 90 min of dynamic PET imaging. Five healthy volunteers underwent a test-retest scan within the same day to assess the repeatability of the kinetic parameters. Kinetic modeling was carried out using the Logan total volume of distribution (VT) model. For each data set, kinetic analysis was performed using a patient-specific AIF (PSAIF, ground-truth standard) and then repeated using the PBIF. PBIF was generated using the leave-one-out method for each subject from the remaining 17 subjects and after normalizing the PSAIFs by 3 techniques: (a) Weightsubject×DoseInjected, (b) area under AIF curve (AUC), and (c) Weightsubject×AUC. The variability in the VT measured with PSAIF, in the test-retest study, was determined for selected brain regions (white matter, cerebellum, thalamus, caudate, putamen, pallidum, brainstem, hippocampus, and amygdala) using the Bland-Altman analysis and for each of the 3 normalization techniques. Similarly, for all subjects, the variabilities due to the use of PBIF were assessed.ResultsBland-Altman analysis showed systematic bias between test and retest studies. The corresponding mean bias and 95% limits of agreement (LOA) for the studied brain regions were 30% and ± 70%.Comparing PBIF- and PSAIF-based VT estimate for all subjects and all brain regions, a significant difference between the results generated by the three normalization techniques existed for all brain structures except for the brainstem (P-value = 0.095). The mean % difference and 95% LOA is −10% and ±45% for Weightsubject×DoseInjected; +8% and ±50% for AUC; and +2% and ± 38% for Weightsubject×AUC. In all cases, normalizing by Weightsubject×AUC yielded the smallest % bias and variability (% bias = ±2%; LOA = ±38% for all brain regions).Estimating the reproducibility of PBIF-kinetics to PSAIF based on disease groups (HV/PD) and genotype (MAB/HAB), the average VT values for all regions obtained from PBIF is insignificantly higher than PSAIF (%difference = 4.53%, P-value = 0.73 for HAB; and %difference = 0.73%, P-value = 0.96 for MAB). PBIF also tends to overestimate the difference between PD and HV for HAB (% difference = 32.33% versus 13.28%) and underestimate it in MAB (%difference = 6.84% versus 20.92%).ConclusionsPSAIF kinetic results are reproducible with PBIF, with variability in VT within that obtained for the test-retest studies. Therefore, VT assessed using PBIF-based kinetic modeling is clinically feasible and can be an alternative to PSAIF.

PurposeTotal body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative.MethodsSeveral medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows.ConclusionsA medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options.

Background Hypoxic tumours exhibit increased resistance to radiation, chemical, and immune therapies. 18 F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a non-invasive, quantitative imaging technique used to evaluate the presence and spatial distribution of tumour hypoxia. To facilitate the use of FMISO PET for identification of individuals likely to benefit from hypoxia-targeted treatments, we investigated the reproducibility of FMISO PET spatiotemporal intratumour distribution in patients with non-small cell lung cancer (NSCLC). Methods Ten patients underwent 18 F-fluorodeoxyglucose (FDG) PET/CT scans, followed by two FMISO PET/CT scans 1–2 days apart. Nineteen lesions in total were segmented from co-registered FDG PET image sets. Volumes of interest were also defined on normal contralateral lung and subscapularis muscle. The Pearson correlation coefficient r was calculated for mean standardized uptake values (SUV) within investigated volumes of interest and for voxels within tumour volumes ( r TV ). The reproducibility of FMISO voxelwise distribution, SUV- and tumour-to-blood ratio (TBR)-derived indices was assessed using correlation and Bland-Altman analyses. Results The SUV max , SUV mean , TBR max , and TBR mean were highly correlated ( r  ≥ 0.87, p  < 0.001) and were reproducible to within 10–15 %. The mean r TV was 0.84 ± 0.10. 77 % of voxels identified as hypoxic on one FMISO scan were confirmed as such on the other FMISO scan. Mean voxelwise differences between TBR values as calculated from pooled data including all lesions were 0.9 ± 10.8 %. Conclusions High reproducibility of FMISO intratumour distribution in NSCLC patients was observed, facilitating its use in determining the topology of the hypoxic tumour sub-volumes for dose escalation, in patient stratification strategies for hypoxia-targeted therapies, and in monitoring response to therapeutic interventions. Trial registration Current Controlled Trials NCT02016872

Attenuation correction (AC) of PET images with helical CT (HCT) in PET/CT matches only the spatial resolution of CT and PET, not the temporal resolution. We therefore proposed the use of respiration-averaged CT (ACT) to match the temporal resolution of CT and PET and evaluated the improvement of tumor quantification in PET images of the thorax with ACT. First, we examined 100 consecutive clinical PET/CT studies for the frequency and magnitude of misalignment at the diaphragm position between the HCT and the PET data. Patients were injected with 555-740 MBq of (18)F-FDG and scanned 1 h after injection. The HCT data were acquired at the following settings: 120 kV, 300 mA, pitch of 1.35:1, collimation of 8 x 1.25 mm, and rotation cycle of 0.5 s. Patients were instructed to hold their breath at midexpiration during HCT of the thorax. The PET acquisition was 3 min per bed. Second, we retrospectively analyzed studies of 8 patients (1 with esophageal cancer and 7 with lung cancer). Each study included regular PET/CT followed by 4-dimensional (4D) CT for radiation treatment planning. We compared the results of AC of the PET data with HCT and ACT. There were 13 tumors in these 8 patients. The 4D CT data were acquired at the following settings: 120 kV, 50-150 mA, cine duration of 1 breathing cycle plus 1 s, collimation of 8 x 1.25 mm, and rotation cycle of 0.5 s. The acquisition was taken when the patient was in the free-breathing state. We averaged the 10 phases of the 4D CT data to obtain ACT for AC of the PET data. Both the ACT and the HCT data were used for AC of the same PET data. There was a misalignment between the HCT and the PET data in 50 of 100 patient studies. In 34 studies, the misalignment was greater than 2 cm. In a comparison of HCT and ACT, 5 tumors had differences in standardized uptake values (SUV) between HCT-and ACT-attenuation-corrected PET of less than 20%, and 4 tumors had differences in SUV of more than 50%. The latter 4 tumors were found in the patient with esophageal cancer and in 2 of the patients with lung cancer. The PET data from these 3 patients had a misalignment of 2-4.5 cm relative to the HCT data. Breathing artifacts were significantly reduced by ACT. Seven of the 8 patients had a lower diaphragm position on HCT than on ACT, suggesting that the patients tended to hold a deeper breath during HCT than during ACT. The high rate of misalignment suggested a potential mismatch between the HCT and the PET data with the limited-breath-hold CT protocol. In the comparison of HCT and ACT, significant differences (>50%) in SUV were attributable to different breathing states between HCT and PET. The PET data corrected by ACT did not show breathing artifacts, suggesting that ACT may be more accurate than HCT for AC of the PET data.

The goal of this study was to describe our initial experience with the deep-inspiration breath-hold (DIBH) technique in combined PET/CT of the thorax. This article presents particular emphasis on the technical aspects required for clinical implementation. In the DIBH technique, the patient is verbally coached and brought to a reproducible deep inspiration breath-hold level. The first \"Hold\" period, which refers to the CT session, is considered as the reference. This is followed by 9- to 20-s independent breath-hold PET acquisitions. The goal is to correct for respiratory motion artifacts and, consequently, improve the tumor quantitation and localization on the PET/CT images and inflate the lungs for possible improvement in the detection of subcentimeter pulmonary nodules. A physicist monitors and records patient breathing during PET/CT acquisition using a motion tracker. Patient breathing traces obtained during acquisition are examined on the fly to assess the reproducibility of the technique. Data from 8 patients, encompassing 10 lesions, were analyzed. Visual inspection of fused PET/CT images showed improved spatial matching between the 2 modalities, reduced motion artifacts especially in the diaphragm, and increased the measured standardized uptake value (SUV) attributed to reduced motion blurring, as compared with the standard clinical PET/CT images. The practice of DIBH PET/CT is feasible in a clinical setting. With this technique, consistent lung inflation levels are achieved during PET/CT sessions, as judged by both motion tracker and verification of spatial matching between PET and CT images. Breathing-induced motion artifacts are significantly reduced using DIBH compared with free breathing, enabling better target localization and quantitation. The DIBH technique showed an increase in the median SUV by 32.46%, with a range from 4% to 83%, compared with SUVs measured on the clinical images. The median percentage reduction in the PET-to-CT lesions' centroids was 26.6% (range, 3%-50%).

We have developed a new technique to gate lung 18F-FDG PET images in synchronization with the respiratory motion to reduce smearing due to breathing and improve quantitation of 18F-FDG uptake in lung lesions. A camera-based respiratory gating system, the real-time position management (RPM), is used to monitor the respiratory cycle. The RPM provides a trigger to the PET scanner to initiate the gating cycle. Each respiratory cycle is divided into discrete bins triggered at a defined amplitude or phase within the patient's breathing motion, into which PET data are acquired. The acquired data within the time bins correspond to different lesion positions within the breathing cycle. The study includes 5 patients with lung cancer. Measurements of the lesions' volumes in the gated mode showed a reduction of up to 34% compared with that of the nongated measurement. This reduction in the lesion volume has been accompanied by an increase in the intensity in the 18F-FDG signal per voxel. This finding has resulted in an improvement in measurement of the maximum standardized uptake value (SUV(max)), which increased in 1 patient by as much as 159%. The total lesion glycolysis, defined as the product of the SUV(max) and the lesion volume, was also measured in gated and nongated modes and showed a consistency between the 2 measurements. We have shown that image smearing can be reduced by gating 18F-FDG PET images in synchronization with the respiratory motion. This technique allows a more accurate definition of the lesion volume and improves the quantitation specific activity of the tracer (in this case, 18F-FDG), which are distorted because of the breathing motion.