PET Uptake Research Articles

Deep learning for Dixon MRI-based attenuation correction in PET/MRI of head and neck cancer patients

BackgroundQuantitative whole-body PET/MRI relies on accurate patient-specific MRI-based attenuation correction (AC) of PET, which is a non-trivial challenge, especially for the anatomically complex head and neck region. We used a deep learning model developed for dose planning in radiation oncology to derive MRI-based attenuation maps of head and neck cancer patients and evaluated its performance on PET AC.MethodsEleven head and neck cancer patients, referred for radiotherapy, underwent CT followed by PET/MRI with acquisition of Dixon MRI. Both scans were performed in radiotherapy position. PET AC was performed with three different patient-specific attenuation maps derived from: (1) Dixon MRI using a deep learning network (PETDeep). (2) Dixon MRI using the vendor-provided atlas-based method (PETAtlas). (3) CT, serving as reference (PETCT). We analyzed the effect of the MRI-based AC methods on PET quantification by assessing the average voxelwise error within the entire body, and the error as a function of distance to bone/air. The error in mean uptake within anatomical regions of interest and the tumor was also assessed.ResultsThe average (± standard deviation) PET voxel error was 0.0 ± 11.4% for PETDeep and −1.3 ± 21.8% for PETAtlas. The error in mean PET uptake in bone/air was much lower for PETDeep (−4%/12%) than for PETAtlas (−15%/84%) and PETDeep also demonstrated a more rapidly decreasing error with distance to bone/air affecting only the immediate surroundings (less than 1 cm). The regions with the largest error in mean uptake were those containing bone (mandible) and air (larynx) for both methods, and the error in tumor mean uptake was −0.6 ± 2.0% for PETDeep and −3.5 ± 4.6% for PETAtlas.ConclusionThe deep learning network for deriving MRI-based attenuation maps of head and neck cancer patients demonstrated accurate AC and exceeded the performance of the vendor-provided atlas-based method both overall, on a lesion-level, and in vicinity of challenging regions such as bone and air.

Correlation of Intraoperative 5-ALA-Induced Fluorescence Intensity and Preoperative 11C-Methionine PET Uptake in Glioma Surgery.

Simple SummaryIn malignant brain tumor surgery, precise identification of the tumor is essential. 5-Aminolevulinic acid (5-ALA) labels tumor cells with red fluorescence to facilitate tumor resection. On the other hand, the nuclear medicine imaging technique, positron emission tomography with 11C-methionine (MET-PET), can delineate tumors precisely but is not widely available. This study aimed to determine the correlation between intraoperative 5-ALA-induced fluorescence and preoperative MET-PET signals of gliomas. We quantitatively measured the fluorescence intensity from tumor samples and calculated the MET-PET uptake by the tumor. Our study showed that strong tumor fluorescence correlated with high MET-PET uptake and cellular proliferation. Our findings might be valuable to rapidly provide information on tumor biology at the time of surgery in circumstances where MET-PET is inaccessible.Background: 5-Aminolevulinic acid (5-ALA) is widely employed to assist fluorescence-guided surgery for malignant brain tumors. Positron emission tomography with 11C-methionine (MET-PET) represents the activity of brain tumors with precise boundaries but is not readily available. We hypothesized that quantitative 5-ALA-induced fluorescence intensity might correlate with MET-PET uptake in gliomas. Methods: Adult patients with supratentorial astrocytic gliomas who underwent preoperative MET-PET and surgical tumor resection using 5-ALA were enrolled in this prospective study. The regional tumor uptake of MET-PET was expressed as the ratio of standardized uptake volume max to that of the normal contralateral frontal lobe. A spectrometric fluorescence detection system measured tumor specimens’ ex vivo fluorescence intensity at 635 nm. Ki-67 index and IDH mutation status were assessed by histopathological analysis. Use of an antiepileptic drug (AED) and contrast enhancement pattern on MRI were also investigated. Results: Thirty-two patients, mostly with Glioblastoma IDH wild type (46.9%) and anaplastic astrocytoma IDH mutant (21.9%), were analyzed. When the fluorescence intensity was ranked into four groups, the strongest fluorescence group exhibited the highest mean MET-PET uptake and Ki-67 index values. When rearranged into fluorescence Visible or Non-visible groups, the Visible group had significantly higher MET-PET uptake and Ki-67 index compared to the Non-visible group. Contrast enhancement on MRI and IDH wild type tumors were more frequent among the Visible group. AED use did not correlate with 5-ALA-induced fluorescence intensity. Conclusions: In astrocytic glioma surgery, visible 5-ALA-induced fluorescence correlated with high MET-PET uptake, along with a high Ki-67 index.

Technical note: A PET/MR coil with an integrated, orbiting 511keV transmission source for PET/MR imaging validated in an animal study.

BackgroundMR‐based methods for attenuation correction (AC) in PET/MRI either neglect attenuation of bone, or use MR‐signal derived information about bone, which leads to a bias in quantification of tracer uptake in PET. In a previous study, we presented a PET/MRI specific MR coil with an integrated transmission source (TX) system allowing for direct measurement of attenuation. In phantom measurements, this system successfully reproduced the linear attenuation coefficient of water.PurposeThe purpose of this study is to validate the TX system in a clinical setting using animals and to show its applicability compared to standard clinical methods.MethodsAs test subject, a 15‐kg piglet was injected with 53 MBq of 18F‐NaF. The μ‐map obtained with the TX system and the reconstructed activity distribution were compared to four established AC methods: a Dixon sequence, an ultra‐short echo time (UTE) sequence, a CT scan, and a 511 keV transmission scan using a Siemens ECAT EXACT HR+ as the reference. The PET/MRI measurements were performed on a Siemens Biograph mMR to obtain the μ‐map using the TX system as well as the Dixon and UTE sequence directly followed by the CT and ECAT measurements.ResultsThe reconstructed activity distribution using the TX system for AC showed similar results compared to the reference (<5% difference in hot regions) and outperformed the MR‐based methods as implemented in the PET/MRI system (<10% difference in hot regions). However, the additional hardware of the TX system adds complexity to the acquisition process.ConclusionOur porcine study demonstrates the feasibility of post‐injection transmission scans using the developed TX system in a clinical setting. This makes it a useful tool for PET/MRI in cases where transmission information is needed for AC. Potential applications are studies using larger animals where state‐of‐the‐art atlas‐based or artificial intelligence AC methods are not available.

MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF in gliomas: a stereotactic image-based histological validation study.

To investigate the effects of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status of gliomas on O-(2-18F-fluoroethyl)-L-tyrosine ([18F]FET) uptake and cerebral blood flow (CBF) of arterial spin labeling (ASL), evaluated by hybrid PET/MR. Stereotactic biopsy was used to validate the findings. A set of whole tumor and reference volumes of interest (VOIs) based on PET/FLAIR imaging were delineated and transferred to the corresponding [18F]FET PET and CBF maps in 57 patients with newly diagnosed gliomas. The mean and max tumor-to-brain ratio (TBR) and normalized CBF (nCBF) were calculated. The predictive efficacy of [18F]FET PET and CBF in determining MGMT promoter methylation status of glioma were evaluated by whole tumor analysis and stereotactic biopsy. The correlation between PET/MR parameters and MGMT promoter methylation were analyzed using histological specimens acquired from multiple stereotactic biopsies. Based on the analysis of whole tumor volume and biopsy site, TBRmean, TBRmax, nCBFmean, and nCBFmax showed no statistically significant differences between gliomas with and without MGMT promoter methylation (all p > 0.05). Furthermore, stereotactic biopsy demonstrated that TBRmean, TBRmax, nCBFmean, and nCBFmax showed no correlation with MGMT promoter methylation (r = -0.117, p = 0.579; r = -0.161, p = 0.443; r = -0.271, p = 0.191; r = -0.300, p = 0.145; respectively). MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. Stereotactic biopsy validates it and further reveals there is no correlation of [18F]FET PET uptake and CBF with the percentages of MGMT promoter methylation. • Based on whole tumor VOI assessment, MGMT promoter methylation status shows no effect on [18F]FET uptake and CBF of ASL in gliomas. • For WHO grade IV glioblastomas, [18F]FET PET and ASL parameters based on hybrid PET/MR fail to predict the MGMT promoter methylation status. • Stereotactic image-based histology reveals that there is no correlation of [18F]FET PET uptake and CBF with the status and percentages of MGMT promoter methylation in gliomas.

Kinetics of PSMA PET uptake in prostate cancer lesions after radiation therapy: A single-center retrospective study.

36 Background: The kinetics of PSMA PET uptake in prostate cancer lesions after radiation therapy (RT) is unknown. The aim of this study was to assess the patterns of PSMA PET uptake in irradiated lesions using serial PSMA PET/CT scans. Methods: This was a single-center retrospective study that included patients with prostate cancer who underwent one PSMA PET/CT scan before RT and at least one other scan after RT between November 2016 and July 2021. One reader (M.H.) analyzed the target lesions uptake by visual criteria (uptake above background) and semi-quantitative analysis. Lesions with and without residual uptake were compared for 1) time-interval after RT, 2) lesion tissue type (prostate, prostate bed, lymph node, and bone), 3) RT type (stereotactic body RT, intensity-modulated RT, three-dimensional conformal RT, and proton therapy), 4) baseline uptake intensity (SUVmax), and 5) PSMA-derived tumor volume (PSMA-TV). Lesions with residual uptake were followed-up. Diagnosis of recurrence was made by biopsy or subsequent PSMA PET/CT where increased PSMA uptake from the previous scan was considered a recurrence. Results: A total of 108 patients with available clinical and imaging data on 257 irradiated lesions (lymph node: n = 126; bone: n = 98; prostate: n = 25; prostate bed: n = 8) were included. The median time from end of RT to follow-up PET was 10.6 (range: 0.4-51.7) months. Residual uptake after RT was observed in 90/257 (35.0%) of the irradiated lesions. The mean decrease in SUVmax on the follow-up PET performed at &lt; 3, 3-6, 6-9, and 9-12 months post-RT were 41.4%, 53.8%, 65.6%, and 69.7% (p = 0.004). Residual uptake was more commonly seen in the prostate (prostate 68.0%; bone 40.8%; prostate bed 25.0%; lymph node 24.8%, p &lt; 0001), and associated with higher baseline uptake and lesion size: (residual uptake pos. vs neg.) SUVmax 9.5 vs 6.4, p &lt; 0.001; PSMA-TV 1.7 vs 1.0 ml, p = 0.002. In multivariate logistic regression analysis, shorter time after RT, higher baseline SUVmax, and target lesions in the prostate were independently associated with residual uptake. Among the lesions with residual uptake, 28/90 (31.1%) lesions were subsequently evaluated by biopsy and/or follow-up PSMA PET, and 6/28 (21.4%) lesions were eventually diagnosed as recurrence. Risk factors of recurrence were a residual uptake observed after a long time-interval from the end of RT (recurrence vs non-recurrence: 15.8 vs 3.7 months, p = 0.002) in the prostate lesion (prostate 50.0%; bone 12.5%; lymph node 0.0%, p = 0.044). When using a cutoff value of &gt; 8.6 months after RT, the presence of residual uptake was diagnostic of recurrence with a sensitivity of 0.83 and specificity of 0.86 (AUC: 0.92). Conclusions: The PSMA PET uptake of irradiated lesion decreases gradually over one year, while the uptake in the prostate tends to remain longer than in bone and lymph node lesions. A persistent uptake 9-12 months after RT is highly suggestive of recurrence.

18F-fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma.

Positron emission tomography is a useful technique for diagnosing lymph node (LN) metastasis. This study aimed to elucidate the association between fluorodeoxyglucose accumulation and the microenvironment in metastatic LNs in lung adenocarcinoma. We retrospectively analyzed 62 patients with surgically resected pathological N2 lung adenocarcinoma who underwent preoperative PET. The maximum standardized uptake value (SUVmax) in the metastatic LNs was measured. Lymph node specimens were immunohistochemically analyzed for CD8+, FoxP3+, and CD79a+ lymphocytes, CD204+ tumor‐associated macrophages (TAMs), and alpha‐smooth muscle actin‐positive cancer‐associated fibroblasts (αSMA+ CAFs). We compared the clinicopathologic and immunohistochemical characteristics between two groups with high and low LN SUVmax. Using novel 3D hybrid spheroid models, we investigated the change in invasiveness of cancer cells in the presence of CAFs. In the multivariate analyses, LN SUVmax was an independent prognostic factor. The overall survival in the LN SUVmax high group was significantly worse than in the low group (P = .034). In the LN SUVmax high group, metastatic cancer cell invasion of extranodal tissue was more frequent (P = .005) and the number of CD204+ TAMs and αSMA+ CAFs in metastatic LNs was significantly higher than in the low group (P < .001 and P = .002, respectively). Hybrid spheroid models revealed that cancer cells coexisting with CAFs were more invasive than those without CAFs. Our results indicated a strong association between LN SUVmax and poor prognosis in patients with N2 lung adenocarcinoma. Moreover, LN SUVmax was suggested to be associated with the presence of tumor‐promoting stromal cells in metastatic LNs.

PET-Based Radiogenomics Supports mTOR Pathway Targeting for Hepatocellular Carcinoma.

This work aimed to explore in depth the genomic and molecular underpinnings of hepatocellular carcinoma (HCC) with increased 2[18F]fluoro-2-deoxy-d-glucose (FDG) uptake in PET and to identify therapeutic targets based on this imaging-genomic surrogate. We used RNA sequencing and whole-exome sequencing data obtained from 117 patients with HCC who underwent hepatic resection with preoperative FDG-PET/CT imaging as a discovery cohort. The primary radiogenomic results were validated with transcriptomes from a second cohort of 81 patients with more advanced tumors. All patients were allocated to an FDG-avid or FDG-non-avid group according to the PET findings. We also screened potential drug candidates targeting FDG-avid HCCs in vitro and in vivo. High FDG avidity conferred worse recurrence-free survival after HCC resection. Whole transcriptome analysis revealed upregulation of mTOR pathway signals in the FDG-avid tumors, together with higher abundance of associated mutations. These clinical and genomic findings were replicated in the validation set. A molecular signature of FDG-avid HCCs identified in the discovery set consistently predicted poor prognoses in the public-access datasets of two cohorts. Treatment with an mTOR inhibitor resulted in decreased FDG uptake followed by effective tumor control in both the hyperglycolytic HCC cell lines and xenograft mouse models. Our PET-based radiogenomic analysis indicates that mTOR pathway genes are markedly activated and altered in HCCs with high FDG retention. This nuclear imaging biomarker may stimulate umbrella trials and tailored treatments in precision care of patients with HCC.

Integrated PET/MRI With 68Ga-DOTATATE and 18F-FDG in Pheochromocytomas and Paragangliomas: An Initial Study.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors with metastatic potential. Both 68Ga-DOTATATE and 18F-FDG PET/CT scans have been demonstrated to have important roles in imaging PPGLs, but less is known about the performance of PET/MRI for PPGLs. The study is aimed to investigate whether diffusion-weighted imaging-MRI (DWI-MRI) has an added value to PET imaging in the identification of PPGL lesions by means of integrated PET/MRI. Eleven patients who underwent both 18F-FDG and 68Ga-DOTATATE PET/MRI within 2 weeks were retrospectively included in the study. A total of 56 PPGL lesions were analyzed, and lesion-based detection rates of 68Ga-DOTATATE PET, 18F-FDG PET, DWI-MRI, and PET/MRI were calculated and compared, respectively. 68Ga-DOTATATE PET was superior to 18F-FDG PET and DWI-MRI in imaging PPGLs with a lesion-based detection rate of 96.4% (54/56) (95% confidence interval [CI], 87.7%-99.6%), 85.7% (48/56) (95% CI, 76.3%-95.2%), and 89.3% (50/56) (95% CI, 80.9%-97.6%), respectively. PET/MRI with DWI could improve the detection rate of 68Ga-DOTATATE and 18F-FDG PET alone up to 100% in metastatic PPGLs. Lesions of PPGL demonstrated markedly higher tracer uptake in 68Ga-DOTATATE PET than in 18F-FDG PET (P = 0.009 for primary lesion, P = 0.033 for metastases). 68Ga-DOTATATE PET showed a higher detection rate than 18F-FDG for PPGLs. In integrated PET/MRI, MRI had an added value to 18F-FDG PET but not much to 68Ga-DOTATATAE PET in identifying PPGL lesions.

Decreased Gray—White Matter Contrast of [11C]-PiB Uptake in Cognitively Unimpaired Subjects with Severe Obstructive Sleep Apnea

BackgroundVery recently, cognitively normal, middle-aged adults with severe obstructive sleep apnea (OSA) were shown to have regional cortical amyloid-β deposits. In the normal brain, amyloid tracer (e.g., [11C]-PiB) uptake is observed in white matter (WM) but not in cortical gray matter (GM), resulting in clear GM—WM contrast. There are no reports on possible changes in this contrast in severe OSA.ObjectivesEvaluate changes in the global [11C]-PiB GM—WM contrast and study if factors reflecting clinical and imaging characteristics are associated with them.Design and SettingCross-sectional imaging study.Participants19 cognitively intact middle-aged (mean 44 years) patients with severe OSA (Apnea—Hypopnea Index >30/h), carefully selected to exclude any other possible factors that could alter brain health.MeasurementsDetailed neuroimaging (amyloid PET, MRI). Signs of possible alterations in amyloid tracer GM—WM contrast and kinetics were studied with static and dynamic [11C]-PiB PET and WM structures with detailed 3.0T MRI.ResultsStatic [11C]-PiB PET uptake showed significantly decreased GM—WM contrast in 5 out of 19 patients. This was already clearly seen in visual evaluation and also detected quantitatively using retention indexes. Dynamic imaging revealed decreased contrast due to alterations in trace accumulation in the late phase of [11C]-PiB kinetics. Decreased GM—WM contrast in the late phase was global in nature. MRI revealed no corresponding alterations in WM structures. Importantly, decreased GM—WM contrast was associated with smoking (p = 0.007) and higher Apnea—Hypopnea Index (p = 0.001).ConclusionsSevere OSA was associated with decreased GM—WM contrast in amyloid tracer uptake, with significant correlation with clinical parameters of smoking and AHI. The results support and further extend the current understanding of the deleterious effect of severe OSA on proper amyloid clearance, possibly reflecting dysfunction of the brain glymphatic system.

Diagnostic performance of a novel high-resolution dedicated axillary PET system in the assessment of regional nodal spread of disease in early breast cancer.

In early breast cancer, a non-invasive method with higher sensitivity and negative predictive value (NPV) is needed to identify and recognize more indolent axillary lymph nodes (ALNs). This study aimed to assess whether a novel high-resolution dedicated ALN positron emission tomography (LymphPET) system could improve sensitivity in detecting early breast cancer (clinical N0-N1 stage). A total of 103 patients with clinical stage T1-2N0-1M0 breast cancer were evaluated by 18F-fluorodeoxyglucose (18F-FDG) LymphPET. The maximum single-voxel PET uptake value of ALNs (maxLUV) and the tumor-to-background ratio (TBR) for fat (TBR1) and muscle (TBR2) tissue were calculated. Then, 78 patients with cN0 stage breast cancer received sentinel lymph node biopsy alone or combined with axillary lymph node dissection (ALND), and 25 patients with cN1 stage breast cancer underwent fine-needle aspiration. A total of 99 invasive breast carcinoma cases were included in this study. The diagnostic sensitivity of LymphPET was 88%, specificity was 79%, false-negative rate was 12%, the false-positive rate was 21%, positive predictive value was 75%, NPV was 90%, and accuracy was 83%. The maxLUV was superior to TBR1 and TBR2 in detecting ALNs, with 0.27 being the most optimal cutoff value. The 18F-FDG LymphPET system can be used to identify and recognize more indolent ALNs of breast cancer due to greater sensitivity and a much higher NPV.

Machine Learning Quantitative Analysis of FDG PET Images of Medial Temporal Lobe Epilepsy Patients.

18F-FDG PET is widely used in epilepsy surgery. We established a robust quantitative algorithm for the lateralization of epileptogenic foci and examined the value of machine learning of 18F-FDG PET data in medial temporal lobe epilepsy (MTLE) patients. We retrospectively reviewed patients who underwent surgery for MTLE. Three clinicians identified the side of MTLE epileptogenesis by visual inspection. The surgical side was set as the epileptogenic side. Two parcellation paradigms and corresponding atlases (Automated Anatomical Labeling and FreeSurfer aparc + aseg) were used to extract the normalized PET uptake of the regions of interest (ROIs). The lateralization index of the MTLE-associated regions in either hemisphere was calculated. The lateralization indices of each ROI were subjected for machine learning to establish the model for classifying the side of MTLE epileptogenesis. Ninety-three patients were enrolled for training and validation, and another 11 patients were used for testing. The hit rate of lateralization by visual analysis was 75.3%. Among the 23 patients whose MTLE side of epileptogenesis was incorrectly determined or for whom no conclusion was reached by visual analysis, the Automated Anatomical Labeling and aparc + aseg parcellated the associated ROIs on the correctly lateralized MTLE side in 100.0% and 82.6%. In the testing set, lateralization accuracy was 100% in the 2 paradigms. Visual analysis of 18F-FDG PET to lateralize MTLE epileptogenesis showed a lower hit rate compared with machine-assisted interpretation. While reviewing 18F-FDG PET images of MTLE patients, considering the regions associated with MTLE resulted in better performance than limiting analysis to hippocampal regions.

Positron emission tomography-magnetic resonance imaging as a research tool in musculoskeletal conditions.

Compared to positron emission tomography/computed tomography (PET/CT), the uptake of PET- magnetic resonance imaging (MRI) has been slow, even more so in clinical practice compared to the (pre-)clinical research setting. However, for applications in musculoskeletal (MSK) research, the combination of PET and MRI into a single modality offers attractive advantages over other imaging modalities. Most importantly, MRI has exquisite soft-tissue detail without the use of contrast agents or ionizing radiation, superior bone marrow visualization, and an extensive spectrum of distinct multiparametric assessment methods. In the preclinical setting, the introduction of PET inserts for small-animal MRI machines has proven to be a successful concept in bringing this technology to the lab. Initial hurdles in quantification have been mainly overcome in this setting. In parallel, a promising range of radiochemistry techniques has been developed to create multimodality probes that offer the possibility of simultaneously querying different metabolic pathways. Not only will these applications help in elucidating disease mechanisms, but they can also facilitate drug development. The clinical applications of PET/MRI in MSK are still limited, but encouraging initial results with novel radiotracers suggest a high potential for use in various MSK conditions, including osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and inflammation and infection. Further innovations will be required to bring down the cost of PET/MRI to justify a broader clinical implementation, and remaining issues with quality control and standardization also need to be addressed. Nevertheless, PET/MRI is a powerful platform for MSK research with distinct qualities that are not offered by other techniques.

Fluorescence real-time kinetics of protoporphyrin IX after 5-ALA administration in low-grade glioma.

5-Aminolevulinic acid (5-ALA) induces fluorescence in high-grade glioma (HGG), which is used for resection. However, the value of 5-ALA-induced fluorescence in low-grade glioma (LGG) is unclear. Time dependency and time kinetics have not yet been investigated. The purpose of this study was to investigate real-time kinetics of protoporphyrin IX (PpIX) in LGG based on hyperspectral fluorescence-based measurements and identify factors that predict fluorescence. Patients with grade II gliomas and imaging from which HGGs could not be completely ruled out received 5-ALA at 20 mg/kg body weight 4 hours prior to surgery. Fluorescence intensity (FI) and PpIX concentration (CPpIX) were measured in tumor tissue utilizing a hyperspectral camera. Apparent diffusion coefficient (ADC)-based tumor cell density, Ki-67/MIB-1 index, chromosomal 1p/19q codeletion, and 18F-fluoroethyl-l-tyrosine (18F-FET) PET values and their role for predicting fluorescence were evaluated. Eighty-one biopsies from 25 patients were included. Tissues with fluorescence demonstrated FI and CPpIX maxima between 7 and 8 hours after administration. When visible fluorescence was observed, peaks of FI and CPpIX were observed within this 7- to 8-hour time frame, regardless of any MRI gadolinium contrast enhancement. Gadolinium enhancement (p = 0.008), Ki-67/MIB-1 index (p < 0.001), 18F-FET PET uptake ratio (p = 0.004), and ADC-based tumor cellularity (p = 0.017) significantly differed between fluorescing and nonfluorescing tissue, but not 1p/19q codeletions. Logistic regression demonstrated that 18F-FET PET uptake and Ki-67/MIB-1 index were independently related to fluorescence. This study reports a fluorescence-based assessment of CPpIX in human LGG tissues related to 18F-FET PET uptake and Ki-67/MIB-1. As in HGGs, fluorescence in LGGs peaked between 7 and 8 hours after 5-ALA application, which has consequences for the timing of administration.

18F-FDG PET as an imaging biomarker for the response to FGFR-targeted therapy of cancer cells via FGFR-initiated mTOR/HK2 axis.

Rationale: The overall clinical response to FGFR inhibitor (FGFRi) is far from satisfactory in cancer patients stratified by FGFR aberration, the current biomarker in clinical practice. A novel biomarker to evaluate the therapeutic response to FGFRi in a non-invasive and dynamic manner is thus greatly desired.Methods: Six FGFR-aberrant cancer cell lines were used, including four FGFRi-sensitive ones (NCI-H1581, NCI-H716, RT112 and Hep3B) and two FGFRi-resistant ones (primary for NCI-H2444 and acquired for NCI-H1581/AR). Cell viability and tumor xenograft growth analyses were performed to evaluate FGFRi sensitivities, accompanied by corresponding 18F-fluorodeoxyglucose (18F-FDG) uptake assay. mTOR/PLCγ/MEK-ERK signaling blockade by specific inhibitors or siRNAs was applied to determine the regulation mechanism.Results: FGFR inhibition decreased the in vitro accumulation of 18F-FDG only in four FGFRi-sensitive cell lines, but in neither of FGFRi-resistant ones. We then demonstrated that FGFRi-induced transcriptional downregulation of hexokinase 2 (HK2), a key factor of glucose metabolism and FDG trapping, via mTOR pathway leading to this decrease. Moreover, 18F-FDG PET imaging successfully differentiated the FGFRi-sensitive tumor xenografts from primary or acquired resistant ones by the tumor 18F-FDG accumulation change upon FGFRi treatment. Of note, both 18F-FDG tumor accumulation and HK2 expression could respond the administration/withdrawal of FGFRi in NCI-H1581 xenografts correspondingly.Conclusion: The novel association between the molecular mechanism (FGFR/mTOR/HK2 axis) and radiological phenotype (18F-FDG PET uptake) of FGFR-targeted therapy was demonstrated in multiple preclinical models. The adoption of 18F-FDG PET biomarker-based imaging strategy to assess response/resistance to FGFR inhibition may benefit treatment selection for cancer patients.

Independent Prognostic Utility of 11C-Pittsburgh Compound B PET in Patients with Light-Chain Cardiac Amyloidosis.

11C-Pittsburgh compound B (PiB) PET/CT visualizes the amount of myocardial amyloid deposit and can be used to prognosticate patients with amyloid light-chain (AL) cardiac amyloidosis (CA). However, whether 11C-PiB PET/CT has any independent additional prognostic value beyond the commonly used biomarkers remains unknown. Methods: This prospective study was on a cohort of 58 consecutive patients with AL CA who underwent 11C-PiB PET/CT. The patients were stratified into 2 groups on the basis of a visual assessment of whether there was myocardial 11C-PiB uptake on PET/CT. The primary endpoint was 1-y overall mortality. The independent prognostic utility of 11C-PiB PET/CT was analyzed using net reclassification improvement and integrated discrimination improvement. Results: Among the 58 patients enrolled, 35 were positive for myocardial 11C-PiB uptake on PET/CT. Patients with myocardial 11C-PiB PET uptake had a worse 1-y overall survival rate than those without (81.8% vs. 45.5%, P = 0.003 by log-rank test). In the multivariate analysis, positivity for myocardial 11C-PiB uptake on PET/CT was an independent predictor of 1-y mortality (adjusted hazard ratio, 3.382; 95% CI, 1.011-11.316; P = 0.048). In analysis of 3 subgroups of patients-those with a troponin I level of at least 0.1 ng/mL, those with an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of at least 1,800 pg/mL, and those with a difference of at least 180 mg/L between free light chains (the 3 commonly used biomarkers and their thresholds for staging in AL amyloidosis)-Kaplan-Meier curves showed for all 3 subgroups that patients positive for myocardial 11C-PiB uptake on PET/CT had a worse prognosis than those who were negative. Additionally, when the results of 11C-PiB PET/CT were added to these 3 biomarkers, the performance of 1-y mortality prediction significantly improved by net reclassification improvement (troponin I, 0.861; NT-proBNP, 0.914; difference between free light chains, 0.987) and by integrated discrimination improvement (0.200, 0.156, and 0.108, respectively). Conclusion:11C-PiB PET/CT is a strong independent predictor of 1-y overall mortality and provides incremental prognostic benefits beyond the 3 commonly used biomarkers of AL amyloidosis staging. Considering the recent development of numerous amyloid-targeting molecular imaging agents, further investigations are warranted on whether PET/CT should be included in risk stratification for patients with AL CA.

NI-8 Molecular diagnostic prediction combining T2-FLAIR mismatch sign, calcification, and methionine PET in grade II and III gliomas

Background: The 2016 WHO Classification classified grade II and III gliomas into three molecular subtypes depending on the presence of IDH mutation and 1p/19q codeletion. We combined T2-FLAIR mismatch sign, tumor calcification, and methionine PET uptake to examine whether molecular diagnosis could be predicted. Methods: 53 grade II and III glioma patients with preoperative MRI, CT, and MET-PET who underwent surgical resection or biopsy during 2000–2019 were included in this study. Out of the 53 cases, astrocytic tumors (A group: IDH-mutant, 1p19q non-codeleted) were 17, oligodendroglial tumors (O group: IDH-mutant, 1p19q codeleted) were 15, and IDH wild tumors (W group) were 21. MR and CT scans were evaluated by 3 independent reviewers to assess presence/absence of T2-FLAIR mismatch sign and calcification in the tumor, respectively. The tumor-to-normal (T/N) ratio of methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. Results: Out of the 53 cases, T2-FLAIR mismatch sign was present in 6 cases in group A and 9 cases in group W (p=0.008). Calcification in tumor was present in 2 cases in group A, 7 cases in group O, and 3 cases in group W (p=0.046). In the T2-FLAIR mismatch-positive cases, assuming MET-PET T/N>1.401 was group W and <1.401 was group A, sensitivity was 100% and specificity was 67%. In the T2-FLAIR mismatch-negative and calcification-positive cases, assuming those group O, the diagnostic predictive value was 70%. In the T2-FLAIR mismatch-negative and calcification-negative cases, assuming MET-PET T/N>2.349 was group W and <2.349 was group A or O, sensitivity was 60% and specificity was 94%. Conclusions: Combined diagnostic prediction of T2-FLAIR mismatch, calcification, and MET-PET T/N may be useful for preoperative molecular diagnosis of grade II and III gliomas.

The relationship between flutriciclamide PET uptake and grey matter atrophy in mild cognitive impairment and Alzheimer’s disease

AbstractBackgroundMicroglial activation plays a significant role in neuroinflammation in the neurodegenerative process. Microglial activation is characterised by the over‐expression of a mitochondrial protein (TSPO), that can be targeted by PET Tracers. This study aims to evaluate the relationship between [18F]GE180 PET uptake and grey matter atrophy.MethodIn this PET study, we evaluated microglial activation in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) using the novel TSPO ligand flutriciclamide ([18F]GE180). Forty‐eight participants have been assesed with [18F]GE180 PET using arterial input. Spectral analysis was used to generate parametric maps of the impulse response function at 90 minutes. Additionally, hippocampal volume analysis was performed on structural magnetic resonance images (MRIs).ResultIn a group‐wise analysis a significant reduction in hippocampal volume was found between the AD and healthy controls cohorts. Hippocampal volume significantly negatively correlated with the IRF90 in the temporal lobe and occipital lobes as well as and composite region in AD patients compared to healthy controls.ConclusionIn this [18F]GE180 PET imaging study in AD/MCI cohort, we have demonstrated that there is hippocampal atrophy when [18F]GE180 PET goes up in AD patients. The results indicate that regional [18F]GE180 PET uptake has a close association with neurodegeneration of key memories processing centre.

Cognitive reserve: Evaluating the relationship between WASI‐II Matrix Reasoning and tau accumulation using [18F]MK6240 in monolingual and bilingual individuals

AbstractBackgroundCognitive reserve (CR), a protective mechanism, allows for sustained cognitive functioning in older adults with greater experiential resources. Bilingualism, an indicator of greater cognitive reserve, has been found to preserve cognitive performance in older adults despite significant disease pathology. While the association with amyloid has been well acknowledged, the effect of tau is still under investigation. In the present study, we aim to evaluate the effect of bilingualism on individuals’ cognition and tau load.MethodThis study was conducted in 331 individuals (213 cognitively unimpaired (CU)) and 116 cognitively impaired (CI; 81 MCI and 35 AD) from the TRIAD cohort. 40% of the study participants were monolingual. Wechsler Abbreviated Scale of Intelligence ‐ Second Edition (WASI‐II) was used to measure cognitive ability and reasoning in individuals. Accumulation of tau was assessed with [18F]MK6240 PET and standardized uptake value ratio (SUVRs) were calculated between 90 to 110 min post‐injection, using cerebellum grey matter as the reference region. A voxel‐based regression model evaluated the relationship between the WASI‐II score and the PET markers [18F]MK6240, correcting for age, sex, education, APOE, diagnosis and RFT was used to account for multiple comparisons.ResultOur data showed that bilingual individuals demonstrated significantly higher scores on the Wechsler Abbreviated Scale of Intelligence ‐ Second Edition (WASI‐II) in comparison to monolingual individuals. A negative association between the cognitive score and tau accumulation was found in both monolingual and bilingual groupings. In the bilingual individuals, the associated regions were precuneus area, medial and lateral lobes. In the monolingual group, the associated regions were right frontal lobe, parietal lobe and cuneus areas.ConclusionOur results demonstrate that bilingual individuals are more resilient to the accumulation of tau; shown in higher scores in cognitive ability and reasoning despite having more regions affected than their monolingual counterparts.

18F-Sodium fluoride uptake is associated with severity of atherosclerotic stenosis in stable ischemic heart disease

BackgroundIncreased uptake of 18F-Sodium fluoride (18F-NaF) PET has potential to identify atherosclerotic plaques that are vulnerable to rupture. Whether 18F-NaF PET can evaluate the significance of atherosclerotic plaque in patients with stable coronary artery disease is less clear. We evaluated 18F-NaF PET uptake in coronary arteries in patients without acute coronary artery syndrome to determine the association of 18F-NaF signal uptake with severity of coronary stenosis. Methods and ResultsWe retrospectively identified 114 patients who received both regadenoson stress 82Rb myocardial perfusion PET and 18F-NaF PET study with an average interval of 5 months. Out of this cohort, forty-one patients underwent invasive coronary angiography. In a patient-based analysis, patients with ischemic regadenoson stress 82Rb PET had significantly higher coronary 18F-NaF uptake than patients with normal myocardial perfusion (P < .01). Among the 41 patients who underwent coronary angiography, per-vessel 18F-NaF uptake in both obstructive and nonobstructive coronary arteries was significantly higher than in normal coronary arteries (P < .05) regardless of the severity of coronary calcification. There was poor correlation between calcification and 18F-NaF uptake in coronary arteries (r = 0.41) ConclusionCoronary arterial 18F-NaF uptake is associated with coronary stenosis severity in patients with stable coronary artery disease. 18F-NaF PET studies may be useful for characterizing coronary atherosclerotic plaques.

Abstract 10440: Independent Prognostic Utility of 11 C-Pittsburgh Compound B Positron Emission Tomography in Light Chain Cardiac Amyloidosis Patients

Introduction: Recent advances in nuclear molecular imaging have allowed a more specific, non-invasive approach to the diagnosis and prognostication of cardiac amyloidosis (CA). 11 C-Pittsburgh compound B positron emission tomography/computed tomography (PiB PET/CT) is one of the widely studied nuclear molecular imaging. However, it remains to be verified whether it has any independent additional prognostic value. Hypothesis: 11 C-PiB PET/CT would have independent prognostic value in patients with light chain CA (ALCA). Methods: A prospective cohort study of 58 consecutive patients with ALCA who underwent 11 C-PiB PET/CT, were stratified into 2 groups based on a myocardial 11 C-PiB uptake or not on PET/CT. The primary and secondary outcomes were all-cause death and cardiovascular death, respectively. Results: During a median 13.6 month follow-up, 29 patients died, of which 12 died from cardiovascular events. Patients with positive 11 C-PiB PET uptake had worse event-free survival from all-cause deaths (60.5% vs. 28.7%, P =0.001) and cardiovascular deaths (84.9% vs. 58.5%, P =0.001). A positive myocardial 11 C-PiB PET/CT was an independent predictor for all-cause death (adjusted hazard ratio [aHR] 4.143, 95% confidence interval [95%CI] 1.243-13.816, P =0.021) and cardiovascular death (aHR 5.598, 95%CI 1.060-29.560, P =0.043). When 11 C-PiB PET/CT was combined with troponin I and N-terminal probrain Natriuretic Peptide, the performance of prediction significantly improved by net reclassification index of 0.872 and by integrated discrimination improvement statistics of 0.177. Conclusions: 11 C-PiB PET/CT is a strong independent predictor for all-cause and cardiovascular mortality, and provides incremental prognostic benefits in patients with ALCA. Further investigations are warranted on whether PET/CT should be included in the risk stratification for the ALCA patients