fluoro-2-deoxy-D-glucose Positron Emission Tomography Research Articles

Modulation of FDG Uptake by Cell Cycle Synchronization Using a T-Type Calcium Channel Inhibitor.

We investigated whether cell cycle synchronization induced by the T-type calcium channel inhibitor mibefradil could increase tumoral 2-[18F] fluoro-2-deoxy-d-glucose (FDG) uptake in vitro and in vivo. Human prostate cancer cells (PC-3) were treated with 10 μM mibefradil for 24, 48, and 72 h to induce G1 arrest. Cell cycle distribution was analyzed at 0, 4, 8, 12, 15, 18, and 24 h after mibefradil withdrawal. Cellular uptake was measured after incubating cells with [3H] Deoxy-d-Glucose (DDG) for 1 h at the same time points used in the cell cycle analysis. The correlation between [3H] DDG uptake and each cell cycle phase was evaluated in the early (0-12 h) and late phases (15-24 h) of synchronization. In vivo FDG PET imaging was performed in PC-3-bearing mice at baseline, 24 h, and 48 h after mibefradil treatment. The G0/G1 fraction of PC-3 cells was significantly increased from 33.1% ± 0.2% to 60.9% ± 0.8% after 24 h mibefradil treatment, whereas the S and G2/M fractions were decreased from 36.3% ± 1.4% to 23.2% ± 1.1% and from 29.7% ± 1.3% to 14.9% ± 0.9%, respectively, which were similar to the results by serum starvation. Mibefradil treatment for 24, 48, and 72 h increased the number of cells in S phase at 18-24 h after withdrawal; however, only the 72 h treatment increased [3H] DDG uptake (145.8 ± 5.8% of control at 24 h after withdrawal). [3H] DDG uptake was positively correlated with the size of the S phase fraction and negatively correlated with the size of the G0/G1 fraction in the late phase of synchronization. DDG uptake was significantly increased by mibefradil-induced cell cycle synchronization and correlated with the sizes of cell cycle fractions. In vivo FDG PET imaging also demonstrated a significant increase in tumor uptake after mibefradil treatment. Quantified tumor FDG uptake (%ID/g) increased from 4.13 ± 2.10 to 4.7 ± 2.16 at 24 h, and 5.95 ± 2.57 at 48 h (p < 0.05). Cell cycle synchronization could be used to increase the diagnostic sensitivity of clinical FDG positron emission tomography.

Relationships of 18F-FDG PET with tumor microenvironment immunotypes, especially PD-L1 and CD15 expression, and prognosis in oral squamous cell carcinoma

BackgroundThe relationship between 2-[18F]-fluoro-2-deoxy-d-glucose–positron emission tomography (FDG-PET) findings and programmed death ligand-1 (PD-L1) expression has been reported in several cancers. We investigated the correlations of FDG uptake with immune cell counts, including myeloid-derived suppressor cells (MDSCs), and PD-L1 expression in the tumor microenvironment. We examined 72 patients with oral squamous cell carcinoma (OSCC) with immunohistochemistry data for PD-L1, CD8, S100A8, CD15, and CD33. We used the maximum standardized uptake value (SUVmax) to reflect FDG uptake in each patient.ResultsHigh SUVmax and high MDSC counts were associated with poor prognosis. Significantly higher SUVmax was found in patients with high PD-L1 expression and in those with a high CD15+ cell density (P = 0.03 and P = 0.02, respectively). In multiple regression analysis, the tumor size had the greatest effect on SUVmax (P < 0.001), followed by PD-L1 (P = 0.014), and when the tumor size was excluded, CD15 (P = 0.02) was included in the prediction equation. FDG uptake in some cold tumor subgroups, low PD-L1 expression, and a low CD8+ cell density was linked to significantly lower SUVmax than the other variables. High SUVmax was clearly associated with high PD-L1 expression and/or a high CD15+ cell density.ConclusionsFDG uptake was affected by PD-L1 expression and the density of CD15+ cells in cancer tissue. FDG-PET may illuminate the tumor microenvironment immunotypes before biopsy or resection.

Correlation of 18F-FDG PET/CT metabolic parameters with the expression of immune biomarkers in the tumour microenvironment in lung adenocarcinoma

To explore the association between metabolic parameters evaluated by integrated 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT) and the expression of immune biomarkers in the tumour microenvironment in lung adenocarcinoma. This study included 134 patients. Metabolic parameters were obtained by PET/CT. Immunohistochemistry analysis was used for FOXP3-TILs (transcription factor forkhead box protein 3 tumour-infiltrating lymphocytes), CD8-TILs, CD4-TILs, CD68-TAMs (tumour-associated macrophages) and galectin-1 (Gal-1) tumour expression. There were significant positive associations between FDG PET metabolic parameters and the median percentage of immune reactive areas (IRA%) covered by FOXP3-TILs and CD68-TAMs. Negative associations with the median IRA% covered by CD4-TILs and CD8-TILs were observed: maximal standardised uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG), and IRA% for FOXP3-TILs (rho=0.437, 0.400, 0.414; p<0.0001 for all parameters); SUVmax, MTV, TLG, and IRA% for CD68-TAMs (rho=0.356, 0.355, 0.354; p<0.0001 for all parameters); SUVmax, MTV, TLG, and IRA% for CD4-TILs (rho=-0.164, -0.190, -0.191; p=0.059, 0.028, 0.027, respectively); SUVmax, MTV, TLG, and IRA% for CD8-TILs (rho=-0.305, -0.316, -0.322; p<0.0001 for all parameters). There were significant positive associations between tumour Gal-1 expression and the median IRA% covered by FOXP3-TILs and CD68-TAMs (rho=0.379; p<0.0001; rho=0.370; p<0.0001, respectively), and a significant negative association with the median IRA% covered by CD8-TILs (rho=-0.347; p<0.0001) was observed. Tumour stage (p=0.008), Gal-1 expression (p=0.008), and median IRA% covered by CD8-TILs (p=0.054) were independent risk factors for overall survival. FDG PET may facilitate a comprehensive evaluation of the tumour microenvironment and predict response to immunotherapy.

Sporadic Creutzfeldt-Jakob disease is associated with reorganization of metabolic connectivity in a pathological brain network.

Although sporadic Creutzfeldt-Jakob disease (sCJD) is a rare cause of dementia, it is critical to understand its functional networks as the prion protein spread throughout the brain may share similar mechanisms with other more common neurodegenerative disorders. In this study, the metabolic brain network associated with sCJD was investigated and its internal network organization was explored. We explored 2-[18 F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) brain scans of 29 sCJD patients, 56 normal controls (NCs) and 46 other dementia patients from two independent centers. sCJD-related pattern (CJDRP) was identified in a cohort of 16 pathologically proven sCJD patients and 16 age-matched NCs using scaled subprofile modeling/principal component analysis and was prospectively validated in an independent cohort of 13 sCJD patients and 20 NCs. The pattern's specificity was tested on other dementia patients and its clinical relevance by clinical correlations. The pattern's internal organization was further studied using graph theory methods. The CJDRP was characterized by relative hypometabolism in the bilateral caudate, thalami, middle and superior frontal gyri, parietal lobe and posterior cingulum in association with relative hypermetabolism in the hippocampi, parahippocampal gyri and cerebellum. The pattern's expression significantly discriminated sCJD from NCs and other dementia patients (p < 0.005; receiver operating characteristic analysis CJD vs. NCs area under the curve [AUC]0.90-0.96, sCJD vs. Alzheimer's disease AUC0.78, sCJD vs. behavioral variant of frontotemporal dementia AUC0.84). The pattern's expression significantly correlated with cognitive, functional decline and disease duration. The metabolic connectivity analysis revealed inefficient information transfer with specific network reorganization. The CJDRP is a robust metabolic biomarker of sCJD. Due to its excellent clinical correlations it has the potential to monitor disease in emerging disease-modifying trials.

The Relationship between Preoperative FDG PET/CT Uptake and Survival in Patients with Lung Cancer

IntroductionDespite all advances in diagnosis and treatment, lung cancer is the leading cause of cancer death in both sexes worldwide. Because of the different survival rates in lung cancer, additional factors are needed to determine prognosis. In this study, we aimed to investigate the relationship between survival and clinical data of primary tumor SUV (Standardized Uptake Value) to evaluate the role of FDG-PET ([18F]-fluoro-2-deoxy-D-glucose Positron Emission Tomography) as a prognostic factor in lung cancer.Material and methodsThe data of patients who underwent anatomic resection and preoperative positron emission tomography/computed tomography (PET/CT) were performed retrospectively between February 2006 and October 2019 in the Department of Thoracic Surgery, Faculty of Medicine, Gaziantep University.ResultsAll cases were 666 patients, 64 of whom (9.6%) were females and 602 of them (90.4%) were males. The mean age of the patients was 61.91±9.6 years. Histologically, there were 369 (55.4%) epidermoid carcinomas, 233 (34.9%) adenocarcinomas. The overall mean survival was 68.2 months and the median survival was 63.6 months. The mean mass SUV values of the patients were 13.73 ± 6.65. The effect of histological type, TNM stage, metastasis and recurrence on survival was statistically significant (p &lt; 0.05). According to the univariate analysis (Cox regression analysis), it was found that 1 unit increase in SUV value contributed to a statistically significant increase in mortality risk (p = 0.002, HR: 1.024, 95% CI: 1.009-1.040).ConclusionsIn our study on 666 patients, unlike literature, no statistically significant relationship was found between SUV value and survival.

Metabolic imaging with FDG-PET and time to progression in patients discontinuing immune-checkpoint inhibition for metastatic melanoma

BackgroundThe optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Active residual disease is considered prohibitive for treatment discontinuation and its detection by diagnostic CT imaging is limited. Here, we set out to determine the potential added value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to identify patients at higher risk of relapse following discontinuation of ICB in advanced melanoma.MethodsMetastatic melanoma patients who discontinued ICB were identified retrospectively. Eligible patients received FDG-PET and diagnostic CT within four months of ICB discontinuation. We defined morphologic response using RECIST v1.1. Complete metabolic response (CMR) was defined as uptake in tumor lesions below background, whereas any site of residual, FDG-avid disease was rated as non-CMR. The primary endpoint was time to progression (TTP) after therapy discontinuation stratified by morphologic and metabolic imaging response using Kaplan–Meier estimates and log-rank test.ResultsThiry-eight patients were eligible for this analysis. Median follow-up was 37.3 months since ICB discontinuation. Median TTP in the overall cohort was not reached. A greater proportion of patients were rated as CMR in PET (n = 34, 89.5%) as compared to complete response (CR) in CT (n = 13, 34.2%). Median TTP was reached in patients with non-CMR (12.7 months, 95%CI 4.4-not reached) but not for patients with CMR (log-rank: p < 0.001). All patients with complete response by CT had CMR by PET. In a subset of patients excluding those with complete response by CT, TTP remained significantly different between CMR and non-CMR (log-rank: p < 0.001).ConclusionAdditional FDG-PET at time of discontinuation of ICB therapy helps identify melanoma patients with a low risk of recurrence and favourable prognosis compared to CT imaging alone. Results may have clinical relevance especially for patients with residual tumor burden.

Impaired self-awareness of cognitive deficits in Parkinson's disease relates to cingulate cortex dysfunction.

Impaired self-awareness of cognitive deficits (ISAcog) has rarely been investigated in Parkinson's disease (PD). ISAcog is associated with poorer long-term outcome in other diseases. This study examines ISAcog in PD with and without mild cognitive impairment (PD-MCI), compared to healthy controls, and its clinical-behavioral and neuroimaging correlates. We examined 63 PD patients and 30 age- and education-matched healthy controls. Cognitive state was examined following the Movement Disorder Society Level II criteria. ISAcog was determined by subtracting z-scores (based on controls' scores) of objective tests and subjective questionnaires. Neural correlates were assessed by structural magnetic resonance imaging (MRI) and 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography (FDG-PET) in 47 patients (43 with MRI) and 11 controls. We analyzed whole-brain glucose metabolism and cortical thickness in regions where FDG-uptake correlated with ISAcog. PD-MCI patients (N = 23) showed significantly more ISAcog than controls and patients without MCI (N = 40). When all patients who underwent FDG-PET were examined, metabolism in the bilateral superior medial frontal gyrus, anterior and midcingulate cortex negatively correlated with ISAcog (FWE-corrected p < 0.001). In PD-MCI, ISAcog was related to decreased metabolism in the right superior temporal lobe and insula (N = 13; FWE-corrected p = 0.023) as well as the midcingulate cortex (FWE-corrected p = 0.002). Cortical thickness was not associated with ISAcog in these regions. No significant correlations were found between ISAcog and glucose metabolism in controls and patients without MCI. Similar to Alzheimer's disease, the cingulate cortex seems to be relevant in ISAcog in PD. In PD-MCI patients, ISAcog might result from a disrupted network that regulates awareness of cognition and error processes.

Surgical intervention as a curative major for secondary hypertension

Retroperitoneal functional paraganglioma is a rare type of neuroendocrine neoplasm which secrete excess catecholamines including epinephrine, norepinephrine, dopamine and their metabolites metanephrine, normetanephrine, 3-methoxytyramine respectively. Early diagnosis of functional paraganglioma is important because its removal is often curative. The extent of disease is evaluate using 2(18F)-fluoro-2 deoxy-D-glucose positron emission tomography (FDG-PET), where increased uptake of 18-FDG observed the mass. It is one of the rare curable causes of secondary hypertension. Here, we have presented the rare case of a young female who was recently diagnosed with hypertension and pain in abdomen, was later found to have functional paraganglioma.

Hypoxia and glucose metabolism assessed by FMISO and FDG PET for predicting IDH1 mutation and 1p/19q codeletion status in newly diagnosed malignant gliomas

BackgroundTumor hypoxia and glycolysis have been recognized as determinant factors characterizing tumor aggressiveness in malignant gliomas. To clarify in vivo hypoxia and glucose metabolism in relation to isocitrate dehydrogenase (IDH) mutation and chromosome 1p and 19q (1p/19q) codeletion status, we retrospectively analyzed hypoxia as assessed by positron emission tomography (PET) with [18F]-fluoromisonidazole (FMISO) and glucose metabolism as assessed by PET with [18F]-fluoro-2-deoxy-d-glucose (FDG) in newly diagnosed malignant gliomas.MethodsIn total, 87 patients with newly diagnosed supratentorial malignant (WHO grade III and IV) gliomas were enrolled in this study. They underwent PET studies with FMISO and FDG before surgery. The molecular features and histopathological diagnoses based on the 2016 WHO classification were determined using surgical specimens. Maximal tumor-to-normal ratio (TNR) was calculated for FDG PET, and maximal tumor-to-blood SUV ratio (TBR) was calculated for FMISO PET. The PET uptake values in relation to IDH mutation and 1p/19q codeletion status were statistically analyzed.ResultsIn all tumors and malignant astrocytomas, the median FMISO TBR in IDH-wildtype tumors was significantly higher than that in IDH-mutant tumors (P < 0.001 and P < 0.01, respectively). In receiver operating characteristic (ROC) analysis, the area under the curve showed that the sensitivity for the discrimination was moderate (0.7–0.8) and the specificity was low (0.65–0.68). In the same population, the median FDG TNR in IDH-wildtype tumors tended to be higher than that in IDH-mutant tumors, but the difference was not statistically significant. In WHO grade III anaplastic astrocytomas, there were no significant differences in median FMISO TBR or FDG TNR between IDH-mutant and IDH-wildtype tumors. In IDH-mutant WHO grade III anaplastic gliomas, there were no significant differences in median FMISO TBR or FDG TNR between anaplastic astrocytomas and anaplastic oligodendrogliomas.ConclusionsTumor hypoxia as assessed by FMISO PET was informative for prediction of the IDH mutation status in newly diagnosed malignant gliomas. However, the accuracy of the discrimination was not satisfactory for clinical application. On the other hand, glucose metabolism as assessed by FDG PET could not differentiate the IDH-mutant status. Moreover, PET studies using FMISO and FDG could not predict IDH mutation and 1p/19q codeletion status in WHO grade III tumors.

Prediction of the treatment outcome using machine learning with FDG-PET image-based multiparametric approach in patients with oral cavity squamous cell carcinoma

To investigate the value of machine learning-based multiparametric analysis using 2-[18F]-fluoro-2-deoxy-d-glucose positron-emission tomography (FDG-PET) images to predict treatment outcome in patients with oral cavity squamous cell carcinoma (OCSCC). Ninety-nine patients with OCSCC who received pretreatment integrated FDG-PET/computed tomography (CT) were included. They were divided into the training (66 patients) and validation (33 patients) cohorts. The diagnosis of local control or local failure was obtained from patient's medical records. Conventional FDG-PET parameters, including the maximum and mean standardised uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV), and total lesion glycolysis (TLG), quantitative tumour morphological parameters, intratumoural histogram, and texture parameters, as well as T-stage and clinical stage, were evaluated by a machine learning analysis. The diagnostic ability of T-stage, clinical stage, and conventional FDG-PET parameters (SUVmax, SUVmean, MTV, and TLG) was also assessed separately. In support-vector machine analysis of the training dataset, the final selected parameters were T-stage, SUVmax, TLG, morphological irregularity, entropy, and run-length non-uniformity. In the validation dataset, the diagnostic performance of the created algorithm was as follows: sensitivity 0.82, specificity 0.7, positive predictive value 0.86, negative predictive value 0.64, and accuracy 0.79. In a univariate analysis using conventional FDG-PET parameters, T-stage and clinical stage, diagnostic accuracy of each variable was revealed as follows: 0.61 in T-stage, 0.61 in clinical stage, 0.64 in SUVmax, 0.61 in SUVmean, 0.64 in MTV, and 0.7 in TLG. A machine-learning-based approach to analysing FDG-PET images by multiparametric analysis might help predict local control or failure in patients with OCSCC.

Comparison of FDG and FMISO uptakes and distributions in head and neck squamous cell cancer tumors

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.

Positron Emission Tomography for Response Evaluation in Microenvironment-Targeted Anti-Cancer Therapy.

Therapeutic response is evaluated using the diameter of tumors and quantitative parameters of 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET). Tumor response to molecular-targeted drugs and immune checkpoint inhibitors is different from conventional chemotherapy in terms of temporal metabolic alteration and morphological change after the therapy. Cancer stem cells, immunologically competent cells, and metabolism of cancer are considered targets of novel therapy. Accumulation of FDG reflects the glucose metabolism of cancer cells as well as immune cells in the tumor microenvironment, which differs among patients according to the individual immune function; however, FDG-PET could evaluate the viability of the tumor as a whole. On the other hand, specific imaging and cell tracking of cancer cell or immunological cell subsets does not elucidate tumor response in a complexed interaction in the tumor microenvironment. Considering tumor heterogeneity and individual variation in therapeutic response, a radiomics approach with quantitative features of multimodal images and deep learning algorithm with reference to pathologic and genetic data has the potential to improve response assessment for emerging cancer therapy.

Brain FDG PET for the Etiological Diagnosis of Clinically Uncertain Cognitive Impairment During Delirium in Remission.

Positron emission tomography (PET) of the brain with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is widely used for the etiological diagnosis of clinically uncertain cognitive impairment (CUCI). Acute full-blown delirium can cause reversible alterations of FDG uptake that mimic neurodegenerative disease. This study tested whether delirium in remission affects the performance of FDG PET for differentiation between neurodegenerative and non-neurodegenerative etiology of CUCI. The study included 88 patients (82.0±5.7 y) with newly detected CUCI during hospitalization in a geriatric unit. Twenty-seven (31%) of the patients were diagnosed with delirium during their current hospital stay, which, however, at time of enrollment was in remission so that delirium was not considered the primary cause of the CUCI. Cases were categorized as neurodegenerative or non-neurodegenerative etiology based on visual inspection of FDG PET. The diagnosis at clinical follow-up after ≥12 months served as ground truth to evaluate the diagnostic performance of FDG PET. FDG PET was categorized as neurodegenerative in 51 (58%) of the patients. Follow-up after 16±3 months was obtained in 68 (77%) of the patients. The clinical follow-up diagnosis confirmed the FDG PET-based categorization in 60 patients (88%, 4 false negative and 4 false positive cases with respect to detection of neurodegeneration). The fraction of correct PET-based categorization did not differ between patients with delirium in remission and patients without delirium (86% versus 89%, p = 0.666). Brain FDG PET is useful for the etiological diagnosis of CUCI in hospitalized geriatric patients, as well as in patients with delirium in remission.

Accuracy of peritoneal carcinomatosis extent diagnosis by initial FDG PET CT in epithelial ovarian cancer: A multicentre study of the FRANCOGYN research group

IntroductionPeritoneal carcinomatosis extent in ovarian cancer is difficult to evaluate by imaging techniques even though it determines the surgical complexity and survival. The aim of this study was to estimate the accuracy of 2-[18F]-fluoro-2-deoxy-d-glucose (FDG)-PET CT (Positron-emission tomography coupled with Computerised Tomography) performed before any treatment, in the diagnosis of the extent of peritoneal carcinomatosis. We compared these results to per-operative observations/ histology samples obtained during surgery (laparotomy/ laparoscopy). Material and methodsAll women managed for an epithelial ovarian cancer between 1st January 2000 and 30th June 2016 were included if they had a FDG PET CT, before initiation of any treatment (neoadjuvant chemotherapy or frontline cytoreductive surgery). The extent of disease on histology samples from cytoreductive surgery/observations during exploratory laparoscopy were compared with the PET CT results. ResultsOver the study period, 980 women were managed for epithelial ovarian cancer, among them 90 (9.2 %) had a PET CT before any treatment. The diagnostic reliability of an ovarian lesion was 67.8 %, a colon lesion was 61.25 %, a small intestine lesion was 50.6 %, an epiploic lesion was 41.7 %, a pelvic ganglionic invasion was 62.9 % and a paraortic lymph node invasion was 61.5 %. PET CT was less effective than a standard CT examination. ConclusionPET CT is not the most effective imaging examination to estimate the extent of peritoneal carcinomatosis during the initial management of an epithelial ovarian cancer.

Impact of Interim FDG-PET (iPET) in the Outcomes of Patients with Aggressive B-Cell Lymphomas Receiving DA-EPOCH-R

Introduction: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) remains the standard of care for baseline and end of treatment scans for aggressive non-Hodgkin lymphomas (NHLs). However, the role of interim FDG-PET remains not as well defined across aggressive NHLs, especially in the era of high-intensity chemoimmunotherapy. Interim FDG-PET (iPET) can serve as an early prognostic tool, and prior studies evaluating the utility of iPET-guided treatment strategies primarily focused on diffuse large B-cell lymphomas (DLBCL) and frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Classification criteria systems assessing response also differ between studies with no clear consensus between use of Deauville criteria (DC), International Harmonization Project (IHP), and the ΔSUVmax method. Methods: This study evaluates our institutional experience with iPET during treatment with DA-EPOCH ± R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with or without Rituximab) in aggressive NHLs. We retrospectively evaluated 70 patients at Moffitt Cancer Center who started on DA-EPOCH ± R between 1/1/2014 to 12/31/2018 for aggressive NHLs. Response on interim and end-of-treatment (EOT) scans were graded per DC, IHP, and ΔSUVmax methods, and progression free survival (PFS) probability estimates were calculated with chi-square testing and Kaplan Meier method. PFS outcomes were compared between interim negative and positive scans based on each scoring method. Outcomes were also compared between groups based on interim versus EOT positive or negative scans. Results: We identified 70 patients with aggressive NHLs who received DA-EPOCH ± R at our institute. The most common diagnoses were DLBCL (61%) followed by Burkitt's lymphoma (10%), primary mediastinal B-cell lymphoma (9%), plasmablastic lymphoma (7%), gray zone lymphoma (6%), primary cutaneous large B-cell lymphoma (1%), primary effusion lymphoma (1%), and other high-grade NHL not otherwise specified (3%). Of the 43 patients with DLBCL, 21/43 (49%) had double hit lymphoma (DHL) while 7/43 (16%) had triple hit lymphoma (THL), and 3/43 (7%) had MYC-rearranged DLBCL while 2/43 (5%) had double expressor DLBCL. Thirty nine out of 70 (56%) were female, and median age at diagnosis was 58.39 years (range 22.99 - 86.86 years). Most patients had stage IV disease (49/70, 70%), and 43/70 (61%) had more than one extranodal site while 45/70 (64%) had IPI score ≥ 3. Forty-six out of 70 (66%) received central nervous system prophylaxis, most with intrathecal chemotherapy (44/70, 63%). Fifty-five out of 70 (79%) had iPET available while 6/70 (9%) had interim computerized tomography (CT) scans. Fifty-six out of 70 (80%) had EOT PET, and 4/70 (6%) had EOT CT scans. Sustained complete remission occurred in 46/70 (66%) after frontline DA-EPOCH ± R (CR1), and 12/70 (17%) were primary refractory while 5/70 (7%) had relapse after CR1. Four of 70 (6%) died before cycle 3, and 3/70 (4%) did not have long-term follow-up due to transition of care elsewhere. Median follow-up was 15.29 months (range 0.85 - 60.09 months). There was significantly better PFS observed if iPET showed DC 1-3 compared to DC 4-5 (Χ2=5.707, p=0.0169), and PFS was better if iPET was negative by IHP criteria (Χ2=4.254, p=0.0392) or ΔSUVmax method (Χ2=6.411, p=0.0113). Comparing iPET to EOT PET, there was significantly better PFS if iPET was negative with EOT PET negative (iPET-/EOT-) compared to iPET positive with EOT negative (iPET+/EOT-), and iPET+/EOT+ and iPET-/EOT+ had worse PFS after iPET-/EOT- and iPET+/EOT- respectively. This pattern in iPET/EOT PFS probability remained consistent when comparing DC (Χ2=30.041, p&lt;0.0001), IHP (Χ2=49.078, p&lt;0.0001), and ΔSUVmax method (Χ2=9.126, p=0.0104). These findings fit clinical expectations with positive EOT scans indicating primary refractory disease. There was no significant difference in PFS when comparing DLBCL versus non-DLBCL (Χ2=3.461, p=0.0628) or DHL/THL versus non-DHL/THL diagnoses (Χ2=2.850, p=0.0914). Conclusion: Our findings indicate a prognostic role of iPET during treatment with DA-EPOCH ± R for aggressive NHLs. Significant differences in PFS were seen when graded by DC, IHP, and ΔSUVmax methods used in prior studies and when comparing interim versus EOT response. Larger studies are needed to confirm these findings. Disclosures Bello: Celgene: Speakers Bureau. Shah:Novartis: Honoraria; AstraZeneca: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Sokol:EUSA: Consultancy. Chavez:Janssen Pharmaceuticals, Inc.: Speakers Bureau; Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Quantitative Analysis of [18F]FFMZ and [18F]FDG PET Studies in the Localization of Seizure Onset Zone in Drug-Resistant Temporal Lobe Epilepsy

Background: Positron emission tomography (PET) imaging in epilepsy is an in vivo technique that allows the localization of a possible seizure onset zone (SOZ) during the interictal period. Stereo-electro-encephalography (SEEG) is the gold standard to define the SOZ. The objective of this research was to evaluate the accuracy of PET imaging in localizing the site of SOZ compared with SEEG. Methods: Seven patients with refractory temporal lobe epilepsy (Ep) and 2 healthy controls (HC) underwent 2 PET scans, one with 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) and another with 2’-[¹⁸F]fluoroflumazenil (FFMZ), acquired 1 day apart. FDG was acquired for 10 min (static scan) 1 h after administration. An FFMZ scan was acquired for 60 min from radiopharmaceutical administration in a dynamic mode. Each brain PET image was segmented using a standard template implemented in PMOD 3.8. The pons was used as the reference region for modeling of the nondisplaceable binding potential (BP_ND)for FFMZ, and to obtain uptake ratios for FDG. SEEG studies of patients were performed as a part of their surgical evaluation to define the SOZ. Results: Well-defined differences between HC and Ep were found with both radiopharmaceuticals, showing the utility to identify abnormal brain regions using quantitative PET imaging. Lateralization of the SOZ findings by PET (lower uptake/binding in a specific brain hemisphere) matched in 86% for FFMZ and 71% for FDG with SEEG data. Conclusion: Quantitative PET imaging is an excellent complementary tool that matches reasonably well with SEEG to define SOZ in presurgical evaluation.

Impact of hybrid FDG-PET/CT on gross tumor volume definition of cervical esophageal cancer: reducing interobserver variation.

Intensity-modulated radiation therapy is being increasingly used to treat cervical esophageal cancer (CEC); however, delineating the gross tumor volume (GTV) accurately is essential for its successful treatment. The use of computed tomography (CT) images to determine the GTV produces a large degree of interobserver variation. In this study, we evaluated whether the use of [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/CT fused images reduced interobserver variation, compared with CT images alone, to determine the GTV in patients with CEC. FDG-PET/CT scans were obtained for 10 patients with CEC, imaged positioned on a flat tabletop with a pillow. Five radiation oncologists independently defined the GTV for the primary tumors using routine clinical data; they contoured the GTV based on CT images (GTVCT), followed by contouring based on FDG-PET/CT fused images (GTVPET/CT). To determine the geometric observer variation, we calculated the conformality index (CI) from the ratio of the intersection of the GTVs to their union. The interobserver CI was compared using Wilcoxon’s signed rank test. The mean (±SD) interobserver CIs of GTVCT and GTVPET/CT were 0.39 ± 0.15 and 0.58 ± 0.10, respectively (P = 0.005). Our results suggested that FDG-PET/CT images reduced interobserver variation when determining the GTV in patients with CEC. FDG-PET/CT may increase the consistency of the radiographically determined GTV in patients with CEC.

Relative cerebral flow from dynamic PIB scans as an alternative for FDG scans in Alzheimer's disease PET studies.

In Alzheimer’s Disease (AD) dual-tracer positron emission tomography (PET) studies with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and 11C-labelled Pittsburgh Compound B (PIB) are used to assess metabolism and cerebral amyloid-β deposition, respectively. Regional cerebral metabolism and blood flow (rCBF) are closely coupled, both providing an index for neuronal function. The present study compared PIB-derived rCBF, estimated by the ratio of tracer influx in target regions relative to reference region (R1) and early-stage PIB uptake (ePIB), to FDG scans. Fifteen PIB positive (+) patients and fifteen PIB negative (-) subjects underwent both FDG and PIB PET scans to assess the use of R1 and ePIB as a surrogate for FDG. First, subjects were classified based on visual inspection of the PIB PET images. Then, discriminative performance (PIB+ versus PIB-) of rCBF methods were compared to normalized regional FDG uptake. Strong positive correlations were found between analyses, suggesting that PIB-derived rCBF provides information that is closely related to what can be seen on FDG scans. Yet group related differences between method’s distributions were seen as well. Also, a better correlation with FDG was found for R1 than for ePIB. Further studies are needed to validate the use of R1 as an alternative for FDG studies in clinical applications.

Role of pretreatment fluorodeoxyglucose positron emission tomography quantitative parameters in prognostication of head-and-neck squamous cell carcinoma

Abstract In spite of the good organ preservation strategies available for locally advanced head-and-neck squamous cell carcinoma (HNSCC), failure rates have been reported to be as high as 35%–50%. There has been an increasing interest in predicting response to treatment, to aid early intervention and better outcomes. Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) is a standard modality for posttreatment evaluation; however, it is still underutilized as a pretreatment investigative modality. Several articles have described quantitative parameters in pretreatment FDG-PET to prognosticate patients and determine the likelihood of response to treatment; however, they are still not used commonly. This article was a review of the literature available on pretreatment FDG-PET quantitative parameters and their value in predicting failure. A thorough review of literature from MEDLINE and EMBASE was performed on pretreatment quantitative parameters in HNSCC. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were reliable parameters to predict response to organ preservation therapy, disease-free survival, and overall survival. Maximum SUV (SUVmax) was an inconsistent parameter. MTV and TLG may help predict poor response to organ preservation to initiate early surgical salvage or modify therapeutic decisions to optimize clinical outcomes. Routine use may provide additional information over SUVmax alone.

Multimodal PET/MRI Imaging Results Enable Monitoring the Side Effects of Radiation Therapy.

Radiotherapy is one of the most frequently applied treatments in oncology. Tissue-absorbed ionizing radiation damages not only targeted cells but the surrounding cells too. The consequent long-term induced oxidative stress, irreversible tissue damage, or second malignancies draw attention to the urgent need of a follow-up medical method by which personalized treatment could be attained and the actually dose-limiting organ could be monitored in the clinical practice. We worked out a special hemisphere irradiation technique for mice which mimics the radiation exposure during radiotherapy. We followed up the changes of possible brain imaging biomarkers of side effects, such as cerebral blood flow, vascular endothelial function, and cellular metabolic processes for 60 days. BALB/c mice were divided into two groups (n=6 per group) based on the irradiation doses (5 and 20 Gy). After the irradiation procedure arterial spin labeling (ASL), diffusion-weighted imaging (DWI) in magnetic resonance modality and [18F]fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) scans of the brain were obtained at several time points (3, 7, 30, and 60 days after the irradiation). Significant physiological changes were registered in the brain of animals following the irradiation by both applied doses. Elevated standard uptake values were detected all over the brain by FDG-PET studies 2 months after the irradiation. The apparent diffusion coefficients from DWI scans significantly decreased one month after the irradiation procedure, while ASL studies did not show any significant perfusion changes in the brain. Altogether, our sensitive multimodal imaging protocol seems to be an appropriate method for follow-up of the health status after radiation therapy. The presented approach makes possible parallel screening of healthy tissues and the effectiveness of tumor therapy without any additional radiation exposure.