Differences In 18F-FDG Uptake Research Articles

Therapeutic Effect of Dupilumab on Systemic and Vascular Inflammation in Adults with Severe Atopic Dermatitis: Feasibility Study Using 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography

Atopic dermatitis (AD) is an inflammatory skin disease associated with increased systemic and vascular inflammation. Although dupilumab has been proven to be effective against severe AD, imaging studies analysing its inflammation-reducing effect have rarely been reported. The aim of this study was to evaluate the effect of dupilumab on systemic and vascular inflammation in adult patients with severe AD, using 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT). A total of 33 adult patients with severe AD and 25 healthy controls underwent 18F-FDG PET/CT at baseline. Patients on dupilumab treatment underwent 18F-FDG PET/CT again after achieving a 75% reduction from baseline on the Eczema Area and Severity Index (EASI-75). Patients with AD exhibited increased 18F-FDG uptake values in the liver, spleen, pancreas, and carotid artery compared with healthy controls. However, compared with baseline, there was no statistically significant difference in 18F-FDG uptake in major organs and arteries after achieving EASI-75 with dupilumab treatment. In conclusion, while dupilumab treatment resulted in a significant clinical improvement and reduced serum inflammatory markers in adult patients with severe AD, no changes in systemic and vascular inflammation were observed on 18F-FDG PET/CT imaging.

Glucose-Thymidine Ratio as a Metabolism Index Using 18F-FDG and 18F-FLT PET Uptake as a Potential Imaging Biomarker for Evaluating Immune Checkpoint Inhibitor Therapy.

Immune checkpoint inhibitors (ICIs) are widely used in cancer immunotherapy, requiring effective methods for response monitoring. This study evaluated changes in 18F-2-fluoro-2-deoxy-D-glucose (FDG) and 18F-fluorothymidine (FLT) uptake by tumors following ICI treatment as potential imaging biomarkers in mice. Tumor uptakes of 18F-FDG and 18F-FLT were measured and compared between the ICI treatment and control groups. A combined imaging index of glucose–thymidine uptake ratio (GTR) was defined and compared between groups. In the ICI treatment group, tumor growth was effectively inhibited, and higher proportions of immune cells were observed. In the early phase, 18F-FDG uptake was higher in the treatment group, whereas 18F-FLT uptake was not different. There was no difference in 18F-FDG uptake between the two groups in the late phase. However, 18F-FLT uptake of the control group was markedly increased compared with the ICI treatment group. GTR was consistently higher in the ICI treatment group in the early and late phases. After ICI treatment, changes in tumor cell proliferation were observed with 18F-FLT, whereas 18F-FDG showed altered metabolism in both tumor and immune cells. A combination of 18F-FLT and 18F-FDG PET, such as GTR, is expected to serve as a potentially effective imaging biomarker for monitoring ICI treatment.

Differentiation of acute myeloid leukemia (AML) cells with ATRA reduces 18F-FDG uptake and increases sensitivity towards ABT-737-induced apoptosis

Acute myeloid leukemia (AML) is a malignant disease of the bone marrow, comprising various subtypes. We have investigated seven different AML cell lines that showed different sensitivities toward the inducer of apoptosis ABT-737, with IC50 concentrations ranging from 9.9 nM to 1.8 µM. Besides, the AML cell lines revealed distinct differences in 18F-FDG uptake ranging from 4.1 to 11.0%. Moreover, the Pearson coefficient (0.363) suggests a moderate correlation between 18F-FDG uptake and the IC50 values of ABT-737. Differentiation of the AML cell lines NB-4 and AML-193 with all-trans-retinoic-acid (ATRA) induced a significant increase in sensitivity towards ABT-737 along with a reduced uptake of 18F-FDG. Therefore, 18F-FDG uptake could be predictive on sensitivity to treatment with ABT-737. Furthermore, because differentiation treatment of AML cells using ATRA reduced 18F-FDG uptake and increased sensitivity towards ABT-737, a combined treatment regimen with ATRA and ABT-737 might be a promising therapeutic option in the future.

Relationship between SP142 PD-L1 Expression and 18F-FDG Uptake in Non-Small-Cell Lung Cancer.

Objectives Immune checkpoint blockers constitute the first-line treatment for advanced non-small-cell lung cancer (NSCLC) with ≥50% PD-L1 expression. In NSCLC, PD-L1 positivity is correlated with high 18F-fluorodeoxyglucose (18F-FDG) uptake. However, these studies only included patients undergoing surgical resection, almost all in their early stages. Moreover, differences in 18F-FDG uptake between NSCLC with high (≥50%) and low (49%) PD-L1 expression remain unknown. We aimed to investigate the association between metabolic parameter 18F-FDG uptake and PD-L1 expression status in NSCLC patients. Methods From February 2017 to June 2018, 428 consecutive NSCLC patients who underwent 18F-FDG positron emission tomography/computed tomography (PET/CT) and SP142 PD-L1 expression analysis were retrospectively assessed. The association between clinicopathological characteristics and PD-L1 expression was examined. Results The frequency of PD-L1-positive tumors was 38.1% (163/428), 28.5% (91/319), and 64.2% (61/95) for NSCLC, adenocarcinoma (ADC), and squamous cell carcinoma (SCC), respectively. Maximal standard uptake (SUVmax) was significantly higher in PD-L1-positive than in PD-L1-negative NSCLC (p < 0.0001), ADC (p < 0.0001), and SCC (p=0.006). SUVmax was significantly higher in NSCLC (p=0.001) and ADC (p=0.003) with high rather than low PD-L1 expression. The receiver operating characteristic curve yielded area under the curve values of 0.726 (95% CI, 0.679–0.774, p < 0.0001), 0.694 (95% CI, 0.634–0.755, p < 0.0001), and 0.625 (95% CI, 0.513–0.738, p=0.044) for NSCLC, ADC, and SCC, respectively. Conclusion 18F-FDG tumor uptake is strongly, positively correlated with PD-L1 expression in NSCLC and significantly differs between high and low PD-L1-expressing individuals.

Combined PET/CT with thoracic contrast-enhanced CT in assessment of primary cardiac tumors in adult patients

Background18F-FDG PET/CT is a key molecular imaging modality to noninvasively assess and differentiate benign and malignant cardiac tumors. However, few benign cardiac tumors can be characterized by increased 18F-FDG uptake, which makes differential diagnosis difficult. This study sought to retrospectively evaluate whether combined 18F-FDG PET/CT with thoracic contrast-enhanced CT (CECT) helps in assessing primary cardiac tumors in adult patients, compared with CECT or PET/CT alone.MethodsForty-six consecutive patients who were diagnosed as primary cardiac tumors were enrolled. All patients underwent 18F-FDG PET/CT followed by thoracic CECT before biopsy or surgery. Visual qualitative interpretation and quantitative analysis were performed, and diagnostic performance was evaluated.ResultsMore than half (16/29) of benign tumors exhibited with mild 18F-FDG uptake. There were significant differences in 18F-FDG uptake and the degree of absolute enhancement between benign and malignant tumors (P < 0.001). The combination of two modalities improved the specificity from 79 to 93%, the positive predictive value from 73 to 89%, and the accuracy of diagnosis from 85 to 93%. There were significant differences between PET/CT alone or thoracic CECT alone and combined modalities (P = 0.034 and P = 0.026, respectively). The combination with the optimal SUVmax cutoff value generated 94% sensitivity, 100% specificity, 97% negative predictive values, 100% positive predictive values, and 98% accuracy rates.ConclusionsCombining 18F-FDG PET/C with thoracic CECT significantly improved specificity and accuracy compared to CECT or PET/CT alone in detecting tumors. This combination of diagnostic imaging is effective in differentiating malignant from benign masses.

Usefulness of [18F]fluorodeoxyglucose PET/CT for evaluating the PD-L1 status in nasopharyngeal carcinoma.

To explore the relationship between [18F]fluorodeoxyglucose (18F-FDG uptake) and PD-L1 expression and determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in tumour cells (TCs) and tumour-infiltrating immune cells (TIICs) in patients with nasopharyngeal carcinoma (NPC). We retrospectively evaluated the records of 84 eligible patients who received an initial histopathological diagnosis of NPC between December 2016 and March 2019. All tissue specimens and PET/CT images were collected prior to treatment. High PD-L1 expression in TCs and TIICs was defined as ≥ 50% of stained cells. There was a significant difference in 18F-FDG uptake according to the PD-L1 status in TCs and TIICs. Univariate analysis showed that PD-L1 expression in TCs was associated with tumour maximum standardized uptake value (SUVmax) (P < 0.001), primary tumour total lesion glycolysis (TLG; P < 0.001), and T stage (P = 0.044), but not with plasma Epstein-Barr virus (EBV) load (P = 0.816), whereas PD-L1 expression in TIICs was related to SUVmax (P = 0.011), TLG (P = 0.001), T stage (P = 0.028), and plasma EBV load (P = 0.003). In multivariate logistic regression, PD-L1 expression in TCs was positively associated with SUVmax (P = 0.003) and TLG (P = 0.001), and in TIICs, negatively associated with SUVmax (P = 0.038) and plasma EBV load (P = 0.025). 18F-FDG uptake in NPC lesions was positively correlated with PD-L1 expression in TCs and negatively correlated with PD-L1 expression in TIICs. Thus, 18F-FDG PET/CT may be useful for evaluating the PD-L1 status in patients with NPC.

Using of ¹⁸F-FDG to evaluate the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway: a PET-MRI pilot study

Objective:This study evaluated the effect of traumatic olfactory nerve injury on drug delivery through the nasal-brain pathway via the instillation of ¹⁸F-FDG at the olfactory cleft. Method:Seven healthy volunteers and 5 patients with traumatic dysosmia were enrolled in the study. Subjects were all instilled with ¹⁸F-FDG on each side of the olfactory cleft under endoscopy. After 12 hours, a PET/MR scan was performed to track the metabolism pathway of ¹⁸F-FDG. Then, we compared the diameter of the olfactory bulb and the olfactory bulb intake between normal volunteers and patients with traumatic olfactory disorders. Result:In healthy volunteers, there was a significant difference in ¹⁸F-FDG uptake between the regions of interest in which ¹⁸F-FDG was or was not in contact with the cribriform plate（P=0.012 7）; this difference also existed in patients with traumatic olfactory disorders（P=0.038 1）. Patients with traumatic olfactory disorders did not exhibit significant differences in ¹⁸F-FDG uptake in the region of interest compared with healthy volunteers（P=0.937 2）. Conclusion:The olfactory bulb is obviously atrophied in patients with traumatic olfactory dysfunction, and the uptake of ¹⁸F-FDG in the olfactory bulb region of interest is also reduced. The administration of ¹⁸F-FDG via olfactory fissure area can enter olfactory bulb and parafrontal tissues through the nasal brain pathway,¹⁸F-FDG can enter the central nervous system through the nasal-brain pathway, which is not affected by olfactory nerve transection injury.

CBMT-03. EVALUATION OF PET TRACERS TO DIFFERENTIATE IDH1 MUTANT GBM

Abstract OBJECTIVE PET/CT offers the unique potential to noninvasively evaluate biomarker expression and aberrant metabolism. 18F-FDG has driven PET/CT to the forefront of cancer imaging, as altered glucose metabolism is a hallmark of oncogenesis. However, 18F-FDG is suboptimal for GBM due to high physiologic uptake in normal brain. The development of alternative tracers has reignited the field of PET/CT in GBM and offers hope for diagnosis and molecular staging in GBM. We hypothesize that fundamental differences in metabolism and oncogene expression present in IDH1 mutatant gliomas can be shown using PET imaging, as has been suggested in some correlative clinical studies. Our objective was therefore to establish a causal link between IDH1 mutation in GBM and uptake of targeted PET tracers in a unique proneural GBM transgenic model characterized by p53, IDH1 mutations and PDGF expression. METHODS We examined the uptake of 3 blood-brain-barrier (BBB) penetrant tracers that have been used in GBM: (a) 18F-FDG, a surrogate for increased glycolysis; (b) 18F-Fluciclovine, an amino acid derivative transported into cells through the energy-independent L-type amino acid transporter (LAT) system and is approved by the FDA for prostate cancer; and (c) 11C-ER176, a tracer that binds the TSPO receptor that is generally expressed on activated microglia as well as GBM. RESULTS We did not observe significant differences in 18F-FDG uptake between wt and IDH mutant GBM cells. However, we found that IDH mutant GBM cells demonstrated significantly increased 18F-Fluciclovine (47%) and 11C-ER176 (53%) versus IDH wt cells. CONCLUSION We have established a causal link between IDH mutation status and uptake of (a) 18F-Fluciclovine, a promising FDA approved PET tracer and (b) 11C-ER176, a second generation TSPO ligand. Thus, we are performing further studies in orthotopic syngeneic GBM models to determine if PET imaging can non-invasively demonstrate molecular characterization and therapeutic stratification in glioma.

Monitoring Src status after dasatinib treatment in HER2+ breast cancer with 89Zr-trastuzumab PET imaging

BackgroundDe novo or acquired resistance in breast cancer leads to treatment failures and disease progression. In human epidermal growth factor receptor 2 (HER2)-positive (HER2+) breast cancer, Src, a non-receptor tyrosine kinase, is identified as a major mechanism of trastuzumab resistance, with its activation stabilizing aberrant HER2 signaling, thus making it an attractive target for inhibition. Here, we explored the causal relationship between Src and HER2 by examining the potential of 89Zr-trastuzumab as a surrogate imaging marker of Src activity upon inhibition with dasatinib in HER2+ breast cancer.MethodsHER2+ primary breast cancer cell lines BT-474 and trastuzumab-resistant JIMT-1 were treated with dasatinib and assessed for expression and localization of HER2, Src, and phosphorylated Src (pSrc) (Y416) through western blots and binding assays. Mice bearing BT-474 or JIMT-1 tumors were treated for 7 or 14 days with dasatinib. At the end of each treatment, tumors were imaged with 89Zr-trastuzumab. The results of 89Zr-trastuzumab positron emission tomography (PET) was compared against tumor uptake of fluorodeoxyglucose (18F-FDG) obtained the day before in the same group of mice. Ex vivo western blots and immunohistochemical staining (IHC) were performed for validation.ResultsIn BT-474 and JIMT-1 cells, treatment with dasatinib resulted in a decrease in internalized 89Zr-trastuzumab. Confirmation with immunoblots displayed abrogation of pSrc (Y416) signaling; binding assays in both cell lines demonstrated a decrease in cell surface and internalized HER2-bound tracer. In xenograft models, dasatinib treatment for 7 days (BT-474, 11.05 ± 2.10 % injected dose per gram of tissue %(ID)/g; JIMT-1, 3.88 ± 1.47 %ID/g)) or 14 days (BT-474, 9.20 ± 1.85 %ID/g; JIMT-1, 4.45 ± 1.23 %ID/g) resulted in a significant decrease in 89Zr-trastuzumab uptake on PET compared to untreated control (BT-474, 17.88 ± 2.18 %ID/g; JIMT-1, 8.04 ± 1.47 %ID/g). No difference in 18F-FDG uptake was observed between control and treated cohorts. A parallel decrease in membranous HER2 and pSrc (Y416) staining was observed in tumors post treatment on IHC. Immunoblots further validated the 89Zr-trastuzumab-PET readout. Positive correlation was established between 89Zr-trastuzumab tumor uptake versus tumor regression, pSrc and pHER2 expression.Conclusions89Zr-trastuzumab can potentially assess tumor response to dasatinib in HER2+ breast cancer and could be used as a surrogate tool to monitor early changes in Src signaling downstream of HER2.

Regional Changes in Brain 18F-FDG Uptake After Prophylactic Cranial Irradiation and Chemotherapy in Small Cell Lung Cancer May Reflect Functional Changes.

Chemotherapy followed by prophylactic cranial irradiation (PCI) is associated with increased survival in patients with small cell lung cancer but is associated with fatigue and cognitive impairment. This retrospective study evaluated regional differences in 18F-FDG uptake by the brain before and after PCI. The null hypothesis was that direct toxic effects on the brain from PCI and chemotherapy are symmetric; thus, asymmetric deviations may reflect functional changes due to therapy. Methods: Electronic medical records from 2013 to 2016 were reviewed for patients with small cell lung cancer, MRI of brain negative for metastasis, and 18F-FDG PET/CT scans before and after PCI. As the standard of care, patients received first-line chemotherapy or chemoradiation to the thorax followed by PCI. The 18F-FDG PET/CT scans nearest the PCI were selected. Sixteen patients met these initial criteria. Commercially available PET software was used to register and subtract the PET scans before and after PCI to obtain difference maps. Occipital and cerebellar regions were excluded from the final statistical analysis given the known high variability and misregistration. The χ2 test was used to analyze the data. Results: Two patients had 18F-FDG uptake differences only in the occipital and cerebellar regions. The software registration failed on 1 patient's scans. Therefore, 13 patients were included in the final analysis. Nine of 13 patients demonstrated significant unilateral changes in only 1 region of the brain, and 3 of 13 showed significant changes unilaterally in 2 regions. The χ2 test revealed a significant unilateral regional difference on a patient level (χ2 = 6.24, P = 0.025). The most commonly affected brain region was the frontal lobe. Conclusion: Significantly more patients had unilateral than bilateral regional differences (both increases and decreases) in 18F-FDG uptake in the brain before and after PCI. This finding suggests that differences in unilateral distribution are related to functional changes, since direct toxicity alone from PCI and chemotherapy would be symmetric. The frontal region was the most commonly affected, suggesting a potential contributing etiology for cognitive impairment and decreased executive function after therapy.

Bone marrow mesenchymal stem cell transplantation in acute brain trauma

SummaryAim: This study was performed to evaluate the effects of intravenously transplanted rat bone-marrow derived mesenchymal stem cells (rBMSCs) in an acute brain trauma model using serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in rat models. Animals, methods: Trauma models were made using a controlled cortical impact injury device. The stem cell treatment group was treated with intravenous injections of BMSCs, and models without stem cell therapy comprised the control group. Serial 18F-FDG PET images were obtained 1, 7, 14, 21, and 28 days after trauma. The difference in 18F-FDG uptake between day 1 and each time point after trauma was analyzed with SPM2 (uncorrected p &lt; 0.005). Results: The stem cell treatment group demonstrated significantly higher 18F-FDG uptake in the right parietal region at 14 days after trauma than at 1 day after trauma. An increase in glucose metabolism in the right parietal cortex appeared on days 21 and 28 after trauma in the group without stem cell treatment. The 18F-FDG uptake in the brain was improved over a broader area, including the right parietal and right primary somatosensory cortex, on days 21 and 28 after trauma in the stem cell treatment group compared with the group without stem cell treatment. Conclusion: BMSC therapy in trauma models led to improved glucose metabolism. This result might support the therapeutic effect of stem cells in brain trauma.

Role of 18F-FDG-PET/CT in the assessment of carotid atherosclerosis

The aim of this study was to determine the role of 18F-FDG-PET/CT in the evaluation of carotid plaques and its relationship with cardiovascular risk factors. 18F-FDG-PET/CT scan was performed in 25 patients with ultrasound diagnosis of carotid atherosclerosis and ≥70% stenosis, who were scheduled for carotid endoarterectomy. 18F-FDG uptake was measured by ROIs drawn on PET/CT carotid artery slices. A statistically significant difference in 18F-FDG uptake was observed in relation to body mass index values between 25 and 29 kg/m2. Our results suggest that PET/CT imaging has utility in risk stratification of atherosclerotic patients.