18F-FDG Uptake Research Articles

Metabolic imaging in recurrent gliomas: comparative performance of 18F-FDOPA, 18F-fluorocholine and 18F-FDG PET/CT.

The aim of this study was to directly evaluate glucose, amino-acid and membrane metabolism in tumor cells for diagnosis and prognostication of recurrent gliomas. Fifty-five patients (median age = 36 years; 33 men) with histologically proven gliomas and suspected recurrence were prospectively recruited and underwent 18F-FDG (Fluorodeoxyglucose), 18F-FDOPA (fluorodopa) and 18F-Fluorocholine-PET/CT. Images were evaluated by two physicians visually and quantitatively [lesion-SUVmax, tumor (T) to gray-matter (G) and metabolically-active tumor volumes (MTV)]. After median follow-up of 51.5 months, recurrence was diagnosed in 49 patients. Thirty-one patients died with a median survival of 14 months. Diagnostic-accuracies for 18F-FDOPA, 18F-Fluorocholine,18F-FDG and contrast-enhanced-MRI were 92.7% (95% CI 82.7-97.1), 81.8% (69.7-89.8), 45.5% (33.0-58.5) and 44.7% (30.2-60.3), respectively. Among the 20 lesions, missed by MRI; 18F-FDOPA, 18F-Fluorocholine and 18F-FDG were able to detect 19, 14 and 4 lesions. Corresponding area-under-the-curves (T/G ratios) were 0.817 (0.615-1.000), 0.850 (0.736-0.963) and 0.814 (0.658-0.969), when differentiating recurrence from treatment-induced changes. In univariate-survival-analysis, 18F-FDOPA-T/G, visually detectable recurrence in 18F-FDG, 18F-FDOPA-MTV, cell-lineage and treatment-type were significant parameters. In Multivariate-Cox-regression analysis, 18F-FDOPA-MTV [HR = 1.009 (1.001-1.017); P = 0.024 (~0.9% increase in hazard for every mL increase of MTV)] and cell-lineage [3.578 (1.447-8.846); P = 0.006] remained significant. 18F-FDOPA-MTV cutoff <29.59 mL predicted survival higher than 2 years. At cutoff ≥29.59 mL, HR at 2 years was 2.759 (1.310-5.810). 18F-FDOPA-PET/CT can diagnose recurrence with high accuracy and MTV predicts survival. 18F-Fluorocholine is a good alternative. Higher 18F-FDG uptake is an adverse prognostic indicator.

Large PET/CT dataset statistics for the correlation between torso organ standardized uptake value and personal physiological features

ABSTRACT Background: The knowledge of [18F] fluoro-deoxy-glucose (18F-FDG) uptake range in normal torso organ is useful for metabolic disease diagnosis and treatment planning. This study aims to reveal the relationship between torso organ uptakes and personal physiological features, so as to quickly calculate the normal uptake value for patients according to his/her own physiological parameter. Materials and Methods: This study collected 767 18F-FDG positron emission tomography/computed tomography (PET/CT) images of normal people. The regions of torso organs were segmented and the mean values of classical body weight-normalized standard uptake value (W-SUV) and lean-body-mass-normalized standard uptake value (L-SUV) were calculated for each organ. The Pearson correlation coefficients and multiple regression formulas were calculated to reveal the influence of physiological features on W-SUV and L-SUV. Comparison between W-SUV and L-SUV were also conducted in terms of the correlation strength, regression confidence and inter-hospital consistency. Results: This study obtains the regression formulas for normal organ uptake calculation according to personal physiological parameters. The analysis reveals that lean body mass is the major factor affecting the uptakes of most organs (R &gt; 0.5). It is also worthy to find that the L-SUV formulas have better prediction confidence and inter-hospital consistency than the W-SUV, indicating the advantage of L-SUV for organ uptake evaluation. Conclusion: Compared to the previously similar studies, this study clarifies the influential factors of torso organ 18F-FDG uptake. We derived detailed formulas for computing individually adapted normal organ SUVs. The comparison between L-SUV and W-SUV also highlights the stability and reliability of L-SUV for cross-center organ uptake analysis.

Correlation between 18F-FDG PET-derived parameters and quantitative pathological characteristics of soft tissue sarcoma.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has been widely used for evaluating patients with soft tissue sarcoma (STS). However, uncertainties and overlap among individuals may be observed, and the relevance of these findings remains to be further explored. The present study was aimed at investigating the correlation between PET metabolic parameters and quantitative pathological characteristics in STS. We retrospectively collected 39 patients with STS who underwent 18F-FDG PET/computed tomography (CT) examination before treatment. Metabolic parameters including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and intratumoral FDG uptake heterogeneity (IFH) were measured. Histological grading was performed according to the French Federation of Cancer Centers grading system. Continuous staining of tissue sections and digital quantitative analysis methods were used, the characteristics of tumor nucleated cells were observed through hematoxylin-eosin staining, and the expression of CD163, CD68, CD8, and CD4 in tumor tissues was determined by immunohistochemistry (IHC), then the correlation between FDG metabolic parameters and the above quantitative pathological characteristics in patients with STS were evaluated. The SUVmax of 18F-FDG PET/CT in STS was positively correlated with the total nuclear area (r=0.355, P=0.027). SUVmax was also positively correlated with the expression levels of CD163, CD68, CD8, and CD4 (r=0.582, 0.485, 0.343, and 0.324, with P<0.001, 0.002, 0.032, and 0.044, respectively), but was not significantly correlated with cell count and mean nuclear area (all P>0.05). However, MTV, TLG, and IFH were not significantly correlated with the above quantitative pathological characteristics. Further multivariate logistic regression analysis indicated that only CD163 expression and histological grade were independently correlated with SUVmax. Moreover, SUVmax remained positively correlated with CD163 expression in the low-grade STS (r=0.820, P=0.001) and high-grade STS groups (r=0.430, P=0.028). 18F-FDG uptake was positively correlated with the quantitative pathological features of soft tissue tumors. SUVmax may be a meaningful method reflecting the level of M2 macrophage infiltration and may provide additional valuable information for preclinical evaluation of STS.

Right atrial wall inflammation detected by 18F-FDG PET/CT may be significantly associated with persistent atrial fibrillation: a prospective case-control study

AimAtrial fibrillation (AF) is a progressive disease from paroxysmal to persistent, and persistent AF (PerAF) had worse prognosis. AF has potential link with inflammation, but it is not clear whether PerAF or paroxysmal AF (ParAF) is more closely related to inflammation. On the basis of inhibiting myocardial physiological uptake, 18F-fluorodeoxyglucosepositron emission tomography/computed tomography (18F-FDG PET/CT) is an established imaging modality to detect cardiac inflammation. We aimed to decipher the association between AF and atrial inflammatory activity by 18F-FDG PET/CT.MethodsThirty-five PerAF patients were compared to age and sex matched ParAF group with baseline 18F-FDG PET/CT scans prior to radiofrequency catheter ablation (RFCA) in the prospective case-control study. High-fat and low-carbohydrate diet and prolonged fast (HFLC+Fast) was applied to all AF patients before PET/CT. Then 22 AF patients with positive right atrial (RA) wall FDG uptake (HFLC+Fast) were randomly selected and underwent HFLC+Fast+heparin the next day. The CHA2DS2-VASc score was calculated to evaluate the risk of stroke. Clinical data, ECG, echocardiography, and atrial 18F-FDG uptake were compared.ResultsPerAF patients had significantly higher probability of RA wall positive FDG uptake and higher SUVmax than ParAF group [91.4% VS. 28.6%, P < 0.001; SUVmax: 4.10(3.20–4.90) VS. 2.60(2.40–3.10), P < 0.001]. Multivariate logistic regression analyses demonstrated that RA wall SUVmax was the independent influencing factor of PerAF (OR = 1.80, 95%CI 1.02–3.18, P = 0.04). In 22 AF patients with RA wall positive FDG uptake (HFLC+Fast), the “HFLC+Fast+Heparin” method did not significantly change RA wall FDG uptake evaluated by either quantitative analysis or visual analysis. High CHA2DS2-VASc score group had higher RA wall 18F-FDG uptake [3.35 (2.70, 4.50) vs, 2.8 (2.4, 3.1) P = 0.01].ConclusionsRA wall FDG positive uptake was present mainly in PerAF. A higher RA wall 18F-FDG uptake was an independent influencing factor of PerAF. RA wall FDG uptake based on 18F-FDG PET/CT may indicate pathological inflammation.Trial registrationhttp://www.chictr.org.cn, ChiCTR2000038288.

The chicken chorioallantoic membrane as a low-cost, high-throughput model for cancer imaging

Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, and are constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice for preclinical cancer imaging studies. NCI-H460 FLuc cells grown in Matrigel on the CAM formed vascularized tumors of reproducible size without compromising embryo viability. By designing a simple method for vessel cannulation it was possible to perform dynamic PET imaging in ovo, producing high tumor-to-background signal for both 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) and (4S)-4-(3-18F-fluoropropyl)-L-glutamate (18F-FSPG). The pattern of 18F-FDG tumor uptake were similar in ovo and in vivo, although tumor-associated radioactivity was higher in the CAM-grown tumors over the 60 min imaging time course. Additionally, 18F-FSPG provided an early marker of both treatment response to external beam radiotherapy and target inhibition in ovo. Overall, the CAM provided a low-cost alternative to tumor xenograft mouse models which may broaden access to PET and SPECT imaging and have utility across multiple applications.

The Characterization of Metabolic Profile and Substrates Dependencies of Richter's Syndrome Cells Open for Translational Opportunities

Richter's syndrome (RS) is a high-grade aggressive lymphoma transformed from chronic lymphocytic leukemia (CLL), with a generally poor clinical outcome. The presence of sites of abnormally increased fluorodeoxyglucose F18 (18F-FDG) uptake on PET/CT of patients with CLL is predictive of Richter's transformation. The higher uptake of glucose in RS infiltrated lymph nodes compared to non-infiltrated ones together with evidence of metabolic reprogramming as a hallmark of cancer, prompt us to investigate the metabolic profile of RS cells and characterize their substrates dependencies. Exploiting 4 RS-patient-derived xenograft (PDX) models and the RS cell line U-RT1, we aimed to i) provide a complete picture of the metabolic landscape of RS cells, ii) identify the undeniable metabolites for these neoplastic cells, and iii) provide a proof-of-principle that metabolism can be a target for RS cells. Taking advantage of primary RS and CLL publicly available transcriptomic data, a clear shift in RNA expression was highlighted between the two disease phases, with an enrichment in metabolic processes-related terms within the upregulated genes. These results were validated in an internal cohort of primary RS samples and in the 4 RS-PDXs, with a complete overlap of the enriched “metabolic terms”, making these models representative tools to study the metabolic profile of RS cells. Specifically, gene sets enrichment analyses revealed oxidative phosphorylation, reactive oxygen species pathway, glycolysis, and fatty acid metabolism among the most significantly enriched gene sets in RS. This expression profile was supported by the measurement of the enzymatic activity of key enzymes belonging to glucose, glutamine, and fatty acid metabolic pathways. Three out of 4 PDXs and the U-RT1 cell line were characterized by an elevated metabolic rate compared to CLL, in terms of Krebs cycle, oxidative phosphorylation and glutamine metabolism, while the remaining RS-PDX model showed a more pronounced Warburg profile, with a stronger lactate dehydrogenase activity. These pathways are sustained by an increased glucose and glutamine uptake in RS cells leading to an elevated ATP content. Simultaneously, RS cells showed activation of anabolic processes that result in the synthesis of nucleotides and fatty acids. In line with these data, an unbiased approach based on metabolomic analyses identified a limited number of products of reaction, mainly attributable to pathways necessary both to produce energy and to provide building blocks (nucleotides, proteins and lipids) for cell proliferation. The metabolic dependencies of RS cells from glucose and glutamine were formally demonstrated by ex-vivo treatment with highly selective metabolic inhibitors. BPTES, a glutaminase inhibitor, and UK5099, a mitochondrial pyruvate carrier blocker, led to a significant decrease in the oxygen consumption rate and ATP production, while limited effects were observed when treating RS cells with Etomoxir, a fatty acid oxidation inhibitor. These reductions ultimately led to a significant induction of apoptosis in RS-PDXs derived cells. Finally, we showed that selective inhibitors of PI3K (duvelisib) and NF-kB (p65 inhibitor), two major regulators of energy metabolism and biosynthetic pathways, by interfering with the activity of these molecules, impacted on RS cells metabolism with a marked reduction of the oxidative phosphorylation and glycolytic cascade. Overall, these data depict the metabolic features of RS cells and their dependency from glucose and glutamine, at variance with CLL cells that mostly depend on fatty acid oxidation, thus suggesting a metabolic rewiring because of disease evolution. Moreover, they provide a proof-of-principle that metabolism can be envisaged as a candidate target for RS using either direct metabolic inhibitors or drugs that inhibit key metabolic regulators.

Assessment of treatment response in cardiac sarcoidosis based on myocardial 18F-FDG uptake.

Immunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of the heart. We conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020. We identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial 18F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed. TNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF.

Visualization of small brain nuclei with a high-spatial resolution, clinically available whole-body PET scanner

ObjectiveTo verify the visibility of physiological 18F-fluorodeoxyglucose (18F-FDG) uptake in nuclei in and around the brainstem by a whole-body (WB) silicon photomultiplier positron emission tomography (SiPM-PET) scanner with point-spread function (PSF) reconstruction using various iteration numbers.MethodsTen healthy subjects (5 men, 5 women; mean age, 56.0 ± 5.0 years) who underwent 18F-FDG PET/CT using a WB SiPM-PET scanner and magnetic resonance imaging (MRI) of the brain including a spin-echo three-dimensional sampling perfection with application-optimized contrasts using different flip angle evolutions fluid-attenuated inversion recovery (3D-FLAIR) and a 3D-T1 magnetization-prepared rapid gradient-echo (T1-MPRAGE) images were enrolled. Each acquired PET image was reconstructed using ordered-subset expectation maximization (OSEM) with iteration numbers of 4, 16, 64, and 256 (subset 5 fixed) + time-of-flight (TOF) + PSF. The reconstructed PET images and 3D-FLAIR images for each subject were registered to individual T1-MPRAGE volumes using normalized mutual information criteria. For each MR-coregistered individual PET image, the pattern of FDG uptake in the inferior olivary nuclei (ION), dentate nuclei (DN), midbrain raphe nuclei (MRN), inferior colliculi (IC), mammillary bodies (MB), red nuclei (RN), subthalamic nuclei (STN), lateral geniculate nuclei (LGN), medial geniculate nuclei (MGN), and superior colliculi (SC) was visually classified into the following three categories: good, clearly distinguishable FDG accumulation; fair, obscure contour of FDG accumulation; poor, FDG accumulation indistinguishable from surrounding uptake.ResultsAmong individual 18F-FDG PET images with OSEM iterations of 4, 16, 64, and 256 + TOF + PSF, the iteration numbers that showed the best visibility in each structure were as follows: ION, MRN, LGN, MGN, and SC, iteration 64; DN, iteration 16; IC, iterations 16, 64, and 256; MB, iterations 64 and 256; and RN and STN, iterations 16 and 64, respectively. Of the four iterations, the 18F-FDG PET image of iteration 64 visualized FDG accumulation in small structures in and around the brainstem most clearly (good, 98 structures; fair, 2 structures).ConclusionsA clinically available WB SiPM-PET scanner is useful for visualizing physiological FDG uptake in small brain nuclei, using a sufficiently high number of iterations for OSEM with TOF and PSF reconstructions.

PTPRH promotes the progression of non-small cell lung cancer via glycolysis mediated by the PI3K/AKT/mTOR signaling pathway

BackgroundThe protein tyrosine phosphatase H receptor (PTPRH) is known to regulate the occurrence and development of pancreatic and colorectal cancer. However, its association with glycolysis in non-small cell lung cancer (NSCLC) is still unclear. In this study, we aimed to investigate the relationship between PTPRH expression and glucose metabolism and the underlying mechanism of action.MethodsThe expression of PTPRH in NSCLC cells was evaluated by IHC staining, qRT‒PCR and Western blotting. The effect of PTPRH on cell biological behavior was evaluated by colony assays, EdU experiments, Transwell assays, wound healing assays and flow cytometry. Changes in F-18-fluorodeoxyglucose (18F‐FDG) uptake and glucose metabolite levels after altering PTPRH expression were detected via a gamma counter and lactic acid tests. The expression of glycolysis-related proteins in NSCLC cells was detected by Western blotting after altering PTPRH expression.ResultsThe results showed that PTPRH was highly expressed in clinical patient tissue samples and closely related to tumor diameter and clinical stage. In addition, PTPRH expression was associated with glycometabolism indexes on 18F-FDG positron emission tomography/computed tomography (PET/CT) imaging, the expression level of Ki67 and the expression levels of glycolysis-related proteins. PTPRH altered cell behavior, inhibited apoptosis, and promoted 18F-FDG uptake, lactate production, and the expression of glycolysis-related proteins. In addition, PTPRH modulated the glycometabolism of NSCLC cells via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, as assessed using LY294002 and 740Y-P (an inhibitor and agonist of PI3K, respectively). The same results were validated in vivo using a xenograft tumor model in nude mice. Protein expression levels of PTPRH, glycolysis-related proteins, p-PI3K/PI3K and p-AKT/AKT were measured by IHC staining using a subcutaneous xenograft model in nude mice.ConclusionsIn summary, we report that PTPRH promotes glycolysis, proliferation, migration, and invasion via the PI3K/AKT/mTOR signaling pathway in NSCLC and ultimately promotes tumor progression, which can be regulated by LY294002 and 740Y-P. These results suggest that PTPRH is a potential therapeutic target for NSCLC.Graphical

Arterial inflammation induced by immune checkpoint inhibitors assessed on 18F-FDG PET-CT scans in stage III/IV melanoma patients

Abstract Background In recent years, immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, as they lead to a substantial improvement in the prognosis of cancer patients. In high-grade melanoma patients, ICIs have doubled the three-year survival rate. However, ICIs may not only increase the immune response to tumor cells, but also to non-tumor cells, potentially inducing pro-atherogenic effects that can result in increased vascular inflammation and subsequent cardiovascular events. Purpose The objective of this study is to assess differences in vascular inflammation in the large arteries, as detected by 18F-FDG PET-CT scans, between stage III/IV melanoma patients receiving ICI therapy compared to stage III/IV melanoma patients not treated with ICIs. Methods The study population consisted of a cohort stage III/IV melanoma patients who underwent PET-CT scans at baseline, defined as &amp;lt; 1 year after diagnosis of stage III/IV melanoma and at T1 and T2, 6 months and 18 months after the baseline scan respectively. Patients with a history of cardiovascular events, treated with statins or corticosteroids (prednisolone &amp;gt; 10 mg per day) were excluded. Vascular inflammation was evaluated in the following eight arterial segments: the left and right carotid artery, ascending aorta, aortic arch, thoracic descending aorta, abdominal aorta and the left and right iliac artery. For each segment, the maximum standardized uptake value (SUV) for 18F-FDG uptake was derived and target-to-background ratio (TBR) was calculated from the ratio of the maximum SUV of the segment and the mean SUV of the superior and inferior vena cava. Vascular inflammation was defined as the total TBR per patient, calculated by sum of the TBR values of the eight arterial segments. The study endpoint was the difference in the increase in total TBR between patients treated with ICIs (exposure group) and patients without ICI treatment (control group). Results A total of 70 stage III/IV melanoma patients of whom 46 received ICIs and 24 did not receive ICI therapy were analyzed in this study. The median age at diagnosis was 61 years [IQR: 49-69] and 37 patients (52.9%) were female. The exposure group had a median ICI treatment of 9 [6-13] cycles. The results showed a significant difference in the TBR between the baseline PET-CT scan and T1 between the two groups. The control group showed a decrease in TBR by -0.33 [95% CI: -0.66 – 0.01], whereas the exposure group showed an increase in TBR by 0.17 [-0.14 – 0.49] (p = 0.045). No differences in TBR were found between T1 and T2. Conclusion The present study demonstrated that in stage III/IV melanoma patients treated with ICIs, there was a significant increase in vascular inflammation assessed by PET-CT in the large arteries during the first six months after treatment initiation, as compared to a control group without ICI treatment.∆TBR on PET-CT between baseline and T1∆TBR on PET-CT between T1 and T2

Abstract 17441: Non-Invasive Quantification of Peripheral Angioplasty-Induced Vascular Inflammation in a Porcine Model Using PET/CT Imaging

Background: Similarities in peripheral vascular anatomy between swine and humans make this animal an ideal model for evaluating the effects of lower extremity angioplasty procedures commonly performed to improve limb blood flow in peripheral artery disease (PAD). Hypothesis: We hypothesized that PET/CT imaging would provide a non-invasive strategy for quantifying the inflammatory response to balloon overdilation injury in a swine model of peripheral angioplasty. Methods: Five Yorkshire pigs (weight = 25 kg) underwent overdilation of the right femoral artery. A balloon catheter (7 mm x 40 mm) was introduced via the carotid artery and guided to the femoral artery under fluoroscopy. The balloon was then inflated to a pressure 1.5 times greater the recommended nominal pressure to induce arterial injury. 18 F-fluorodeoxyglucose (FDG) PET/CT imaging was performed 14 days after angioplasty to quantify in vivo inflammation in the injured and control femoral arteries, which was expressed as the maximum standardized uptake value (SUV max ). Pigs were euthanized 14 days post-angioplasty and arteries were harvested and sectioned for gamma counting ( 18 F-FDG uptake), and stained with hematoxylin and eosin histology (H&amp;E), Masson’s trichrome, and alpha-smooth muscle actin (α-SMA) for evaluation of intimal remodeling and smooth muscle cell proliferation. Results: 18 F-FDG PET/CT imaging quantified a significant increase in inflammation for the injured versus control femoral artery 14 days post-angioplasty (p=0.04). Gamma counting confirmed a significant increase in 18 F-FDG uptake in the injured artery (p=0.02). H&amp;E revealed a significant increase in intimal thickening in the injured artery (p=0.03). α-SMA expression was also significantly increased in the injured versus control femoral artery (p=0.01), demonstrating an increase in smooth muscle cell proliferation. Conclusions: 18 F-FDG PET/CT quantifies arterial inflammation resulting from overdilation injury that is associated with intimal remodeling and smooth muscle cell proliferation. PET/CT imaging may provide a non-invasive strategy for in vivo testing of the efficacy of emerging drug-coated endovascular peripheral devices.

Axillary Reverse Mapping in Clinically Node-Positive Breast Cancer Patients

Background: Axillary reverse mapping (ARM) nodes are involved in a significant proportion of clinically node-positive (cN+) breast cancer patients. However, neoadjuvant chemotherapy (NAC) is effective at decreasing the incidence of nodal metastases in cN+ patients. Patients and methods: One hundred forty-five cN+ patients with confirmed nodal involvement on ultrasound-guided fine needle aspiration cytology were enrolled in this study: one group underwent axillary lymph node dissection (ALND) without NAC (upfront surgery group), and the other group underwent ALND following NAC (NAC group). The patients underwent 18F-FDG-positron emission tomography/computed tomography (18F-FDG-PET/CT) before surgery, as well as an ARM procedure during ALND. Results: the rates of involvement of ARM nodes in the NAC group were significantly lower than those of the upfront surgery group (36.6% vs. 62.2%, p &lt; 0.01). Notably, involvement was significantly decreased after NAC in non-luminal-type tumors as compared to the luminal-type (18.4% vs. 48.5%: p &lt; 0.01). Moreover, there was a significant difference in ARM node involvement after NAC between patients with or without axillary uptake of 18F-FDG (61.5% vs. 32.5%: p &lt; 0.01). Conclusions: NAC significantly decreased the risk of ARM node metastases in cN+ patients, but 18F-FDG-PET/CT was not suitable to detect residual metastatic disease of the axilla after NAC.

PET Tracer-Based Glucose Uptake Predicts Clinical Response to Induction Therapy in Acute Myeloid Leukaemia

Metabolic re-programming enables cancer cells to harness various carbon substrates for energy production and biomass synthesis. Cell-intrinsic mechanisms of preferential glucose uptake is reported in acute myeloid leukaemia (AML). We previously identified leukaemia cells uptake more glucose compared with bone marrow micro-environment (BMME) cells in a MLL-AF9-driven AML mouse model (Leukemia 2023;37:1407). It is unknown how glucose is partitioned in the bone marrow, and whether glucose uptake variation correlates with response to induction chemotherapy in persons with newly-diagnosed AML. The radionuclide-labeled glucose analog 18F-2′-deoxy-2′-fluorodeoxyglucose ( 18F-FDG), a positron emission tomography (PET) probe, can be used to quantify in vivo glucose uptake in this setting. We studied this via a prospective pilot study (NCT05919199) in subjects with newly-diagnosed AML before receiving induction chemotherapy. Of 7 patients who have been enrolled in the study to date, all subjects were presented with various intensities of diffuse bone marrow 18F-FDG uptake in PET/CT images (maximum standardized uptake value (SUV max) mean, 6.0; range, 3.8-10.6). Subjects with higher SUV max in bone marrow had a higher likelihood of achieving a remission after induction therapy (Figure A). We use a 18F-FDG probe combined with magnetic-activated cell sorting (MACS) to quantify glucose uptake ( 18F radioactivity) in bulk and/or fractionated cell populations from subjects with AML at diagnosis. The associations between 18F-FDG uptake and response was better defined by per-cell glucose uptake quantification ( 18F counts per minute (CPM) per million cells) of bulk bone marrow cells. Higher 18F-FDG uptake correlated with a higher remission rate (Figure B). Notably, leukaemia cells from responders metabolized more glucose compared with micro-environment cells both of which had higher glucose uptake compared with non-responders. In contrast, leukaemia cells from non-responders had markedly decreased glucose uptake compared with micro-environment cells even they were sharing the same metabolic pool. These data indicate subject-specific glucose uptake is not directly affected by glucose availability but by cell-intrinsic glucose uptake programs. In light of data implicating mitochondrial metabolism in preserving leukaemia stem cells we speculated other energy sources such as amino acids and, fatty acids might compensate for decreased glucose uptake in non-responders. We utilized a computationally metabolic fluxome model, scFEA (Genome Res 2021;31:1867), which characterizes stochiometric relationships of metabolic networks and principal component analyses based on metabolism-related transcripts clustered samples by response. scFEA analysis of RNA-seq indicated responders had higher flux in the glucose import module, while flux of glutamine uptake were enriched in non-responders. These results suggest a switch from glucose (“Hot” AML) to glutamine metabolism (“Cold” AML) may protect leukaemia cells from chemotherapy stress. Taken together, we provide a rationale for in vivo evaluation of glucose uptake in AML patients, which is of potential use in discriminating patient response or resistance to induction therapies.

Comparison between an SGLT2 inhibitor and insulin in tumor-to-tissue contrasts in 18F-FDG PET imaging of diabetic mice

18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has been widely utilized for tumor diagnosis. Hyperglycemia affects the 18F-FDG uptake and reduces tumor-to-tissue contrasts, however, ideal hypoglycemic drugs are lacking. This study compared the role of insulin with the novel widely used hypoglycemic drug, sodium-glucose cotransporter 2 (SGLT2) inhibitor, on 18F-FDG PET imaging in diabetic conditions. The streptozotocin (STZ)-induced diabetic C57BL/6N mice were inoculated with B16 (mouse melanoma) cells to establish the xenograft tumor model. After the mice had been administrated with dapagliflozin (30 mg/kg, IG) or insulin (0.75 U/kg, IP) for one hour, 9.25 MBq/10 g 18F-FDG was injected. Biodistributions were detected by gamma counting and microPET imaging. The results showed dapagliflozin did not significantly affect the 18F-FDG uptake in tumors but reduced uptake in reference tissues, resulting in a significant increase in the tumor-to-skeletal muscle ratio. Conversely, insulin increased 18F-FDG uptake in tumors without significant reduction in uptake in reference tissues; Although there was an observable improvement in tumor imaging, it did not reach significantly statistical differences. This study suggests that insulin and SGLT2 inhibitor yield comparable effects on the quality of 18F-FDG PET imaging in diabetic patients. Nevertheless, SGLT2 inhibitors would be more suitable when skeletal muscle is used as reference tissue.

Increased Metabolic Activity of the Thymus and Lymph Nodes in Pediatric Oncology Patients After Coronavirus Disease 2019 Vaccination.

We hypothesized that 18F-FDG PET/MRI would reveal thymus activation in children after coronavirus disease 2019 (COVID-19) vaccination. Methods: We retrospectively analyzed the 18F-FDG PET/MRI scans of 6 children with extrathoracic cancer before and after COVID-19 vaccination. We compared pre- and postvaccination SUVmax, mean apparent diffusion coefficient, and size of the thymus and axillary lymph nodes using a paired t test. Results: All 6 patients showed increased 18F-FDG uptake in the axillary lymph nodes after vaccination (P = 0.03). In addition, these patients demonstrated increased 18F-FDG uptake in the thymus. When compared with baseline, the postvaccination scans of these patients demonstrated an increased mean thymic SUV (P = 0.02), increased thymic size (P = 0.13), and decreased thymic mean apparent diffusion coefficient (P = 0.08). Conclusion: 18F-FDG PET/MRI can reveal thymus activation in addition to local lymph node reactions in children after COVID-19 vaccination.

SARS-CoV-2 Affects Thyroid and Adrenal Glands: An 18F-FDG PET/CT Study.

Since most endocrine glands express ACE-2 receptors and can be infected by SARS-CoV-2 virus, this retrospective multicentre observational study aims to assess the metabolic activity of thyroid and adrenal glands of COVID-19 patients by 18F-FDG PET/CT. We retrospectively evaluated the 18F-FDG PET/CT scans of COVID-19 patients admitted by three different centres, either in a low-intensity department or in the intensive care unit (ICU). A visual assessment and a semi-quantitative evaluation of areas of interest in thyroid and adrenal glands were performed by recording SUVmax and SUVmean. The 18F-FDG PET/CT uptake in COVID-19 patients was compared with those observed in normal age-matched controls. Between March 2020 and March 2022, 33 patients from three different centres (twenty-eight patients in a low-intensity department and five patients in ICU), were studied by 18F-FDG PET/CT during active illness. Seven of them were also studied after clinical remission (3-6 months after disease onset). Thirty-six normal subjects were used as age-matched controls. In the thyroid gland, no statistically significant differences were observed between control subjects and COVID-19 patients at diagnosis. However, at the follow-up PET/CT study, we found a statistically higher SUVmax and SUVmean (p = 0.009 and p = 0.004, respectively) in the thyroid of COVID-19 patients. In adrenal glands, we observed lower SUVmax and SUVmean in COVID-19 patients at baseline compared to control subjects (p < 0.0001) and this finding did not normalize after clinical recovery (p = 0.0018 for SUVmax and p = 0.002 for SUV mean). In our series, we observed persistent low 18F-FDG uptake in adrenal glands of patients at diagnosis of COVID-19 and after recovery, suggesting a chronic hypofunction. By contrast, thyroid uptake was comparable to normal subjects at disease onset, but after recovery, a subgroup of patients showed an increased metabolism, thus possibly suggesting the onset of an inflammatory thyroiditis. Our results should alert clinicians to investigate the pituitary-adrenal axis and thyroid functionality at the time of infection and to monitor them after recovery.

68Ga-PSMA-11 PET/CT Imaging in Brain Gliomas and Its Correlation With Clinicopathological Prognostic Parameters.

Gliomas are the most common primary central nervous system tumors, of which the malignant gliomas account for 60%-75%. The primary and secondary brain malignancies are highly treatment resistant, and their marked angiogenesis attracts interest as a potential therapeutic target. The grade of gliomas, Ki-67 index, and IDH mutation status are among the major prognostic markers in gliomas. Prostate-specific membrane antigen (PSMA) is a zinc-dependent peptidase that is not only expressed in prostate cancer cells but also in the tumor neovasculature. The initial PSMA PET studies in central nervous system tumors using 68Ga-HBED-CC-PSMA (68Ga-PSMA-11) PET tracer confirmed selective target expression in gliomas of different grades, with higher expression in high-grade glioma compared with low-grade glioma. The aim of the present study was to correlate and compare the 68Ga-PSMA-11 and 18F-FDG uptake in brain tumors with their clinicopathological prognostic parameters, so as to study their prognostic implications. In addition, the study also aimed to identify patients who are likely to benefit from potential PSMA-targeted therapies. This ongoing prospective study was approved by the institutional scientific and medical ethics committee. The patients with primary or recurrent glioma lesions on MRI underwent regional brain PET/CT scanning with 68Ga-PSMA-11 and 18F-FDG. The final histopathology of the brain lesions (glioma grade), Ki-67 index, and IDH mutation status were compared with SUVmax values of the 68Ga-PSMA-11 and 18F-FDG PET/CT. A total of 15 patients (13 males and 2 females; age range, 21-73 years; median age, 58 years) were included in this study analysis. Among the 15 patients, 10 were treatment naive and 2 were patients with recurrent glioma. Three patients turned out to be WHO grade I-II, 6 belonged to grade III, and 6 grade IV (glioblastoma multiforme) on final histopathology. The 68Ga-PSMA-11 PET/CT showed tracer uptake in all high-grade gliomas with good tumor-to-background ratio. It was PSMA nonavid in 2/3 low-grade gliomas, and it showed low-grade uptake in 1/3 patients. PSMA expression (as evaluated by SUVmax values) was significantly higher in higher-grade tumors, those with IDH mutation wildtype status, and higher Ki-67 indices. FDG PET SUVmax also showed significant correlation with these prognostic parameters. In these preliminary results, PSMA PET appears to be an important tool in the evaluation and prognosis of gliomas. PSMA-directed theranostics can be explored as a personalized approach in gliomas with high PSMA uptake. However, with the limitation of small sample size, larger clinical trials are warranted to draw conclusive evidence regarding the same.

Simultaneous Uptake of 18F-NaF and 18F-FDG by Bladder and Prostate Calculi.

Calcification and formation of calculi in the genitourinary system such as the bladder, kidney, and prostate are common processes of aging. Despite being in different parts of the body, these calculi can share risk factors; for instance, bladder and prostate calculi are seen in older men with benign prostatic hyperplasia. There have been increasing reports of detection of calculi using PET tracers such as 18F-NaF and 18F-FDG, suggesting their role for detection of extraosseous calcification. In this report, we present simultaneous detection of bladder and prostate calculi with both 18F-NaF and 18F-FDG avidity in a 74-year-old man with multiple myeloma.

Physiologic 18F-FDG Uptake in Brown Adipose Tissue and Lactating Breast in a Patient with Hodgkin Lymphoma.

We present the case of a young woman with Hodgkin lymphoma exhibiting physiologic 18F-FDG uptake in brown adipose tissue and lactating breast on consecutive 18F-FDG PET/CT scans. Both entities are common imaging interpretation pitfalls and should be recognized in oncologic 18F-FDG PET/CT practice. We review the imaging features and differential diagnosis of these 2 entities and discuss the radiation safety precautions during breastfeeding.

The effect of hepatic steatosis on 18F-FDG uptake in PET-CT examinations of cancer Egyptian patients

BackgroundHepatic steatosis is the most common chronic hepatic disease. Imaging diagnosis of hepatic steatosis has been evaluated as an alternative to invasive histological diagnosis.Study aimsThe study aimed to assess the effect of hepatic steatosis on Flourine-18 fluorodeoxyglucose (18F-FDG) uptakes in cancer patients.Patients and MethodsBlood samples were collected from 50 cancer patients and analyzed to calculate fatty liver index and Hepatic steatosis index (HIS). Hepatic steatosis examined using high-resolution ultrasound and positron emission tomography—computed tomography (PET-CT). Linear attenuation coefficient, standardized-uptake value (SUV) mean (SUV mean), and SUV maximum (SUVmax) were measured. Accordingly, patients were divided equally into non-fatty liver, and fatty liver groups.ResultsA significant increase in SUVmax and SUV mean was observed in the fatty liver group more than in the non-fatty liver group. HSI significantly increased in the fatty liver group compared to the non-fatty liver group. Liver tissue uptake FDG was significantly correlated with HSI values. SUV max significantly correlated with body mass index (BMI) in the non-fatty group only.ConclusionHepatic changes in cancer patients affect the liver metabolic activity and thus the 18 F-FDG uptake. Therefore, further corrections should be considered when the liver is used as a comparator for PET-CT scans of cancer patients.