• Korean Journal of Radiology
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• v.23 no.9
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• pp.921-930
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• 2022

Objective: To identify epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma based on ¹⁸F-fluorodeoxyglucose (FDG) PET/CT radiomics and clinical features and to distinguish EGFR exon 19 deletion (19 del) and exon 21 L858R missense (21 L858R) mutations using FDG PET/CT radiomics. Materials and Methods: We retrospectively analyzed 179 patients with lung adenocarcinoma. They were randomly assigned to training (n = 125) and testing (n = 54) cohorts in a 7:3 ratio. A total of 2632 radiomics features were extracted from the tumor region of interest from the PET (1316) and CT (1316) images. Six PET/CT radiomics features that remained after the feature selection step were used to calculate the radiomics model score (rad-score). Subsequently, a combined clinical and radiomics model was constructed based on sex, smoking history, tumor diameter, and rad-score. The performance of the combined model in identifying EGFR mutations was assessed using a receiver operating characteristic (ROC) curve. Furthermore, in a subsample of 99 patients, a PET/CT radiomics model for distinguishing 19 del and 21 L858R EGFR mutational subtypes was established, and its performance was evaluated. Results: The area under the ROC curve (AUROC) and accuracy of the combined clinical and PET/CT radiomics models were 0.882 and 81.6%, respectively, in the training cohort and 0.837 and 74.1%, respectively, in the testing cohort. The AUROC and accuracy of the radiomics model for distinguishing between 19 del and 21 L858R EGFR mutational subtypes were 0.708 and 66.7%, respectively, in the training cohort and 0.652 and 56.7%, respectively, in the testing cohort. Conclusion: The combined clinical and PET/CT radiomics model could identify the EGFR mutational status in lung adenocarcinoma with moderate accuracy. However, distinguishing between EGFR 19 del and 21 L858R mutational subtypes was more challenging using PET/CT radiomics.

• The Korean Journal of Nuclear Medicine
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• v.31 no.3
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• pp.381-387
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• 1997

Cancer tissues are characterized by increased glucose uptake. $^{18}F$-fluorodeoxyglucose(FDG), a glucose analogue is used for the diagnosis of cancer in PET studies. This study was aimed to compare the glucose uptake and glucose transporter 1(GLUT1) expression in various human colon cancer cells. We measured FDG uptake by cell retention study and expression of GLUT1 using Western blotting. Human colon cancer cells, SNU-C2A, SNU-C4 and SNU-C5, were used. The cells were incubated with $1{\mu}Ci/ml$ of FDG in HEPES-buffered saline for one hour. The FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were $16.8{\pm}1.36,\;12.3{\pm}5.55$ and $61.0{\pm}2.17cpm/{\mu}g$ of protein, respectively. Dose-response and time-course studies represent that FDG uptake of cancer cells were dose dependent and time dependent. The rate of FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were $0.29{\pm}0.03,\;0.21{\pm}0.09$ and $1.07{\pm}0.07cpm/min/{\mu}g$ of protein, respectively. Western blot analysis showed that the GLUT1 expression of SNU-C5 was significantly higher than those of SNU-C2A and SNU-C4. These results represent that FDG uptake into human colon cancer cells are different from each other. In addition, FDG uptake and expression of GLUT1 are closely related in human colon cancer cells.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.384-393
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• 2017

Purpose: The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-($^{18}F$)fluoro-D-glucose ($^{18}F-FDG$) positron emission tomography (PET)-computed tomography (CT) ($^{18}F-FDG$ PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods: We retrospectively reviewed 56 patients who underwent $^{18}F-FDG$ PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: ($10{\times}serum$ albumin value)+($0.005{\times}peripheral$ lymphocyte counts). Additionally, the maximum standard uptake value ($SUV_{max}$) was calculated to evaluate the metabolic activity of cancer cells. Results: The $SUV_{max}$ was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=-0.407; P=0.002). A higher $SUV_{max}$ showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with $SUV_{max}$ or TILs. Survival analysis, however, indicated that neither $SUV_{max}$ nor Foxp3 held prognostic significance. Conclusions: FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.

• The Journal of the Korean bone and joint tumor society
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• v.14 no.1
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• pp.44-50
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• 2008

Purpose: To evaluate usefulness in diagnosing primary malignant lesion of metastatic bone tumor using $^{18}F$ FDG PET/CT. Material & Methods: Retrospective analysis was executed on 5,452 patients who were taken with $^{18}F$ FDG PET/CT between December 2003 and December 2007. 180 patients who had not any history of malignancy and complained musculoskeletal pain and had ill-defined osteolytic lesion in plain X-ray, were included. 96 male and 84 female were enrolled and mean age was 59.1 year old (22~90). We analyzed diagnostic accuracy, age and sex distribution of primary malignant lesion, location of metastatic lesion. Results: We could confirmed primary malignant lesion in 152 cases (84.4%). Most common malignant primary lesion was lung (28.3%), breast (18.9%) and gastrointestinal system (16.7%) and spine was the most common metastatic location of primary malignant lesion. Conclusion: $^{18}F$ FDG PET/CT is a effective molecular imaging detecting primary malignant lesion in patients having metastatic bone lesion without history of malignancy.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.6
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• pp.535-542
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• 2009

Purpose: This study was performed to know whether [$^{18}F$]Fluorothymidine (FLT) positron emission tomography (PET) can be used to monitor early response to radiotherapy in comparison with [$^{18}F$]Fluorodeoxyglucose (FDG) PET, and to establish the optimal imaging time for prediction of therapy response. Materials and Methods: Two patients with nasopharyngeal cancer underwent serial FLT PET and FDG PET before and during radiotherapy. Three on-treatment FLT and FDG PET scans were performed on 1 week, 2 weeks and 3 weeks (at each time of 10 Gy, 20 Gy and 30 Gy delivered). The peak standardized uptake values ($SUV_{peak}$) of primary tumors were measured on FLT and FDG PET. Then, percent changes of $SUV_{peak}$ after therapy were calculated. Results: In two patients, baseline values of $SUV_{peak}$ on FDT PET were higher than those on FLT PET (FLT vs FDG; 3.7 vs 5.0, and 5.7 vs 15.0). In patient 1, FLT $SUV_{peak}$ showed 78%, 78% and 84% of decrease on 1 week, 2 and 3 weeks after treatment, whereas FDG $SUV_{peak}$ showed 18%, 52% and 66% of decrease, respectively. In patient 2, FLT $SUV_{peak}$ showed 75%, 75% and 68% of decrease, whereas FDG $SUV_{peak}$ showed 51%, 49% and 58% of decrease, respectively. Both patients reached to complete remission after radiotherapy. Conclusion: After radiotherapy, the decrease of FLT tumor uptake preceded the decrease of FDG tumor uptake in patients with nasopharyngeal cancer, and 1 week after therapy may be appropriate time for the assessment of early response. FLT PET might be more useful than FDG PET for monitoring early response to radiotherapy.

• The Korean Journal of Nuclear Medicine
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• v.37 no.5
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• pp.331-335
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• 2003

Purpose: Accurate assessment of the lesion after treatment of patients with bone lymphoma is difficult. In this patient who demonstrated complete remission after chemotherapy, the regions of fluorine-18 fluorodeoxyglucose $(^{18}FFDG)PET$ uptake diminished more rapidly fellowing therapy, indicating a complete response at much earlier stage than did Magnetic Resonance Imaging (MRI) or CT based findings. With the conventional methods, such as MRI and CT, It was difficult to assess whether the residual tumor tissue was viable or not. Decision to complete response is very important in patients with lymphoma to plan the further treatment. We experienced a patient with primary lymphoma of bone who revealed complete response to chemotherapy on $^{18}FFDGPET$ while CT showed persistent destructive bone lesion. Thus, $^{18}FFDGPET$ study after therapy may be superior to CT in the evaluation of response to treatment in primary lymphoma of bone.

• Radiation Oncology Journal
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• v.29 no.3
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• pp.214-217
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• 2011

To avoid improper tumor volume contouring in radiation therapy (RT) and other invasive procedures, we report a case of uterine adenomyosis showing increased $^{18}F$-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT) mimicking malignant tumor in a 44-year-old woman during concurrent chemoradiation therapy (CCRT) for uterine cervical cancer. The adenomyosis was not associated with her menstrual cycle or with normal endometrium uptake, and it resolved one month after completion of RT. This case indicates that uterine adenomyosis in a premenopausal woman may show false positive uptake of $^{18}FDG$-PET/CT associated with CCRT.

• Brain Tumor Research and Treatment
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• v.6 no.2
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• pp.47-53
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• 2018

Brain tumors represent a diverse spectrum of histology, biology, prognosis, and treatment options. Although MRI remains the gold standard for morphological tumor characterization, positron emission tomography (PET) can play a critical role in evaluating disease status. This article focuses on the use of PET with radiolabeled glucose and amino acid analogs to aid in the diagnosis of tumors and differentiate between recurrent tumors and radiation necrosis. The most widely used tracer is $^{18}F$-fluorodeoxyglucose (FDG). Although the intensity of FDG uptake is clearly associated with tumor grade, the exact role of FDG PET imaging remains debatable. Additionally, high uptake of FDG in normal grey matter limits its use in some low-grade tumors that may not be visualized. Because of their potential to overcome the limitation of FDG PET of brain tumors, $^{11}C$-methionine and $^{18}F$-3,4-dihydroxyphenylalanine (FDOPA) have been proposed. Low accumulation of amino acid tracers in normal brains allows the detection of low-grade gliomas and facilitates more precise tumor delineation. These amino acid tracers have higher sensitivity and specificity for detecting brain tumors and differentiating recurrent tumors from post-therapeutic changes. FDG and amino acid tracers may be complementary, and both may be required for assessment of an individual patient. Additional tracers for brain tumor imaging are currently under development. Combinations of different tracers might provide more in-depth information about tumor characteristics, and current limitations may thus be overcome in the near future. PET with various tracers including FDG, $^{11}C$-methionine, and FDOPA has improved the management of patients with brain tumors. To evaluate the exact value of PET, however, additional prospective large sample studies are needed.

• Korean Journal of Radiology
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• v.23 no.4
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• pp.466-478
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• 2022

Objective: ¹⁸F-fluorodeoxyglucose (FDG) PET/CT is often used for detecting malignancy in patients with newly diagnosed hemophagocytic lymphohistiocytosis (HLH), with acceptable sensitivity but relatively low specificity. The aim of this study was to improve the diagnostic ability of ¹⁸F-FDG PET/CT in identifying malignancy in patients with HLH by combining ¹⁸F-FDG PET/CT and clinical parameters. Materials and Methods: Ninety-seven patients (age ≥ 14 years) with secondary HLH were retrospectively reviewed and divided into the derivation (n = 71) and validation (n = 26) cohorts according to admission time. In the derivation cohort, 22 patients had malignancy-associated HLH (M-HLH) and 49 patients had non-malignancy-associated HLH (NM-HLH). Data on pretreatment ¹⁸F-FDG PET/CT and laboratory results were collected. The variables were analyzed using the Mann-Whitney U test or Pearson's chi-square test, and a nomogram for predicting M-HLH was constructed using multivariable binary logistic regression. The predictors were also ranked using decision-tree analysis. The nomogram and decision tree were validated in the validation cohort (10 patients with M-HLH and 16 patients with NM-HLH). Results: The ratio of the maximal standardized uptake value (SUVmax) of the lymph nodes to that of the mediastinum, the ratio of the SUVmax of bone lesions or bone marrow to that of the mediastinum, and age were selected for constructing the model. The nomogram showed good performance in predicting M-HLH in the validation cohort, with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.686-0.971). At an appropriate cutoff value, the sensitivity and specificity for identifying M-HLH were 90% (9/10) and 68.8% (11/16), respectively. The decision tree integrating the same variables showed 70% (7/10) sensitivity and 93.8% (15/16) specificity for identifying M-HLH. In comparison, visual analysis of ¹⁸F-FDG PET/CT images demonstrated 100% (10/10) sensitivity and 12.5% (2/16) specificity. Conclusion: ¹⁸F-FDG PET/CT may be a practical technique for identifying M-HLH. The model constructed using ¹⁸F-FDG PET/CT features and age was able to detect malignancy with better accuracy than visual analysis of ¹⁸F-FDG PET/CT images.

• The Korean Journal of Nuclear Medicine
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• v.36 no.2
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• pp.110-120
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• 2002

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied $[^{18}F]$ fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5 - 10.8 mU/mg), while SNU-C5 and monocytes showed lower range of hexokinase activity (4.3 - 6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.