FDG PET for grading malignancy in thymic epithelial tumors: Significant differences in FDG uptake and expression of glucose transporter-1 and hexokinase II between low and high-risk tumors: Preliminary study

Purpose

To evaluate ¹⁸F-fluorodeoxyglucose (FDG) uptake to predict the malignant nature and analyze the correlation between FDG uptake and expression of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in thymic epithelial tumors.

Materials and methods

Eleven patients with a thymic epithelial tumor who underwent FDG PET/CT before therapy were reviewed. The thymic tumors were classified by the WHO histological classification and Masaoka clinical staging. Comparison of maximum standardized uptake value (SUV_max) of the lesion was made between the low-risk (Type A, AB and B1) and high-risk {Type B2, B3 and C (thymic cancer)} groups and among clinical stages. Expression of Glut-1 and HK-II was analyzed immunohistochemically.

Results

All 11 tumors showed FDG uptake visually. SUV_max was significantly higher in the high-risk group (n = 5, 5.24 ± 2.44) than the low-risk group (n = 6, 3.05 ± 0.55) (P = 0.008). Staining scores of both Glut-1 and HK-II were significantly higher in the high-risk group than in the low-risk group (Glut1: P = 0.034 and HK-II: P = 0.036). There were no significant differences in SUV_max (P = 0.11), Glut-1 (P = 0.35) and HK-II scores (P = 0.29) among clinical stages. SUV_max was significantly correlated to each of the staining scores of Glut-1 (ρ = 0.68, P = 0.031) and HK-II (ρ = 0.72, P = 0.024).

Conclusion

These preliminary results support the previously published view that SUV_max may be useful to predict the malignant nature of thymic epitherial tumors and suggest that the degree of FDG uptake in the thymic epitherial tumors is closely related to the amount of Glut-1 and HK-II in the tumor.     

Dual-time point PET/CT with F-18 FDG for the differentiation of malignant and benign bone lesions

Purpose  The purpose of the present study was to evaluate whether 2-fluoro[fluorine-18]-2-deoxy-d-glucose (F-18 FDG) positron emission tomography (PET) could differentiate malignant and benign bone lesions and whether obtaining delayed F-18 FDG PET images could improve the accuracy of the technique. Methods  In a prospective study, 67 patients with bone lesions detected by computed tomography (CT) or magnetic resonance imaging were included. Whole body PET/CT imaging was performed at 1 h (early) after the F-18 FDG injection and delayed imaging at 2 h post injection was performed only in the abnormal region. Semiquantitative analysis was performed using maximum standardized uptake value (SUV_max), obtained from early and delayed images (SUV_maxE and SUV_maxD, respectively). The retention index (RI) was calculated according to the equation: RI = (SUV_maxD − SUV_maxE) × 100/SUV_maxE. Histopathology of surgical specimens and follow-up data were used as reference criteria. The SUV_maxE and RI were compared between benign and malignant lesions. Results  The final diagnoses revealed 53 malignant bone lesions in 37 patients and 45 benign lesions in 30 patients. There were statistically significant differences in the SUV_maxE between the malignant and benign lesions (P = 0.03). The mean SUV_maxE was 6.8 ± 4.7 for malignant lesions and 4.5 ± 3.3 for benign lesions. However, a considerable overlap in the SUV_maxE was observed between some benign and malignant tumors. With a cutoff value of 2.5 for the SUV_maxE, the sensitivity, specificity, and accuracy were 96.0%, 44.0%, and 72.4%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 67.1% and 90.9%, respectively. There were significant differences in the RI between the malignant and benign lesions (P = 0.004). But there was overlap between the two groups. The mean RI was 7 ± 11 for the benign lesions and 18 ± 11 for the malignant lesions. When an RI of 10 was used as the cutoff point, the sensitivity, specificity, and accuracy were 90.6%, 76.0%, and 83.7.0%, respectively. The PPV and NPV were 81.4% and 87.1%, respectively. Conclusions  The results of this study indicate that dual-time point F-18 FDG PET may provide more help in the differentiation of malignant tumors from benign ones.     

The clinical efficacy of <Superscript>18</Superscript>F-FDG-PET/CT in benign and malignant musculoskeletal tumors

Objective  Most of the current clinical data on the role of 2-[¹⁸F]fluoro-2-deoxy-d-glucose positron emission tomography (¹⁸F-FDG-PET) in musculoskeletal tumors come from patients studied with PET and less frequently with hardware fusion PET/computed tomography (CT). And the number of cases in each report is too small to clarify the exact clinical efficacy of PET or PET/CT. This prompted us to analyze our experience with ¹⁸F-FDG-PET/CT in a relatively large group of patients with musculoskeletal tumors. Methods   ¹⁸F-FDG-PET/CT was performed on 91 patients from May 2004 to June 2007. The final diagnosis was obtained from surgical biopsy in 83 patients (91%) and clinical follow-up in 8 (9%). We analyzed the characteristics and amount of ¹⁸F-FDG uptake in soft tissue and bone tumors, and investigated the ability of ¹⁸F-FDG-PET/CT to differentiate malignant from benign tumors. The cutoff maximum standardized uptake value (SUV_max) was calculated using the receiver-operation characteristic curve method. Sensitivity, specificity, and diagnostic accuracy were calculated with cutoff SUV_max and the final diagnosis. Unpaired t test was used for the statistical analysis. Results  Final diagnosis revealed 19 benign soft tissue tumors (mean SUV_max 4.7), 27 benign bone tumors (5.1), 25 malignant soft tissue tumors (8.8), and 20 malignant bone tumors (10.8). There was a significant difference in SUV_max between benign and malignant musculoskeletal tumors in total (P < 0.002), soft tissue tumors (P < 0.05), and bone tumors (P < 0.02). Sensitivity, specificity, and diagnostic accuracy were 80%, 65.2%, and 73% in total with cutoff SUV_max 3.8, 80%, 68.4%, and 75% in the soft tissue tumors with cutoff SUV_max 3.8, and 80%, 63%, and 70% in the bone tumors with cutoff SUV_max 3.7. Conclusions   ¹⁸F-FDG-PET/CT reliably differentiated malignant soft tissue and bone tumors from benign ones, although there were many false-positive and falsenegative lesions. Further studies with all kinds of musculoskeletal tumors in large numbers are needed to improve the diagnostic accuracy of ¹⁸F-FDG-PET/CT.     

Adrenal masses: the value of additional fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in differentiating between benign and malignant lesions

Objective  To investigate whether integrated fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) can differentiate benign from adrenal malignant lesions on the basis of maximum standardized uptake value (SUV_max), tumor/liver (T/L) SUV_max ratio, and CT attenuation value (Hounsfield Units; HU) of unenhanced CT obtained from FDG-PET/CT data. Methods  We studied 30 patients with 35 adrenal lesions (16 adrenal benign lesions, size 16 ± 5 mm, in 15 patients; and 19 adrenal malignant lesions, 24 ± 12 mm, in 15 patients) who had confirmed primary malignancies (lung cancer in 23 patients, lymphoma in 2, esophageal cancer in 2, hypopharyngeal cancer in 1, prostate cancer in 1, and 1 patient in whom lesions were detected at cancer screening). All patients underwent PET/CT at 1 h post FDG injection. Diagnosis of adrenal malignant lesions was based on interval growth or reduction after chemotherapy. An adrenal mass that remained unchanged for over 1 year was the standard used to diagnose adrenal benign lesions. Values of FDG uptake and CT attenuation were measured by placing volumetric regions of interest over PET/CT images. Adrenal uptake of SUV_max ≥ 2.5 was considered to indicate a malignant lesion; SUV_max < 2.5 was considered to indicate a benign lesion. In further analysis, 1.8 was employed as the threshold for the T/L SUV_max ratio. Unenhanced CT obtained from PET/CT data was considered positive for adrenal malignant lesions based on a CT attenuation value ≥ 10 HU; lesions with a value < 10 HU were considered adrenal benign lesions. Mann–Whitney’s U test was used for statistical analyses. Results  SUV_max in adrenal malignant lesions (7.4 ± 3.5) was higher than that in adrenal benign lesions (2.1 ± 0.5, p < 0.05). The CT attenuation value of adrenal malignant lesions (27.6 ± 11.9 HU) was higher than that of adrenal benign lesions (10.1 ± 12.3 HU, p < 0.05). In differentiating between adrenal benign and malignant lesions, a CT threshold of 10 HU corresponded to a sensitivity of 57%, specificity of 94%, accuracy of 74%, positive predictive value of 92% and negative predictive value of 65%. An SUV_max cut-off value of 2.5 corresponded to a sensitivity of 89%, specificity of 94%, accuracy of 91%, positive predictive value of 94% and negative predictive value of 88%. The T/L SUV_max ratio was 1.0 ± 0.2 for adrenal benign lesions and 4.5 ± 3.0 for adrenal malignant lesions. And T/L SUV_max ratio cut-off value of 1.8 corresponded to a sensitivity of 85%, specificity of 100%, accuracy of 91%, positive predictive value of 100% and negative predictive value of 83%. Conclusions  FDG-PET/CT with additional SUV_max analysis improves the diagnostic accuracy of adrenal lesions in cancer patients.     

Dual-time-point [18F]-FDG PET/CT in the diagnostic evaluation of suspicious breast lesions

Purpose

The authors sought to evaluate whether the reacquisition of images 3 h after administration of radiotracer improves the sensitivity of fluorine-18 fluorodeoxyglucose positron emission tomography computed tomography ([¹⁸F]-FDG PET/CT) in patients with suspicious breast lesions.

Materials and methods

Forty-eight patients with 59 breast lesions underwent an [¹⁸F]-FDG PET/CT study in the prone position with a dual-time-point acquisition performed in the early phase 1 h after FDG administration (PET-1) and in the delayed phase 3 h after FDG administration (PET-2). Both examinations were evaluated qualitatively and semiquantitatively with calculation of the mean percentage variation of the standard uptake values (Δ% SUV_max) between PET-1 and PET-2. All lesions with an SUV_max ≥2.5 at PET-1 or a reduction in SUV between PET-1 and PET-2 were considered benign. The definitive histopathological diagnosis was available for all patients included in the study.

Results

The dual-time-point acquisition of [¹⁸F]-FDG PET/CT displayed an accuracy of 85% for lesions with an SUV_max ≥2.5 and/or positive Δ% SUV_max, with sensitivity and specificity values of 81% and 100% compared with 69%, 63% (both p<0.001) and 100% (p=n.s.), respectively, for the single-time-point acquisition. Malignant lesions showed an increase in FDG uptake between PET-1 and PET-2, with a Δ% SUV_max of 10±7 (p<0.04). In contrast, benign lesions showed a decrease in SUV between PET-1 and PET-2, with aΔ% SUV_max of ?21±7 (p<0.001).

Conclusions

The delayed repeat acquisition of PET images improves the accuracy of [¹⁸F]-FDG PET/CT in patients with suspicious breast lesions with respect to the single-time-point acquisition. In addition, malignant breast lesions displayed an increase in FDG uptake over time, whereas benign lesions showed a reduction. These variations in FDG uptake between PET-1 and PET-2 are a reliable parameter that can be used for differentiating between benign and malignant breast lesions.     

Usefulness of a breath-holding acquisition method in PET/CT for pulmonary lesions

Objective  To evaluate the usefulness of a breath-holding (BH) ¹⁸F-2-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG-PET) technique for PET/computed tomography (CT) scanning of pulmonary lesions near the diaphragm, where image quality is influenced by respiratory motion. Methods  In a basic study, simulated breath-holding PET (sBH-PET) data were acquired by repeating image acquisition eight times with fixation of a phantom at 15 s/bed. Free-breathing PET (FB-PET) was simulated by acquiring data even as moving the phantom at 120 s/bed (sFB-PET). Images with total acquisition times of 15 s, 30 s, 45 s, 60 s, and 120 s were generated for sBHPET. Receiver-operating characteristic (ROC) analyses and determination of the statistical significance of differences between sFB-PET images and sBH-PET images were performed. A total of 22 pulmonary lesions in 21 patients (12 men and 9 women, mean age 61.3 ± 10.6 years, 10 benign lesions in 9 patients and 12 malignant lesions in 12 patients) were examined by FB-PET and BH-PET). For evaluation of these two acquisition methods, displacement of the lesion between CT and PET was considered to be a translation, and the statistical significance of differences in maximum standardized uptake value (SUV_max) of the lesion was assessed using the paired t test. Results  In the basic study, sBH-PET images with acquisition times of 45 s, 60 s, and 120 s had significantly higher diagnostic accuracy than 120-s sFB-PET images (P < 0.05). In clinical cases, translation of the BH-PET images was significantly lower than that of the FB-PET images (benign: 5.29 ± 4.02 mm vs. 11.79 ± 8.27 mm, P = 0.005; malignant: 4.29 ± 3.36 mm vs. 18.26 ± 12.31 mm, P = 0.003). The SUV_max of the lesions in the BH-PET images was significantly higher than that in the FB-PET images (benign: 2.40 ± 0.86 vs. 2.20 ± 0.85, P = 0.005; malignant: 4.84 ± 2.16 vs. 3.75 ± 2.11, P = 0.001). Conclusions  BH-PET provides images with better diagnostic accuracy, avoids image degradation owing to respiratory motion, and yields more accurate attenuation correction. This method is very useful for overcoming the problem of respiratory motion.     

Risk stratification and prediction of cancer of focal thyroid fluorodeoxyglucose uptake during cancer evaluation

Background  

Focal thyroid incidentaloma by F-18 2-deoxy-2-F18-fluoro-d-glucose (FDG) positron emission tomography (PET) has been reported 1–4% of cancer patients and normal healthy population, with a risk of cancer ranging 14–50%. The aim of this study was to investigate the prevalence of thyroid incidentaloma in F-18 FDG PET/CT and risk of cancer, usefulness of visual and SUV_max and SUV_mean differentiating malignant nodules and to define the predictable variables.     

Nonionic intravenous contrast agent does not cause clinically significant artifacts to <Superscript>18</Superscript>F-FDG PET/CT in patients with lung cancer

Objective This study was performed to evaluate the effects of intravenous (i.v.) contrast agent on semi-quantitative values and lymph node (LN) staging of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in patients with lung cancer. Methods Thirty-five patients with lung cancer were prospectively included. Whole-body PET and nonenhanced CT images were acquired 60 min following the i.v. injection of 370 MBq ¹⁸F-FDG and subsequently, enhanced-CT images were acquired with the i.v. administration of 400 mg iodinated contrast agent without positional change. PET images were reconstructed with both nonenhanced and enhanced CTs, and the maximum and average standardized uptake values (SUV_max and SUV_ave) calculated from lung masses, LNs, metastatic lesions, and normal structures were compared. To evaluate the effects of the i.v. contrast agent on LN staging, we compared the LN status on the basis of SUVs (cut-offs; SUV_max = 3.5, SUV_ave = 3.0). Results The mean differences of SUV_max in normal structures between enhanced and nonenhanced PET/CT were 15.23% ± 13.19% for contralateral lung, 8.53% ± 6.11% for aorta, 5.85% ± 4.99% for liver, 5.47% ± 6.81% for muscle, and 2.81% ± 3.05% for bone marrow, and those of SUV_ave were 10.17% ± 9.00%, 10.51% ± 7.89%, 4.95% ± 3.89%, 5.66% ± 9.12%, and 2.49% ± 2.50%, respectively. The mean differences of SUV_max between enhanced and nonenhanced PET/CT were 5.89% ± 3.92% for lung lesions (n = 41), 6.27% ± 3.79% for LNs (n = 76), and 3.55% ± 3.38% for metastatic lesions (n = 35), and those of SUV_ave were 3.22% ± 3.01%, 2.86% ± 1.71%, and 2.33% ± 3.95%, respectively. Although one LN status changed from benign to malignant because of contrast-related artifact, there was no up- or down-staging in any of the patients after contrast enhancement. Conclusions An i.v. contrast agent may be used in PET/CT without producing any clinically significant artifact.     

18F-FDG PET for the evaluation of thymic epithelial tumors: Correlation with the World Health Organization classification in addition to dual-time-point imaging

Purpose  Our aim was to determine dual-phase ¹⁸F-FDG PET imaging features for various subtypes of thymic epithelial tumors based on the World Health Organization classification. Methods  Forty-six patients with histologically verified thymic epithelial tumors [23 with low-risk tumors (4 with type A, 16 with AB, and 3 with B1) and 23 with high-risk tumors (7 with B2, 5 with B3, and 11 with thymic carcinoma] were enrolled in this study. All patients were injected with ¹⁸F-FDG.; after 1 h, they underwent scanning; after 3 h, 23 patients underwent an additional scanning. The maximum standard uptake value (SUV_max) and the retention index (RI%) of the lesions were determined. Results  The early and delayed SUV_max values in the patients with high-risk tumors [early SUV_max (mean: 6.0) and delayed SUV_max (mean: 7.4)] were both significantly larger than those in patients with low-risk tumors [early SUV_max (mean: 3.2) and delayed SUV_max (mean: 3.4)] (P < 0.05). Early SUV_max values of greater than 7.1 differentiated thymic carcinomas from other types of tumors. For the histological differentiation between high-risk tumors and low-risk tumors, an early SUV_max value of 4.5 was used as the cutoff. The sensitivity, specificity, and accuracy were 78.3, 91.3, and 84.8%, respectively. Conclusion  High SUV values (early SUV > 4.5) suggest the presence of high-risk tumors. A very high SUV value (early SUV > 7.1) is useful for the differentiation of thymic carcinomas from other types of tumors. The delayed SUV values were higher than the early SUV values in all types of tumors.     

Clinicopathological presentation of varying 18F-FDG uptake and expression of glucose transporter 1 and hexokinase II in cases of hepatocellular carcinoma and cholangiocellular carcinoma

We report the results of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) and immunohistochemical staining of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in patients with hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) to observe the variation in ¹⁸F-FDG uptake and variation in expression of Glut-1 and HK-II in these hepatic tumors. In the case of HCC, moderate ¹⁸F-FDG uptake and strong expression of HK-II were detected, whereas Glut-1 was not expressed. Conversely, CCC showed high ¹⁸F-FDG uptake and increased expression of Glut-1 but HK-II was not expressed. The variation in the ¹⁸F-FDG uptake and expression of Glut 1 and HK-II in HCC and CCC might be owing to the difference in origin and the different mechanisms involved in glucose uptake, rate of glucose transporters, and hexokinase activity involved in the glycolytic pathway.     

Prospective evaluation of solitary thyroid nodule on 18F-FDG PET/CT and high-resolution ultrasonography

Purpose

The utility of 18F-FDG PET/CT in the assessment of thyroid nodules is unclear as there are several conflicting reports on the usefulness of SUV as an indicator to distinguish benign from malignant thyroid lesions. This study incorporated an additional parameter, namely dual time point imaging, to determine the diagnostic accuracy of PET/CT imaging. The performance of 18F-FDG PET/CT was compared to that of high-resolution ultrasound which is routinely used for the evaluation of thyroid nodules.

Methods

Two hundred patients with incidentally detected solitary thyroid nodules were included in the study. Each patient underwent ultrasound and PET/CT evaluation within 7 days of each other, reported by an experienced radiologist and nuclear medicine specialist, respectively, in a blinded manner. The PET/CT criteria employed were maximum SUV (SUV_max) at 60 min and change in SUV_max at delayed (120 min) imaging. Final diagnosis was based on pathological evaluation and follow-up.

Results

Of the 200 patients, 26 had malignant and 174 had benign nodules. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of ultrasound were 80.8, 81.6, 39.6, 96.6 and 81.5%, respectively. Using SUV_max at 60 min as the diagnostic criterion, the above indices were 80.8, 84.5, 43.8, 96.7 and 84%, respectively, for PET/CT. The SUV_max of malignant thyroid lesions was significantly higher than benign lesions (16.2 ± 10.6 vs. 4.5 ± 3.1, respectively; p = 0.0001). Incorporation of percentage change in SUV_max at delayed imaging as the diagnostic criterion yielded a slightly improved sensitivity, specificity, PPV, NPV and accuracy of 84.6, 85.6, 46.8, 97.4 and 85.5%, respectively. There was a significant difference in percentage change in SUV_max between malignant and benign thyroid lesions (14.9 ± 11.4 vs. ?1.6 ± 13.7, respectively; p = 0.0001). However, there was no statistically significant difference (95% confidence interval) between the diagnostic performance of PET/CT and ultrasound.

Conclusions

Routine use of 18F-FDG PET/CT with SUV_max at 60 min as the sole diagnostic criterion does not appear to have a significant advantage over high-resolution ultrasound in the evaluation of thyroid nodules. Incorporation of dual time point imaging enhances image interpretation, and yields a higher diagnostic performance, yet it is not statistically significant. Bearing in mind the cost, limited availability and radiation exposure, routine use of 18F-FDG PET/CT for distinguishing benign from malignant thyroid nodules cannot be recommended.     

SUV navigator enables rapid [<Superscript>18</Superscript>F]-FDG PET/CT image interpretation compared with 2D ROI and 3D VOI evaluations

Purpose

Positron emission tomography (PET) and the maximum standardized uptake value (SUV_max) is a useful technique for assessing malignant tumors. Measurements of SUV_max in multiple lesions per patient frequently require many time-consuming procedures. To address this issue, we designed a novel interface named SUV Navigator (SUVnavi), and the purpose of this study was to investigate its utility.

Materials and methods

We measured SUV_max in 661 lesions from 100 patients with malignant tumors. Diagnoses and SUV_max measurements were made with SUVnavi, 2D, and 3D measurements. SUV measurement accuracy in each method were also evaluated.

Results

The average reduction in time with SUVnavi versus 2D was 53.8% and 3D was 37.5%; time required with SUVnavi was significantly shorter than with 2D and 3D (P < 0.001 and P < 0.001, respectively). The time reduction and lesion number had a positive correlation (P < 0.001 and P < 0.001, respectively). SUV_max agreed with precise SUV_max in all lesions measured with SUVnavi and 3D but in only 466 of 661 lesions (70.5%) measured with 2D.

Conclusion

SUVnavi may be useful for rapid [¹⁸F]-fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]-FDG PET/CT) image interpretation without reducing the accuracy of SUV_max measurement.

     

Expressions of glucose transporter Types 1 and 3 and hexokinase-II in diffuse large B-cell lymphoma and other B-cell non-Hodgkin's lymphomas

IntroductionDiffuse large B-cell lymphoma (DLBCL) has been reported to show higher uptake of 2-deoxy-2-F18-fluoro-d-glucose (FDG) by positron emission tomography than other B-cell non-Hodgkin's lymphomas (non-DLBCL). The authors addressed the mechanism of FDG uptake in DLBCL by immunostaining for glucose transporter Types 1 (Glut-1) and 3 (Glut-3) and hexokinase-II (HK-II) in excised lymphoma tissues.MethodsSixteen B-cell non-Hodgkin's lymphoma patients (11 DLBCL and 5 non-DLBCL patients) were included in the study because the lymphoma tissues obtained by excision were eligible for immunostaining. The expressions of Glut-1, Glut-3 and HK-II were assessed regarding the percentages of positively stained lymphoma cells (%expression), the staining intensities (none=0, weak=1, moderate=2 and strong=3) and the staining patterns (membranous or cytoplasmic) and compared between DLBCL and non-DLBCL.ResultsGlut-1 was not expressed at all in DLBCL or non-DLBCL, and their Glut-3 expressions were not significantly different (P>.05) with respect to %expression (mean±S.E.M., 73.6±7.3% vs. 72.0±3.7%), staining intensity (2.5±0.2 vs. 2.6±0.2) and staining pattern (membranous pattern dominant; 54.5% vs. 60.0%). However, DLBCL expressed more HK-II than non-DLBCL, i.e., %expression (45.2±11.5% vs. 17.0±15.8%, P=.0275) and staining intensity (2.3±0.2 vs. 0.6±0.4, P=.0032). HK-II showed a cytoplasmic location in DLBCL and non-DLBCL.ConclusionsHK-II and Glut-3 contribute significantly to FDG uptake in DLBCL. DLBCL may have higher FDG uptake because it expresses more HK-II, whereas Glut-1 appears to play no role in FDG uptake in B-cell non-Hodgkin's lymphoma.     

Assessment of FDG retention differences between the FDG-avid benign pulmonary lesion and primary lung cancer using dual-time-point FDG-PET imaging

Purpose

The aim of this study was to clarify FDG retention differences between FDG-avid benign pulmonary lesions (BPLs) and primary lung cancers (PLCs), and between tuberculous and non-tuberculous BPLs using dual-time-point FDG-PET imaging.

Methods

Thirty-four BPLs and 47 PLCs with a maximal standardized uptake value (SUVmax) >2.5 and a maximal axial diameter >10 mm were enrolled. We compared the retention index (RI) among different types of lesions, and evaluated the relationship between RI and SUV_max at 1 h (SUV₁). Glucose transporter-1 (Glut-1) and hexokinase (HK)-2 expression was assessed in eight non-tuberculous BPLs.

Results

BPLs and PLCs showed similar high RIs (mean ± SD 33.6 ± 22.6 and 32.5 ± 23.7, respectively; p = 0.95). In BPLs, both tuberculous and non-tuberculous lesions showed high RIs (39.1 ± 25.8 and 30.3 ± 20.3, respectively; p = 0.43). However, BPLs and PLCs exhibited a different relationship between RI and SUV₁. BPLs tended to show lower RIs with higher SUV₁s, and a mild negative correlation, whereas PLCs showed persistent high RIs and no significant correlation. Glut-1 and HK-2 expression was found in 75 and 12.5 % of non-tuberculous BPLs, respectively.

Conclusions

FDG-avid BPLs could show high RIs regardless of their being tuberculous and non-tuberculous lesions, and no significant difference with PLC RIs was found. FDG-avid BPLs and PLCs showed different relationships between RI and SUV₁, and it seemed to be related with different mechanisms of high FDG retention. However, the mechanisms of high FDG retention in FDG-avid BPLs remain unclear, and this matter requires further investigation.     

Current generation time-of-flight <Superscript>18</Superscript>F-FDG PET/CT provides higher SUVs for normal adrenal glands,while maintaining an accurate characterization of benign and malignant glands

Objective

Modern PET/CT scanners have significantly improved detectors and fast time-of-flight (TOF) performance and this may improve clinical performance. The aim of this study was to analyze the impact of a current generation TOF PET/CT scanner on standardized uptake values (SUV), lesion-background contrast and characterization of the adrenal glands in patients with suspected lung cancer, in comparison with literature data and commonly used SUV cut-off levels.

Methods

We included 149 adrenal glands from 88 patients with suspected lung cancer, who underwent ¹⁸F-FDG PET/CT. We measured the SUV_max in the adrenal gland and compared this with liver SUV_mean to calculate the adrenal-to-liver ratio (AL ratio). Results were compared with literature derived with older scanners, with SUV_max values of 1.0 and 1.8 for normal glands [1, 2]. Final diagnosis was based on histological proof or follow-up imaging. We proposed cut-off values for optimal separation of benign from malignant glands.

Results

In 127 benign and 22 malignant adrenal glands, SUV_max values were 2.3 ± 0.7 (mean ± SD) and 7.8 ± 3.2 respectively (p < 0.01). Corresponding AL ratios were 1.0 ± 0.3 and 3.5 ± 1.4 respectively (p < 0.01). With a SUV_max cut-off value of 3.7, 96 % sensitivity and 96 % specificity was reached. An AL ratio cut-off value of 1.8 resulted in 91 % sensitivity and 97 % specificity. The ability of both SUV_max and AL ratio to separate benign from malignant glands was similar (AUC 0.989 vs. 0.993, p = 0.22).

Conclusions

Compared with literature based on the previous generation of PET scanners, current generation TOF ¹⁸F-FDG PET/CT imaging provides higher SUVs for benign adrenal glands, while it maintains a highly accurate distinction between benign and malignant glands. Clinical implementation of current generation TOF PET/CT requires not only the use of higher cut-off levels but also visual adaptation by PET readers.

     

Risk assessment in liposarcoma patients based on FDG PET imaging

Purpose Tumor grade and subtype are considered standard parameters for risk assessment in patients with liposarcoma. The aim of this study was to assess the clinical value of [¹⁸F]fluorodeoxyglucose (FDG) PET-derived maximum standardized uptake value (SUV_max) for prediction of outcome in liposarcoma patients.Methods ¹⁸F-FDG PET was performed in 54 patients with liposarcoma prior to therapy. SUV_max was calculated for each tumor and results were correlated with tumor grade, subtype, and relapse-free survival.Results SUV_max ranged from 0.4 to 15.9 (mean 3.6) and was significantly lower in grade I than in grade II and grade III tumors. SUV_max was 2.3±1.7, 3.5±1.5, 4.8±2.5, and 5.6±5.8 in well-differentiated, myxoid/round cell, dedifferentiated, and pleomorphic subtypes, respectively. Borderline differences (p=0.059) were found between tumor SUV_max in patients with and without relapse. Using a SUV of 3.6 as cut-off, the accuracy in predicting a relapse was 75%. Tumor grade yielded a lower accuracy for predicting relapse (50%), as did tumor subtype (35%). In Kaplan-Meier survival analysis, patients with a SUV_max >3.6 had a significantly shorter disease-free survival of 21 months compared with 44 months in patients with a SUV_max ≤3.6. Tumor grading and tumor subtype did not yield significant differences.Conclusion Pretherapy tumor SUV obtained by FDG PET imaging was a more useful parameter for risk assessment in liposarcoma than tumor grade or subtype. A SUV_max of more than 3.6 resulted in a significantly reduced disease-free survival and identified patients at high risk for developing early local recurrences or metastatic disease.     

<Superscript>18</Superscript>F-FDG and <Superscript>18</Superscript>F-FLT PET/CT imaging in the characterization of mediastinal lymph nodes

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently ¹⁸F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) and ¹⁸F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUV_max of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUV_max was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUV_max values (p > 0.05) or FLT SUV_max values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUV_max and FLT SUV_max of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though ¹⁸F-FLT PET/CT and ¹⁸F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUV_max values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.

     

The additional value of CT images interpretation in the differential diagnosis of benign vs. malignant primary bone lesions with 18F-FDG-PET/CT

Objective  To evaluate the value of a dedicated interpretation of the CT images in the differential diagnosis of benign vs. malignant primary bone lesions with 18fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). Materials and methods  In 50 consecutive patients (21 women, 29 men, mean age 36.9, age range 11–72) with suspected primary bone neoplasm conventional radiographs and 18F-FDG-PET/CT were performed. Differentiation of benign and malignant lesions was separately performed on conventional radiographs, PET alone (PET), and PET/CT with specific evaluation of the CT part. Histology served as the standard of reference in 46 cases, clinical, and imaging follow-up in four cases. Results  According to the standard of reference, conventional 17 lesions were benign and 33 malignant. Sensitivity, specificity, and accuracy in assessment of malignancy was 85%, 65% and 78% for conventional radiographs, 85%, 35% and 68% for PET alone and 91%, 77% and 86% for combined PET/CT. Median SUV_max was 3.5 for benign lesions (range 1.6–8.0) and 5.7 (range 0.8–41.7) for malignant lesions. In eight patients with bone lesions with high FDG-uptake (SUV_max ≥ 2.5) dedicated CT interpretation led to the correct diagnosis of a benign lesion (three fibrous dysplasias, two osteomyelitis, one aneurysmatic bone cyst, one fibrous cortical defect, 1 phosphaturic mesenchymal tumor). In four patients with lesions with low FDG-uptake (SUV_max < 2.5) dedicated CT interpretation led to the correct diagnosis of a malignant lesion (three chondrosarcomas and one leiomyosarcoma). Combined PET/CT was significantly more accurate in the differentiation of benign and malignant lesions than PET alone (p = .039). There was no significant difference between PET/CT and conventional radiographs (p = .625). Conclusion  Dedicated interpretation of the CT part significantly improved the performance of FDG-PET/CT in differentiation of benign and malignant primary bone lesions compared to PET alone. PET/CT more commonly differentiated benign from malignant primary bone lesions compared with conventional radiographs, but this difference was not significant.     

Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor.

The biologic mechanisms involved in the intratumoral heterogeneous distribution of 18F-FDG have not been fully investigated. To clarify factors inducing heterogeneous 18F-FDG distribution, we determined the intratumoral distribution of 18F-FDG by autoradiography (ARG) and compared it with the regional expression levels of glucose transporters Glut-1 and Glut-3 and hexokinase-II (HK-II) in a rat model of malignant tumor. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle (n = 7). Tumor tissues were excised 1 h after the intravenous injection of 18F-FDG and sectioned to obtain 2 adjacent slices for ARG and histochemical studies. The regions of interest (ROIs) were placed on ARG images to cover mainly the central (CT) and peripheral (PT) regions of viable tumor tissues and necrotic/apoptotic (NA) regions. The radioactivity in each ROI was analyzed quantitatively using a computerized imaging analysis system. The expression levels of Glut-1, Glut-3, and HK-II were determined by immunostaining and semiquantitative evaluation. The hypoxia-inducible factor 1 (HIF-1) was also immunostained. RESULTS: ARG images showed that intratumoral 18F-FDG distribution was heterogeneous. The accumulation of 18F-FDG in the CT region was the highest, which was 1.6 and 2.3 times higher than those in the PT and NA regions, respectively (P < 0.001). The expression levels of Glut-1, Glut-3, and HK-II were markedly higher in the CT region (P < 0.001) compared with those in the PT region. The intratumoral distribution of 18F-FDG significantly correlated with the expression levels of Glut-1, Glut-3, and HK-II (r = 0.923, P < 0.001 for Glut-1; r = 0.829, P < 0.001 for Glut-3; and r = 0.764, P < 0.01 for HK-II). The positive staining of HIF-1 was observed in the CT region. CONCLUSION: These results demonstrate that intratumoral 18F-FDG distribution corresponds well to the expression levels of Glut-1, Glut-3, and HK-II. The elevated expression levels of Glut-1, Glut-3, and HK-II, induced by hypoxia (HIF-1), may be contributing factors to the higher 18F-FDG accumulation in the CT region.     

False positive 18F-FDG PET in an ischial chondroblastoma; an analysis of glucose transporter 1 and hexokinase II expression

We report a rare case of chondroblastoma arising from the ischium which showed an increased ¹⁸F-FDG uptake. Chondroblastoma is an uncommon lesion and usually involves the epiphysis of long bones. However, in this case, the tumor appeared as a well-defined osteolytic lesion in the ischium on radiographs. MR imaging demonstrated two components in the tumor: a solid one and a multilobular cystic component. ¹⁸F-FDG PET imaging revealed an increased uptake in the ischium. The ¹⁸F-FDG uptake resembled the results observed in malignant bone tumors. A histological diagnosis of chondroblastoma was obtained from tissue of an open biopsy. An immunohistochemical analysis demonstrated weak expression of both Glut-1 and HK-II. These findings suggest that Glut-1 and HK-II expression are not strongly related to FDG uptake in chondroblastoma.