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.     

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.     

18F-FDG-PET of musculoskeletal tumors: a correlation with the expression of glucose transporter 1 and hexokinase II

Objective  It remains controversial whether positron emission tomography (PET) with 2-deoxy-2-[F-18]fluoro-d-glucose (F-18-FDG) can differentiate between benign and malignant musculoskeletal tumors. To uncover the mechanism of F-18-FDG accumulations, we analyzed the correlation between the F-18-FDG accumulation and the expression of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in benign and malignant musculoskeletal tumors. Methods  The maximum standardized uptake values (SUV_max) of F-18-FDG in 24 benign and 26 malignant musculoskeletal tumors were compared with the histologic malignancies, and the expression of Glut-1 and HK-II was analyzed by immunohistochemistry. Results  The SUV_max for malignant tumors (6.33 ± 4.79) was significantly higher than those with benign tumors (3.47 ± 3.12, P < 0.01). The expression of Glut-1 was high in 12 patients (all malignant) and low in 38 patients (24 benign and 14 malignant), and the expression of HK-II was high in 36 patients (11 benign and 25 malignant) and low in 14 patients (13 benign and 1 malignant). Cases with high expression of Glut-1 and HK-II at immunohistochemistry showed a higher SUV_max than those with low expression (Glut-1 8.03 ± 5.10 and 3.98 ± 3.53, P < 0.01; HK-II 5.73 ± 4.49 and 2.99 ± 3.02, P < 0.01). No significant dividing threshold of the SUV_max of F-18 FDG was found for the differential diagnosis between benign and malignant tumors or for the expression of Glut-1 and HK-II. Conclusions  The limited capability of F-18 FDG-PET in the differential diagnosis of musculoskeletal tumors is owing partly to the various levels of Glut-1 and HK-II expression in individual tumors.     

18F-FDG uptake in squamous cell carcinoma of the cervix is correlated with glucose transporter 1 expression.

This prospective study investigates the relationship between glucose transporter-1 (Glut-1) expression and PET images using (18)F-FDG and its uptake and compares them with the tumor status (primary vs. recurrent or persistent), initial grade of histologic differentiation, and International Federation of Gynecologic Obstetrics (FIGO) staging for cervical cancer patients. METHODS: A dual-phase (18)F-FDG PET scan was performed on 51 participants within the 2 wk before surgery or biopsy. (18)F-FDG uptake was quantified by calculating standardized uptake values (SUVs). After (18)F-FDG PET scanning, 51 histologically proven squamous cell carcinoma specimens were examined to determine their degree of differentiation, using hematoxylin and eosin staining, and the expression of Glut-1 by an immunohistochemical stain. Twenty normal cervical and 20 cervical intraepithelial neoplasia (CIN) sets of tissue were also used to compare the results of Glut-1 expression in these tissues. The expression of Glut-1 was the product of (the intensity [with grades 0-3, defined qualitatively]) with (percentages of the lesion area that were positive). The results of Glut-1 expression were analyzed in combination with the SUVs (SUV1 was that at 40 min and SUV2 was that at 3 h), tumor status, initial cell differentiation, and FIGO staging. RESULTS: Significant overexpression of Glut-1 was noted in 48 of the 51 (94.1%) cancer specimens. None or only minimal expression of Glut-1 was observed in basal layers of normal and CIN tissues. Significant positive correlation was observed between Glut-1 expression and the SUVs in cervical cancer specimens (r = 0.74, P < 0.000 for SUV1 and r = 0.65, P < 0.000 for SUV2). In recurrent or persistent tumor, tumor size was significantly associated with both Glut-1 expression (r = 0.508, P = 0.011) and SUV1 (r = 0. 456, P = 0.025). For recurrent or persistent tumor, only SUV1 reached statistical significance when compared with lymph node metastasis (P = 0.0226). CONCLUSION: Glut-1 expression was related to (18)F-FDG uptake in cervical cancer patients. Recurrent or persistent cervical cancer tumor had significantly higher Glut-1 expression than metastatic lymph nodes. The values of SUV and the expression of Glut-1 did not correlate with the initial grade of histologic differentiation and FIGO staging.     

Intratumoral Heterogeneous F-18 Fluorodeoxyglucose Uptake Corresponds with Glucose Transporter-1 and Ki-67 Expression in a Case of Krukenberg Tumor: Localization of Intratumoral Hypermetabolic Focus by Fused PET/MR Image

The expression of glucose transporters (Glut-1, Glut-3), hexokinase-II, and Ki-67 has been proposed to explain intratumoral heterogeneous F-18 fluorodeoxyglucose (FDG) uptake. We report a case of Krukenberg tumor with intratumoral heterogeneous FDG uptake which corresponded well with the expression levels of Glut-1 and ki-67. Fused positron emission tomography (PET)/magnetic resonance (MR) imaging was helpful for localizing the metabolically active area in the tumor specimen. This report elucidates the relationship between the intratumoral heterogeneous FDG uptake and biologic heterogeneity, and shows the usefulness of PET/MR in research on intratumoral heterogeneity.     

Relations Between Pathological Markers and Radioiodine Scan and 18F-FDG PET/CT Findings in Papillary Thyroid Cancer Patients With Recurrent Cervical Nodal Metastases

Purpose

The aim of this study was to investigate relationships between the immunohistochemical results and radioiodine scan and ¹⁸F-FDG PET findings in papillary thyroid cancer (PTC) patients with recurrent cervical nodal metastases.

Methods

A total of 46 PTC patients who had undergone a radioiodine scan and/or ¹⁸F-FDG PET/CT and a subsequent operation on recurrent cervical lymph nodes were enrolled. Twenty-seven patients underwent ¹⁸F-FDG PET/CT, 8 underwent radioiodine scans, and 11 underwent both scans. In all surgical specimens, the immunoexpressions of thyroglobulin (Tg), sodium-iodide symporter (NIS), glucose transporter 1 (Glut-1), and somatostatin receptor 1 and 2A (SSTR1 and SSTR2A) were assessed, and associations between these expressions and radioiodine scan and ¹⁸F-FDG PET findings were evaluated.

Results

Of the 38 patients who underwent ¹⁸F-FDG PET/CT, all patients with weak Tg expression had positive ¹⁸F-FDG uptake, while only 45 % of the patients with moderate or strong Tg expression showed positive uptake (p = 0.01). The proportion of patients with positive ¹⁸F-FDG uptake increased as the degree of Glut-1 expression with luminal accentuation increased. Of the 19 patients who underwent a radioiodine scan, the proportion with positive radioiodine uptake was greater among patients with strong NIS and SSTR2A expression than among patients expressing these markers at weak levels (p = 0.04 for all). All three patients with weak Tg expression were negative for radioiodine uptake.

Conclusion

The ¹⁸F-FDG uptakes of recurrent cervical nodes are related to strong Glut-1 expression with luminal accentuation and weak Tg expression, whereas radioiodine uptake is related to the strong expressions of NIS and SSTR2A.     

Relationship between retention index in dual-phase (18)F-FDG PET, and hexokinase-II and glucose transporter-1 expression in pancreatic cancer.

Recently, some studies have shown that delayed scanning with (18)F-FDG PET may help to differentiate malignant from benign pancreatic lesions. However, no study has evaluated the relationship between temporal changes in (18)F-FDG uptake and expression of hexokinase or glucose transporter. METHODS: Twenty-one consecutive patients with pancreatic cancer were studied preoperatively by dual-phase (18)F-FDG PET, performed 1 and 2 h after injection of (18)F-FDG. The standardized uptake value (SUV) of the pancreatic cancer was determined, and the retention index (RI) (%) was calculated by subtracting the SUV at 1 h (SUV1) from the SUV at 2 h (SUV2) and dividing by SUV1. The percentages of cells strongly expressing hexokinase type-II (HK-II) and glucose transporter-1 (GLUT-1) were scored on a 5-point scale (1 = 0%-20%, 2 = 20%-40%, 3 = 40%-60%, 4 = 60%-80%, 5 = 80%-100%) by visual analysis of immunohistochemical staining of paraffin sections from the tumor specimens using anti-HK-II and anti-GLUT-1 antibody (HK-index and G-index, respectively). RESULTS: SUV2 (mean +/- SD, 5.7 +/- 2.6) was higher than SUV1 (5.1 +/- 2.1), with an RI of 8.5 +/- 11.0. Four cases of cancer, in which SUV2 showed a decline from SUV1, showed a low HK-index (1.8 +/- 1.1), whereas 4 cases with an RI of > or =20 and 13 cases with an intermediate RI (0-20) showed significantly higher HK-indices (4.3 +/- 0.7 and 3.1 +/- 1.5, respectively; P < 0.05). RI showed a positive correlation with HK-index, with an R(2) of 0.27 (P < 0.05), but no significant correlation with the G-index. SUV1 showed no relationship with the HK-index but showed a weak positive correlation with the G-index, with an R(2) of 0.05 (P = 0.055). CONCLUSION: These preliminary findings suggest that the RI obtained from dual-phase (18)F-FDG PET can predict HK-II expression and that the SUV (at 1 h) has a positive correlation with GLUT-1 expression but not with HK-II expression.     

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.     

大鼠C6胶质瘤放射治疗前后^18F—FDG摄取水平变化与多种生物学指标的相关性研究

目的探讨大鼠C6胶质瘤放疗前后^18F-FDG摄取水平变化及其与肿瘤细胞密度、Glut、细胞增殖及血管生成的关系。方法30只雄性荷C6胶质瘤SD大鼠按随机数字表法分为A、B和C3组,每组10只,均接种肿瘤细胞。2周后,A组行^18F-FDG PET／CT显像,B和C组分别于放疗后48h、1周行^18F-FDG PET／CT显像,计算肿瘤与对侧脊柱旁肌肉的SUVmax比值（TIM）,观察放疗前后肿瘤TIM的变化。显像后处死大鼠,取出肿瘤组织,观察组织病理变化,并计数肿瘤细胞密度,免疫组织化学法测定肿瘤Ki67标记指数（Ki67 LI）及微血管密度（MVD）,Western blot法检测Glut-1及VEGF的表达,采用单因素方差分析比较放疗前后T／M及各指标的变化,双变量相关分析评价T／M变化与各生物学指标间的相关性。结果（1）A、B、C3组T／M、肿瘤细胞密度、Ki67LI、MVD、Glut-1及VEGF水平总体比较组间差异均有统计学意义（F值依次为6．77,60．66,104．56,95．49,9．13和24．48,P均〈0．05）。两两比较示,B组T／M（9．23±4．56）、肿瘤细胞密度（672．70±92．98）及Ki67 LI（18．56±2．26）与A组（10．86±3．31,730．50±78．93,20．02±2．14）差异无统计学意义（P均〉0．05）,C组（5．16±2．52,355．60±72．62,7．81±1．76）与A、B2组相比下降明显,差异均有统计学意义（P均〈0．05）;B组MVD（19．50±1．96）及Glut-1水平（0．20±0．09）较A组（17．90±2．02,0．15±0．04）差异无统计学意义（P均〉0．05）,C组该两指标（8．40±1．84,0．07±0．06）显著下降,且与A、B2组间差异均有统计学意义（P均〈0．05）。B组肿瘤VEGF表达（0．42±0．13）与A组、C组（分别为0．17±0．04,0．16±0．09）相比显著增高,差异均有统计学意义（P均〈0．05）。（2）A、B组间T／M变化与肿瘤细胞密度变化呈明显正相关（r=0．81,P〈0．05）;A、C组间T／M变化与肿瘤细胞密度、Ki67 LI、MVD、Glut-1的变化呈正相关（r分别为0．83,0．71,0．68,0．62,P均〈0．05）。结论大鼠C6胶质瘤放疗后^18F—FDG摄取水平变化在放疗后48h仅与肿瘤细胞密度变化相关,而放疗后1周则能体现放疗引起的肿瘤多种生物学改变。     

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 FDG PET/CT and FDG uptake and related enzymes in lymphadenopathies: preliminary results

Purpose

The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with ¹⁸F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed.

Methods

Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60 min and 180 min after FDG administration). FDG-avid nodal lesions were segmented to yield volume and standardized uptake values (SUV), including SUVmax, SUVmean, cSUVmean (with partial volume correction), total lesion glycolysis (TLG) and cTLG (with partial volume correction). Expression of glucose transporter-1 (GLUT-1), hexokinase-II (HK-II), glucose-6-phosphatase (G6Pase) and hypoxia-inducible factor-1alpha (HIF-1alpha) were assessed with immunohistochemistry and enzyme activity was determined for HK and G6Pase.

Results

FDG uptake was assessed in 203 lesions (146 malignant and 57 benign). Besides volume, there were significant increases over time for all parameters, with generally higher levels in the malignant lesions. The retention index (RI) was not able to discriminate between malignant and benign lesions. Volume, SUVmax, TLG and cTLG for both scans were able to discriminate between the two groups statistically, but without complete separation. Glucose metabolism/hypoxia markers were assessed in 15 lesions. TLG and cTLG were correlated with GLUT-1 expression on the 60-min scan. RI-max and RI-mean and SUVmax, SUVmean and cSUVmean on the 60-min scan were significantly correlated with HK-II expression.

Conclusion

RI was not able to discriminate between malignant and benign lesions, but some of the SUVs were able to discriminate on the 60-min and 180-min scans. Furthermore, FDG uptake was correlated with GLUT-1 and HK-II expression.

     

Correlation of Glut-1 glucose transporter expression with

Positron emission tomography (PET) with [18F]2-fluoro-2-deoxy-D-glucose (FDG) may show negative results for bronchioloalveolar lung carcinoma. We investigated the correlation of Glut-1 glucose transporter expression with [18F]FDG uptake in non-small cell lung cancer. Thirty-two patients with 34 non-small cell lung cancers (7 bronchioloalveolar carcinomas, 23 non-bronchioloalveolar adenocarcinomas, 3 squamous cell carcinomas, and 1 adenosquamous cell carcinoma) were studied. Final diagnoses were established by histology (via thoracotomy) in all patients. [18F]FDG PET was performed 40 min after i.v. injection of 185 MBq [18F]FDG. For semi-quantitative analysis of [18F]FDG uptake, standardized uptake values (SUVs) were calculated. Glut-1 expression was studied in terms of the immunohistochemistry of paraffin sections using anti-Glut-1 antibody to determine the intensity (0-3) of Glut-1 immunoreactivity and percentage of the Glut-1-positive area. Of seven bronchioloalveolar carcinomas, six (85.7%) were negative for the expression of Glut-1, while only one (4.3%) of 23 non-bronchioloalveolar adenocarcinomas was negative (P < 0.0001). The percentages of Glut-1-positive area, as well as the SUVs, were significantly lower in bronchioloalveolar carcinomas (n = 7) (2.86% +/- 7.56% and 1.25 +/- 0.75, respectively) than in non-bronchioloalveolar adenocarcinomas (n = 23) (54.83% +/- 25.64%, P < 0.0001, and 3.94 +/- 1.93, P = 0.001, respectively). The degree of cell differentiation correlated with the percentage of Glut-1-positive area and SUVs in adenocarcinoma of the lung. Correlations between SUVs and the intensity of Glut-1 immunoreactivity were also significant (intensities 0 and 1, n = 11, SUV 1.47 +/- 0.63; intensities 2 and 3, n=23, SUV 4.78 +/- 2.13; P < 0.0001). The percentage of Glut-1-positive area correlated significantly with SUVs (n = 34, r = 0.658, P < 0.01). Overexpression of Glut-1 correlated with high [18F]FDG uptake. These findings suggest that Glut-1 expression is related to [18F]FDG uptake in non-small cell lung cancer. Glut-1 expression, as well as [18F]FDG uptake, correlated with the degree of cell differentiation in adenocarcinomas, and both Glut-1 expression and [18F]FDG uptake were significantly lower in bronchioloalveolar carcinomas than in non-bronchioloalveolar carcinomas.     

Characterization of plaques using 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1.

High tissue matrix metalloproteinase (MMP) activity has been associated with advanced atherosclerosis and plaque rupture. 18F-FDG uptake has been reported to detect inflammation. This investigation examined the vascular 18F-FDG uptake by PET/CT and its correlation with circulating MMP-1 levels. METHODS: We examined 25 consecutive patients with significant carotid stenosis and 22 healthy control subjects using 18F-FDG PET/CT. The leukocyte counts, C-reactive protein (CRP), and MMP-1 were measured. RESULTS: 18F-FDG arterial uptake, as well as calcifications, was significantly higher in extensive distributions in patients with established carotid stenosis. However, their distribution was not consistently overlapping. The values of circulating MMP-1 and leukocyte counts were significantly higher in patients with carotid stenosis (all P < 0.05). In addition, subjects with higher 18F-FDG uptake (maximum SUV > 2.0) in target lesions had higher baseline and poststenting MMP-1 levels (all P < 0.05). CONCLUSION: We provide a link between 18F-FDG uptake and circulating MMP-1. 18F-FDG PET/CT could be used as an adjunct to the clinical management of high-risk atherosclerosis and an in vivo tool to study plaque biology.     

Breast cancer staging in a single session: whole-body PET/CT mammography

Our objective was to compare the diagnostic accuracy of an all-in-one protocol of whole-body 18F-FDG PET/CT and integrated 18F-FDG PET/CT mammography with the diagnostic accuracy of a multimodality algorithm for initial breast cancer staging. METHODS: Forty women (mean age, 58.3 y; range, 30.8-78.4 y; SD, 12 y) with suspected breast cancer were included. For the primary tumor, we compared 18F-FDG PET/CT mammography versus MRI mammography; for axillary lymph node status, 18F-FDG PET/CT versus clinical investigation and ultrasound; and for distant metastases, 18F-FDG PET/CT versus a multimodality staging algorithm. Histopathology and clinical follow-up served as the standard of reference. The Fisher exact test evaluated the significance of differences (P < 0.05). Alterations in patient management caused by 18F-FDG PET/CT were documented. RESULTS: No significant differences were found in the detection rate of breast cancer lesions (18F-FDG PET/CT, 95%; MRI, 100%; P = 1). 18F-FDG PET/CT correctly classified lesion focality significantly more often than did MRI (18F-FDG PET/CT, 79%; MRI, 73%; P < 0.001). MRI correctly defined the T stage significantly more often than did 18F-FDG PET/CT (MRI, 77%; 18F-FDG PET/CT, 54%; P = 0.001). 18F-FDG PET/CT detected axillary lymph node metastases in 80% of cases; clinical investigation/ultrasound, in 70%. This difference was not statistically significant (P = 0.067). Distant metastases were detected with 18F-FDG PET/CT in 100% of cases, and the multimodality algorithm identified distant metastases in 70%. This difference was not statistically significant (P = 1). Three patients had extraaxillary lymph node metastases that were detected only by PET/CT (cervical, retroperitoneal, mediastinal/internal mammary group). 18F-FDG PET/CT changed patient management in 12.5% of cases. CONCLUSION: Our data suggest that a whole-body 18F-FDG PET/CT mammography protocol may be used for staging breast cancer in a single session. This initial assessment of the 18F-FDG PET/CT protocol indicates similar accuracy to MRI for the detection of breast cancer lesions. Although MRI seems to be more accurate when assessing the T stage of the tumor, 18F-FDG PET/CT seems able to more accurately define lesion focality. Although 18F-FDG PET/CT mammography was able to detect axillary lymph node metastases with a high sensitivity, this method cannot soon be expected to replace the combination of clinical examination, ultrasound, and sentinel lymph node biopsy for axillary assessment.     

The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at diagnosis

The aim of this study was to determine whether the use of whole-body (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET)/CT alters staging and management of nasopharyngeal carcinoma (NPC) when compared with current staging practice. 52 patients with Stage III-IV NPC without distant metastases on chest X-ray/CT, abdominal ultrasound or bone scan were recruited for the study. Whole-body (18)F-FDG PET/CT and MRI of the head and neck were performed. The scans were compared for extent of the primary tumour (PT), cervical nodal metastases (CNM) and distant metastases (DM). Any discordance in results was assessed with respect to staging and impact on management. MRI and (18)F-FDG PET/CT scans were discordant in 28 (54%) patients. There was discordance in the extent of PT at 28 sites; in all sites, MRI showed more extensive tumour involving the nasopharynx (n = 8), skull base (n = 14), brain (n = 4) and orbit (n = 2). There was also variation among the extent of CNM in four nodes of the retropharyngeal region, with the nodes being positive on MRI. (18)F-FDG PET /CT did not identify any additional distant metastases but did identify a second primary tumour in the colon. The additional use of (18)F-FDG PET/CT did not "up-stage" the overall stage or change management in any patient. In conclusion, there is discordance between MRI and (18)F-FDG PET/CT, and the additional use of (18)F-FDG PET/CT for the current assessment of NPC at diagnosis does not appear to be justified in this cohort of patients.     

18F-DOPA positron emission tomography for tumour detection in patients with medullary thyroid carcinoma and elevated calcitonin levels

In spite of the availability of numerous procedures, diagnostic imaging of tumour manifestations in patients with medullary thyroid carcinoma and elevated calcitonin levels is often difficult. In the present study, the new procedure of fluorine-18 dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) was compared with the established functional and morphological imaging methods. After evaluation of the normal distribution of 18F-DOPA, 11 patients with medullary thyroid carcinoma were examined using 18F-DOPA PET. Results of 18F-fluorodeoxyglucose (18F-FDG) PET, somatostatin receptor scintigraphy (SRS) and morphological tomographic imaging (CT/MRI) were available for all patients. All individual procedures were evaluated without reference to prior information. Data assessment for each patient was based on cooperation between experienced radiologists and specialists in nuclear medicine, who considered all the available findings (histological results, imaging, follow-up studies). This cooperation served as the gold standard against which the results of the individual procedures were evaluated. A total of 27 tumours were studied [three primary tumours (PT)/local recurrence (LR), 16 lymph node metastases (LNM) and eight organ metastases (OM)]. 18F-DOPA PET produced 17 true-positive findings (2 PT/LR, 14 LNM, 1 OM), 18F-FDG PET 12 (2 PT/LR, 7 LNM, 3 OM), SRS 14 (2 PT/LR, 8 LNM, 4 OM) and morphological imaging 22 (3 PT/LR, 11 LNM, 8 OM). The following sensitivities were calculated with respect to total tumour manifestations: 18F-DOPA PET 63%, 18F-FDG PET 44%, SRS 52%, morphological imaging 81%. Thus, the morphological imaging procedures produce the best overall sensitivity, but the specificity for PT/LR (55%) and LNM (57%) was low. With respect to lymph node staging, the best results were obtained with 18F-DOPA PET. 18F-DOPA PET is a new functional imaging procedure for medullary thyroid carcinoma that seems to provide better results than SRS and 18F-FDG PET. Moreover, the data indicate that no single procedure provides adequate diagnostic certainty. Therefore, 18F-DOPA PET is a useful supplement to morphological diagnostic imaging, improving lymph node staging and enabling a more specific diagnosis of primary tumour and local recurrence.     

^18F—FDG PET／CT评价弥漫性大B细胞淋巴瘤化疗中期的治疗反应

目的探讨^18F-FDGPET／CT评价弥漫性大B细胞淋巴瘤（DLBCL）患者化疗中期治疗反应的价值。方法DLBCL初诊患者53例,采用环磷酰胺＋阿霉素＋长春新碱＋泼尼松（CHOP）或利妥苷单克隆抗体＋环磷酰胺＋阿霉素＋长春新碱＋泼尼松（R-CHOP）方案化疗,分别于化疗前和化疗中期（4个疗程后）进行^18F-FDGPET／CT显像。根据肿瘤对化疗的反应将病例分为完全反应组、部分反应组和无反应组,比较3组患者的完全缓解率。用SPSS13．0软件进行统计学分析,完全缓解率的比较用x2检验。结果完全反应组、部分反应组和无反应组的临床完全缓解率分别为88．5％（23／26）、73．3％（11／15）和8．3％（1／12）,3组问差异有统计学意义（X2=23．548,P=0．000）。完全反应组、部分反应组的完全缓解率高于无反应组（X2=22．656,P=0．000和x2=11．407,P=0．001）。结论DLBCL患者化疗中期^18F-FDG PET／CT显像有助于预测其化疗疗效。     

18F-FDG uptake by primary tumor as a predictor of intratumoral lymphatic vessel invasion and lymph node involvement in non-small cell lung cancer: analysis of a multicenter study.

Intratumoral lymphatic vessel invasion and lymph node involvement are important factors in the planning of therapeutic strategies, particularly limited surgical resection in patients with non-small cell lung cancer. (18)F-FDG uptake within the primary lesion correlates with aggressiveness on PET studies. The more metabolically active the tumor, the more aggressive are the findings. The aim of this multicenter study was to determine whether (18)F-FDG uptake of the primary tumor is a predictor of intratumoral lymphatic vessel invasion and lymph node metastasis in patients with non-small cell lung cancer. METHODS: One hundred thirty-two patients with lung cancer were studied. All patients underwent a thoracotomy within 4 wk of the (18)F-FDG PET study. A 3-point visual scoring system (low, moderate, or high grade in comparison with mediastinal activity) was used to interpret (18)F-FDG uptake within the primary lesions. The degree of (18)F-FDG uptake in the primary tumor was correlated with the incidence of intratumoral lymphatic vessel invasion and lymph node involvement. Multivariate analysis was performed with logistic multivariate analysis to assess the joint effects and interactions of the variables (age, sex, tumor size, histology, and (18)F-FDG uptake) on intratumoral lymphatic vessel invasion and lymph node involvement. RESULTS: Intratumoral lymphatic vessel invasion and lymph node involvement were found in 7.1% and 5.9%, respectively, of the patients classified in the low-grade group, and in 14.3% and 10.0%, respectively, of the patients classified in the moderate-grade group. In contrast, of the patients classified in the group with high (18)F-FDG uptake, intratumoral lymphatic vessel invasion and lymph node involvement were found in 39.7% and 38.9%, respectively. Multivariate analysis showed that only (18)F-FDG uptake was a significant factor for intratumoral lymphatic vessel invasion and that tumor size and (18)F-FDG uptake were significant factors for lymph node involvement. Of the patients in the high-grade group whose tumors were classified as > or =3 cm in size, lymph node involvement was found in 51.5%. In contrast, of the patients in the low- to moderate-grade group whose tumors were classified as <3 cm in size, lymph node involvement was found in only 9.1% (P < 0.0001). CONCLUSION: Patients with a low to moderate (18)F-FDG uptake in the primary lesion had a significantly lower risk of concurrent intratumoral lymphatic vessel invasion and nodal involvement than did patients with a high (18)F-FDG uptake. In patients with non-small cell lung cancer, (18)F-FDG uptake by the primary tumor is a strong predictor of intratumoral lymphatic vessel invasion and lymph node metastasis.     

^18F-FDG符合线路显像在胸腺上皮肿瘤诊断中的应用价值

目的探讨^18F-脱氧葡萄糖（FDG）符合线路显像在胸腺上皮肿瘤（TET）诊断中的价值。方法回顾性分析37例TET患者的^18F—FDG符合线路显像结果,图像分析采用视觉分析及半定量方法[肿瘤／正常肺组织放射性比值（TLR）]。按WHO TET病理学分类结果将患者分成3组（高生存率组,包括A、AB、B1型;中生存率组,包括B2、B3型;低生存率组,包括胸腺癌）;同时将^18F—FDG显像结果与增强CT影像进行对比,TLR与免疫组织化学检查所测Ki67标记指数（细胞增殖指标）进行相关性分析。组间TLR比较采用方差分析。结果（1）^18F—FDG符合线路显像阳性率91．9％（34／37）;（2）3个不同生存率组TLR间差异有统计学意义（高、中、低生存率组TLR依次为：1．42±0．27,2．13±0．74,3．00±1．19,F=9．99,P〈0．05）;（3）TLR与Ki67标记指数有明显相关性（r=0．613,P=0．002）;（4）^18F-FDG显像发现2例增强CT未发现的病灶,病灶分别位于前胸壁和右锁骨上淋巴结;（5）共有4例伴发重症肌无力。结论^18F—FDG符合线路显像有助于WHO TET病理学分类和发现更多的TET侵犯、转移灶;可以用^18F—FDG在TET的浓聚程度反映细胞的增殖活力。     

Thyroglobulin levels and thyroglobulin doubling time independently predict a positive 18F-FDG PET/CT scan in patients with biochemical recurrence of differentiated thyroid carcinoma

Purpose

To assess the relationship between serum thyroglobulin (Tg) levels, Tg doubling time (Tg-DT) and the diagnostic performance of ¹⁸F-FDG PET/CT in detecting recurrences of ¹³¹I-negative differentiated thyroid carcinoma (DTC).

Methods

Included in the present study were 102 patients with DTC. All patients were treated by thyroid ablation (e.g. thyroidectomy and ¹³¹I), and underwent ¹⁸F-FDG PET/CT due to detectable Tg levels and negative conventional imaging. Consecutive serum Tg measurements performed before the ¹⁸F-FDG PET/CT examination were used for Tg-DT calculation. The ¹⁸F-FDG PET/CT results were assessed as true or false after histological and/or clinical follow-up.

Results

Serum Tg levels were higher in patients with a positive ¹⁸F-FDG PET/CT scan (median 6.7 ng/mL, range 0.7–73.6 ng/mL) than in patients with a negative scan (median 1.8 ng/mL, range 0.5–4.9 ng/mL; P?<?0.001). In 43 (88 %) of 49 patients with a true-positive ¹⁸F-FDG PET/CT scan, the Tg levels were >5.5 ng/mL, and in 31 (74 %) of 42 patients with a true-negative ¹⁸F-FDG PET/CT scan, the Tg levels were ≤5.5 ng/mL. A Tg-DT of <1 year was found in 46 of 49 patients (94 %) with a true-positive ¹⁸F-FDG PET/CT scan, and 40 of 42 patients (95 %) with a true-negative scan had a stable or increased Tg-DT. Moreover, combining Tg levels and Tg-DT as selection criteria correctly distinguished between patients with a positive and a negative scan (P<0.0001).

Conclusion

The accuracy of ¹⁸F-FDG PET/CT significantly improves when the serum Tg level is above 5.5 ng/mL during levothyroxine treatment or when the Tg-DT is less than 1 year, independent of the absolute value.