ª Springer Science+Business Media New York 2016

Abdominal Radiology

Abdom Radiol (2016) DOI: 10.1007/s00261-016-0788-6

FLT-PET/CT diagnosis of primary and metastatic nodal lesions of gastric cancer: comparison with FDG-PET/CT Masatoyo Nakajo,1,2 Yoriko Kajiya,2 Atushi Tani,2 Megumi Jinguji,1 Masayuki Nakajo,2 Takashi Yoshiura1 1

Department of Radiology, Kagoshima University, Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan 2 Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima 892-8512, Japan

Abstract Purpose: To examine the diagnostic performance of 18Ffluorothymidine (FLT)-PET/CT of primary and metastatic nodal lesions of gastric cancer by comparing with 18 F-fluorodeoxyglucose (FDG)-PET/CT. Methods: The enrolled study population comprised 17 patients with 17 newly diagnosed gastric cancers who underwent surgery of the primary lesion and regional nodes after both FDG- and FLT-PET/CT scans. Visual detectability of the primary gastric lesions was correlated with pathological factors using the Fisher exact or Mann–Whitney U test. The sensitivity, specificity, and accuracy in detecting nodal lesions were compared between both PET/CT scans using the McNemar exact or v2 test. Results: Fourteen of 17 (82.4%) primary cancers were visualized by both FDG- and FLT-PET/CT scans. Although FDG or FLT visibility was not significantly associated with tumor size (p = 0.16) or histological type (p = 1.00), the 3 nonvisible lesions were pathologically early (T1) cancers. The sensitivity, specificity, and accuracy for detecting nodal metastasis were 44.8% (13/29), 98.7% (164/166), and 90.8% (177/195) for FDG-PET/CT, and 31.0% (9/29), 100% (166/166), and 89.7% (175/195) for FLT-PET/CT, respectively. No significant difference was found between the two scans in sensitivity (p = 0.13), specificity (p = 0.48), or accuracy (p = 1.00). Conclusion: FLT-PET/CT may have the same diagnostic value as FDG-PET/CT for detection of primary and nodal lesions of gastric cancer.

Correspondence to: Masatoyo Nakajo; email: toyo.nakajo@dol phin.ocn.ne.jp

Key words: Gastric cancer—Lymph node metastasis—FDG—FLT—PET/CT

Gastric cancer is one of the leading causes of cancer morbidity and mortality, and the second most common cause of cancer-related death [1]. To date, the curative therapy of gastric cancer has mainly relied on the completed tumor resection. Thus, early diagnosis and accurate staging are important for decision making in treatment of gastric cancer. Computed tomography (CT) has been used for preoperative staging of gastric cancer, however, it has a limited accuracy in staging of lymph node (node) which is one of the most important prognostic factors [2]. Glucose analogue 18F-fluorodeoxyglucose (FDG) represents the lesion glycolytic activity and has been widely used as a tracer of positron emission tomography (PET) [3] and PET/CT in oncology [4]. Several studies have compared FDG-PET/CT and CT diagnostic performances in the preoperative staging of gastric cancer. These studies have shown that the sensitivity of FDGPET/CT is lower and the specificity is higher than CT in the detection of regional nodal metastases [5–7]. Although no significant difference was observed in the accuracy between them, the usefulness of FDG-PET/CT in the staging of gastric cancer is still controversial [5–7]. Three¢-deoxy-3¢-18F-fluorothymidine (FLT) was developed as a tracer for cell proliferation. It is phosphorylated by the cytosolic enzyme thymidine kinase 1 (TK-1) and trapped in the cell and FLT uptake is positively correlated with cell growth and TK1 activity [8, 9]. Thus, FLT can image cell proliferation in vivo and has been used for noninvasive assessment of proliferation

M. Nakajo et al.: FLT-PET/CT diagnosis of primary and metastatic

activity of several types of cancers [10] including gastric cancers [11–15]. Although FLT uptake was compared with FDG uptake in primary gastric cancers [11–14], no study has directly compared FDG- and FLT-PET/CT scans in the diagnosis of metastatic nodal lesions of gastric cancer based on the pathological results. The aim of this study was to examine the diagnostic performance of FLT-PET/CT for metastatic nodes as well as primary lesions of gastric cancer by comparing with FDG-PET/CT.

Materials and methods Patients This prospective study was approved by the institutional review board. The study group consisted of consecutive patients referred to our hospital for treatment of gastric cancer. Patients were eligible for the study if they underwent whole-body PET/CT scans with both FDG and FLT, and subsequent surgical resection of the primary lesion and regional nodes. Since pathological findings of the removed specimens were standards of reference, patients were excluded from this study if they did not undergo surgical resection, or they underwent chemotherapy or radiotherapy before surgery. From October 2010 to April 2012, 134 patients were referred to our hospital for treatment of gastric cancers which were confirmed by endoscopy and biopsy. One hundred seventeen patients were excluded because of the following reasons: no PET/CT study performed (n = 75), only FDG-PET/CT performed due to refusal of FLT-PET/CT (n = 38), and choice of chemotherapy (n = 4). Finally, 17 patients (13 men and 4 women: mean age, 66 ± 10 years [range, 47-82]) with 17 gastric cancers were enrolled. Written informed consent was obtained from each patient. A total of 195 regional nodes were resected and the mean number of resected nodes per primary lesion was 12 ± 2 (range: 9–13).

Imaging protocols PET/CT scans were performed using a PET/CT system (Discovery STE; GE Medical Systems, Milwaukee, WI). All patients were instructed to fast for at least 5 h before each PET/CT examination. Image acquisition started approximately 1 h after intravenous injection of FDG (3.7 MBq/kg) or FLT (3.7 MBq/kg). The patients were asked to take orally 500 mL of water or green tee during 1 h from each tracer injection to scan starting. At FDG injection, their mean plasma glucose level was 103 mg/ dL (range, 78–144 mg/dL). FLT was synthesized using the method described by Oh et al. [16]. The radiochemical purity and specific activity of the produced FLT were >95% and >1 Ci/lmol, respectively. CT from the brain to the pelvis was performed immediately before PET scan with a multi-detector spiral CT scanner (3.75 mm

slice thickness, a pitch of 1.75, 120 keV and auto mA [30200 mA depending on the patient’s total body mass]). Whole-body PET scan was performed, covering an area identical to that covered by CT. Acquisition time was 2.5 min per bed position with 8 bed positions. Emission data were reconstructed with a 3-dimensional (3D) ordered-subset expectation maximization algorithm (VUE Point Plus, 28 subsets, 2 iterations) to 128 9 128 matrices using the CT data for attenuation correction. The reconstructed transaxial spatial resolution for PET was 5.1 mm FWHM in-plane. Ten patients were performed FDG-PET/CT first. The mean interval between both tracer PET/CT scans was 6 ± 5 days (range, 1–16 days). All patients underwent radical surgery between 4 and 28 (mean, 14 ± 7) days after completion of both PET/CT scans.

Histological analysis Surgical specimens including the dissected stomach and nodes were examined to determine maximum tumor size, depth of invasion, histological type, and nodal metastasis by an experienced pathologist without knowledge of the PET/CT findings. The pathological tumor stages were determined by the American Joint Committee on Cancer TNM classification system [17]. The histological types were classified according to the classification of Lauren with modification [18, 19]. This classification differentiates only between intestinal (gland formation) and nonintestinal tumors.

Image analysis PET/CT images were displayed at the workstation (Advantage Windows Workstation; GE Healthcare, Milwaukee, WI). Two nuclear medicine radiologists, who knew the purpose of PET/CT examinations, but were blinded to pathological results, independently interpreted PET/CT images. The observers read either FDG or FLT-PET/CT image set in the first reading session, and the other image set in the second session after an interval of 4 weeks. They scored visually the uptake of each lesion using a five-point scale [20] as follows: 0, no visible uptake; 1, uptake weaker than normal surrounding organs; 2, mild uptake between 1 and 3; 3, FDG uptake similar to liver uptake and FLT uptake similar to vertebral uptake; and 4, FDG uptake higher than liver uptake and FLT uptake higher than vertebral uptake. During the interpretation, the observers used both the CT images and fused PET/CT images to identify the primary lesion and regional nodes. In cases of disagreement, consensus was made by the two readers and the third nuclear medicine radiologist. For determination of diagnostic performance, scores 0 and 1 were negative, and scores 2–4 were positive. The nodal staging analysis was applied for the 17 gastric cancers; N1: positive FDG

M. Nakajo et al.: FLT-PET/CT diagnosis of primary and metastatic

or FLT uptake in 1–2 regional nodes, N2: positive uptake in 3–6 regional nodes, N3: positive uptake in 7 or more regional nodes. Semiquantitative analyses of visible primary tumors and visible regional nodes were performed using maximum standardized uptake value (SUVmax) by the fourth nuclear medicine radiologist according to the interpreted results of visual assessment. SUVmax was automatically recorded as follows: First, a rectangular 3D-search region of interest (ROI) was drawn around the visible tumor in a suitable reference transaxial plane, excluding the adjacent avid nonmalignant structures. The volume of interest (VOI) was then defined adapting an orthogonal ROI on the sagittal plane to encompass the craniocaudal extent of the tumor and on the coronal plane to encompass the mediolateral extent of the tumor. VOI setting was performed over the consented positive lesions. SUVmax was defined as the maximum tissue concentration of FDG (kBq/mL) or FLT (kBq/mL) in the structure delineated by the VOI divided by the activity injected per gram body weight (kBq/g). The software (Advantage Windows Workstation; GE Healthcare, Milwaukee, WI) provided this value automatically.

Statistical analysis Pathological findings were the standards of reference. The PET interpreted results and pathological results were correlated by two nuclear medicine radiologists in consensus. The Mann–Whitney U or Wilcoxon signedrank test was used to assess the differences between two quantitative variables. The Spearman rank correlation was used to assess the relationship between two quantitative variables. The Fisher exact test was used to assess the association between categorical variables. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated for diagnosing nodal metastasis, and compared between FDG and FLT by the McNemar’s or v2 test. Statistical power was estimated using the sensitivity difference in nodal metastasis between FDG- and FLT-PET/CT scans. A mean value was expressed with a standard deviation. To evaluate interobserver agreement on image interpretation, j-statistics were used [21]. A value of p < 0.05 was considered as statistically significant and all p values presented are two-sided. The statistical analyses were performed using the MedCalc Statistical Software (MedCalc Software, Mariakerke, Belgium).

Results The pathological findings of 17 gastric adenocarcinomas were as follows: maximum tumor size (mean; 82.5 ± 40.1 mm, range; 30.0–160 mm); 5 T1, 1 T2, 1 T3,

and 10 T4 tumors; 7 intestinal and 10 nonintestinal tumors; 7 N0, 4 N1, 6 N2, and 0 N3 tumors and no M1 tumors.

Interobserver agreement on PET/CT image interpretation In visual scoring, the interobserver agreement between the two radiologists was perfect for both FDG (j = 1.00, no disagreement) and FLT (j = 1.00, no disagreement) on the primary lesion basis and almost perfect for FDG (j = 0.85, 3 disagreed nodes) and substantial agreement for FLT (j = 0.74, 4 disagreed nodes) on the node basis.

FDG- and FLT-PET/CT findings of primary cancers Fourteen (82.4%) of 17 primary cancers were positive on both FDG- and FLT-PET/CT scans, and the residual 3 primary cancers were negative by both scans. All these 3 negative lesions were pathologically T1. The FDG or FLT visibility was not significantly associated with tumor size [negative vs. positive: mean; 41.0 ± 22.5 (range: 15.0– 55.0) mm vs. 82.1 ± 40.0 (range: 30.0–160) mm, p = 0.16] or histological type [the positive rate: Lauren classification: intestinal tumor, 85.7% (6/7) vs. nonintestinal tumor, 80.0% (8/10), p = 1.00]. The visual score was significantly lower for FLT (mean; 2.5 ± 1.1, range; 0–4) than for FDG (mean; 3.3 ± 1.6, range; 0–4) (p = 0.008). SUVmax was significantly lower for FLT (mean; 7.1 ± 4.0, range; 3.4–18.1) than for FDG (mean; 10.2 ± 5.0, range; 4.2–21.0) (p = 0.003) in the 14 positive primary lesions. In only one primary cancer, FLTSUVmax exceeded FDG-SUVmax. FDG- and FLTSUVmax values significantly correlated with the tumor size (FDG-SUVmax: q = 0.59, p = 0.025, FLT-SUVmax: q = 0.56, p = 0.036). Table 1 shows associations of SUVmax with pathological factors. Neither FDG- nor FLT-SUVmax was significantly correlated with the depth of invasion or histological type.

Diagnostic performances of FDG- and FLTPET/CT scans for nodal metastasis A total of 195 regional nodes were dissected in the 17 patients. Metastasis was microscopically noted in 29 nodes of 10 patients. We noted 13 true positive (TP), 16 false-negative (FN), 2 false-positive (FP), and 164 truenegative (TN) nodes on FDG-PET/CT, and 9 TP, 20 FN, 0 FP, and 166 TN nodes on FLT-PET/CT, respectively (Table 2). Nodal staging (Table 3) was correct in 11 (64.7%) of 17 patients on FDG-PET/CT. There were 1 overstaged and 5 understaged cases. It was correct in 11 (64.7%) of 17 patients on FLT-PET/CT. There were 6 understaged cases.

M. Nakajo et al.: FLT-PET/CT diagnosis of primary and metastatic

Table 1. Relationships between primary lesion FDG-SUVmax or FLT-SUVmax and pathological factors in 14 visible gastric cancers Number All Depth of invasion T1, T2, T3 T4 Histological type Intestinal Nonintestinal

FDG-SUVmax

p value

FLT-SUVmax

p value

14

10.2 ± 5.0

– 0.20

7.1 ± 4.0

0.003 0.52

4 10

7.7 ± 4.1 11.1 ± 5.3

6 8

10.7 ± 6.6 9.8 ± 3.9

4.7 ± 0.9 8.1 ± 4.4 0.85

0.95 6.5 ± 2.8 7.6 ± 4.8

Table 2. Results of FDG and FLT uptake in lymph nodes of gastric cancer Metastasis

Radiotracer FDG uptake

Positive Negative Total

Total

Positive

Negative

13 2 15

16 164 180

FLT uptake

29 166 195

Total

Positive

Negative

9 0 9

20 166 186

29 166 195

Data are the number of lesions

Table 3. Diagnostic performances of FDG- and FLT-PET/CT examinations for N staging of gastric cancer Histology

FDG-PET/CT N0 N1 N2 N3 Total FLT-PET/CT N0 N1 N2 N3 Total

N0

N1

N2

N3

Total

6 1 0 0 7

1 3 0 0 4

2 2 2 0 6

0 0 0 0 0

9 6 2 0 17

7 0 0 0 7

1 3 0 0 4

3 2 1 0 6

0 0 0 0 0

11 5 1 0 17

Data are the number of primary lesions

Table 4. Diagnostic performances of FDG- and FLT-PET/CT examinations for detection of lymph node metastases from gastric cancer

Sensitivity Specificity PPV NPV Accuracy

FDG-PET/CTa

FLT-PET/CTa

p value

44.8% [13/29] (26.4, 64.3) 98.7% [164/166] (95.7, 99.9) 86.7%[13/15] (59.5, 98.3) 91.1% [164/180] (86.0, 94.8) 90.8% [177/195] (85.8, 94.4)

31.0% [9/29] (15.3, 50.8) 100% [166/166] (97.8, 100) 100% [9/9] (66.4,100) 89.2% [166/186] (83.9, 93.3) 89.7% [175/195] (84.6, 93.6)

0.13 0.48 0.25 0.55 1.00

a

Numbers in parentheses are 95% confidence intervals and numbers in brackets are number of lesions NPV, negative predictive value; PPV, positive predictive value

In the node-based analysis (Table 4), the sensitivity, specificity, PPV, NPV, and accuracy for detecting nodal metastasis were 44.8, 98.7, 86.7, 91.1, and 90.8% for FDG-PET/CT, and 31.0, 100, 100, 89.2, and 89.7% for FLT-PET/CT, respectively. No diagnostic indices showed significant difference between both scans (p = 0.13–1.00).

On FDG-PET/CT, the nodal size was significantly larger in 13 TP nodes (mean; 18.8 ± 6.2 mm, range; 12– 32 mm) than 16 FN nodes (mean; 4.8 ± 1.3 mm, range; 2–7 mm) (p < 0.001). There was a significant correlation between SUVmax and size in 13 FDG-TP nodes (q = 0.88, p < 0.001). In the 2 FDG-FP nodes, pathological evaluation revealed chronic inflammation

M. Nakajo et al.: FLT-PET/CT diagnosis of primary and metastatic

On FLT-PET/CT, the nodal size was significantly larger in 9 TP (mean; 19.7 ± 7.0 mm, range; 12-32 mm) than 20 FN nodes (mean; 7.2 ± 5.3 mm, range; 223 mm) (p = 0.002). There was a significant correlation between SUVmax and size in 12 FLT-TP nodes (q = 0.93, p < 0.001). The power analysis showed that our sample size of 195 nodes had 81.5% power, and the statistical powers were over 80%, which supported the validity of the sample size in this study. Representative images are shown in Figs. 1, 2, and 3, respectively.

Discussion FDG- and FLT-PET/CT findings of primary gastric cancers In our present study, 14 (82.4%) of 17 primary cancers were visible on both FDG- and FLT-PET/CT scans. The 3 nonvisible tumors were pathologically T1. Previous FDG-PET/CT studies have shown that gastric cancers limited to the mucosa or submucosa (T1 lesions), are less likely to be detected than more advanced T2–T4 lesions. Reported FDG sensitivity for detection of early gastric cancers (T1) ranges from 26% to 63%, whereas that for more advanced cancers (T2–T4) ranges from 83% to 98% [22]. Herrmann et al. [11] compared FLT-PET and FDGPET/CT studies and reported that FLT uptake was visible in all 45 advanced gastric cancers (100%), whereas FDG uptake was visible in 31/45 (69%); 16 (59%) of 27 with signet ring cells and 15 (83%) of 18 without signet ring cells. Kameyama et al. [12] reported that FLT and FDG uptake was visible in 20 (95.2%) and 19 (95.0%) of 21 advanced gastric cancers, respectively. Zhou et al. [13] also reported both high FLT (92.3%) and FDG (94.9%) sensitivities for detection of primary lesions of 39 patients with metastatic gastric cancers. Malkowski et al. [14] also reported 95% FLT sensitivity (89/94) for newly diagnosed advanced gastric cancer. These results suggest that the FLT sensitivity may be the same as the FDG sensitivity for detection of advanced gastric cancers. Tumor size has been reported to influence on the FDG-PET visibility of primary gastric cancer [22, 23]. For small lesions, the visibility is low due to the limited spatial resolution of PET. In our study, the mean size of the nonvisible tumors was smaller than that of visible tumors, although the difference was not statistically significant. In the 14 visible tumors, both FDG- and FLT-SUVmax values of primary gastric cancers were significantly associated with tumor size. Tumor size mainly depends on the number of viable cells as a result of cell proliferation. The number of viable cells which accumulate FDG or FLT increases according to tumor size which is one of the most important factors affecting SUV as well as tracer density [24]. No significant association of FDG-SUVmax with the depth of invasion in primary gastric cancer was reported

Fig. 1. A 78-year-old man with gastric cancer (T3) and regional metastatic node. Both FDG-PET/CT A and FLT-PET/ CT B images show positive FDG (score 4) and FLT uptake (score 3) in gastric cancer (FDG-SUVmax; 10.6, FLT-SUV max; 6.0, arrows), and positive FDG (score 3) and FLT (score 3) uptake in the metastatic regional node (arrowheads).

in the previous reports [24, 25]. In this connection, there was no significant difference in FDG-SUVmax between 4 T1–T3 and 10 T4 visible tumors (p = 0.20), although the former SUVmax (7.7 ± 4.1) was lower than the latter SUVmax (11.1 ± 5.3) in our study. There were no available data about the relationship between FLTSUVmax and the depth of invasion in primary gastric cancer, although the primary gastric cancer FLT-SUVmax was lower in the 4 T1–T3 tumors (4.7 ± 0.9) than in the 10 T4 tumours (8.1 ± 4.4) without significant difference (p = 0.52) in our study. Thus, further studies are necessary to clarify the relationship between the FLTSUVmax and the depth of invasion in gastric cancer. The modified Lauren histological (intestinal and nonintestinal) types have been reported to influence on the FDG-PET visibility of primary gastric cancer [22, 23]. Stahl et al. [18] reported that the FDG detection rate of intestinal tumors was significantly higher than that of

M. Nakajo et al.: FLT-PET/CT diagnosis of primary and metastatic

A 79-year-old man with gastric cancer (T4) and regional metastatic node. Both FDG-PET/CT A, B and FLTPET/CT C, D images show positive FDG (score 4) and FLT uptake (score 2) in the gastric cancer (FDG-SUVmax; 4.8, FLT-SUV max; 3.6, arrows), and negative FDG (score 0) and FLT (score 0) uptake in the metastatic regional node (arrowheads).

b Fig. 2.

Fig. 3. A 76-year-old woman with gastric cancer (T1) and chronic inflammation in a regional node. FDG-PET/CT A image shows false-positive FDG uptake (score 3) in the chronic inflammatory regional node (arrow). FLT-PET/CT B image shows true-negative FLT uptake (score 0) in the regional node (score 0, arrow). Primary lesion was false negative on both imaging.

nonintestinal tumors, and this difference might be influenced by the abundance of intra- and extracellular mucus content and the lack of glucose transporter 1

expression on the cell membrane of the nonintestinal tumors. On the other hand, Kameyama et al. [12] reported that there was no significant difference in FDG visibility between intestinal [92% (11/12)] and nonintestinal [100% (8/8)] tumors like ours [intestinal tumours, 86% (6/7) vs. nonintestinal tumors, 80% (8/10)]. In our study, neither FDG-SUVmax nor FLT-SUVmax of primary gastric cancers was significantly associated with the histological type. The FDG-SUV of intestinal tumors was reported to be significantly higher than that of nonintestinal tumors [18, 26]. However, no significant association between FDG-SUVmax of pri-

M. Nakajo et al.: FLT-PET/CT diagnosis of primary and metastatic

mary gastric cancers and the histological type was also reported [12, 27]. Therefore, the relationship between FDG-SUV and the histological type has not been consistent across the studies. On the other hand, no significant difference in the gastric cancer FLT-SUVmax between the histological types was reported in the 2 previous studies [11, 12] like ours. In our study, FLT-SUVmax was significantly lower than FDG-SUVmax in primary gastric cancers. The significantly lower FLT uptake compared with FDG uptake has been observed in primary gastric cancers [11, 12] and other primary cancers [28, 29]. Malignant viable tumors consist of nonproliferating and proliferating cells, and FDG accumulates in viable cells comprised nonproliferating and proliferating cells. On the other hand, thymidine, an analogue of FLT accumulates mainly in Sphase cells of proliferating cells [30, 31]. Additionally, the possible explanations for the lower uptake of FLT include (1) The halogen substitution in the 3’ position of FLT results in a decreased affinity for the pyrimidine transporter as compared with thymidine, (2) FLT is lower than thymidine in the affinity for TK1, and (3) Although plasma levels are low, thymidine may compete with FLT for the active site of nucleoside carriers in cell membranes and also for the active site of the trapping enzyme TK1 [29, 32].

Diagnostic performances of FDG- and FLTPET/CT scans for nodal metastasis In our study, nodal staging was correct in 65% of patients on both FDG- and FLT-PET/CT scans. About FDG-PET/CT, Ha et al. [25] reported that nodal staging was correct in 56/78 (71.8%) gastric cancer patients, which was similar to our result. The sensitivity and specificity of FDG-PET/CT for nodal metastasis have been reported as 41%–65% and 86%–100%, [5, 24] respectively. In our study, the sensitivity and specificity for detecting nodal metastasis were 44.8% and 98.7% for FDG-PET/CT. The high FN rate may be mainly attributed to the limited spatial resolution of PET component. In fact, the mean size of FDG FN nodes was significantly smaller than that of FDG TP nodes in our study. About FLT-PET/CT, to our knowledge, there was only one study which investigated nodal staging in gastric cancer by FLT-PET/CT [15]. Nodal staging was correct in 15 (71.4%) of 21 patients, which was similar to our result. In the node-based analysis, FLT-PET/CT detected 9 (31%) of 29 metastatic nodes in our study. The low sensitivity may be also mainly attributed to the limited spatial resolution of PET component. The specificity of FLT-PET/CT (100%; 166/166) was slightly better than FDG-PET/CT (98.7%, 164/166). The 2 FDG-FP and FLT-TN nodes had pathologically chronic inflamma-

tion. The better specificity of FLT-PET/CT compared to FDG-PET/CT was also reported in pulmonary lesions [20] and pancreatic cancers [33]. Although our study disclosed relatively lower sensitivity and higher specificity of FLT-PET/CT compared to FDG-PET/CT in detecting nodal metastases, these differences were not statistically significant. Thus our results failed to demonstrate clinical superiority of FLTPET/CT to FDG-PET/CT in assessing the primary and lymph node lesions of gastric cancer. In addition, the main drawback of FLT-PET/CT is the low detection rates of liver and bone metastases due to high normal liver and bone marrow FLT uptake [13]. Thus FLTPET/CT may not be competent for evaluation of distant metastasis from gastric cancer. The clinical utility of FLT-PET/CT may lie in monitoring therapeutic response and predicting prognosis. There is one pilot study which investigated the value of FLT-PET imaging in predicting gastric cancer response to neoadjuvant chemotherapy and prognosis [34]. In that study, FLTSUVmax, but not FDG-SUVmax at two weeks after chemotherapy was the only independent prognostic factor for gastric cancer patients. FLT-PET is also reported to be superior to FDG-PET in predicting breast cancer [35], head and neck cancer [36] and high-grade lymphoma [37] in assessing early response to therapy. The study limitation includes relatively small sample size because the main purpose of this study was to clarify the diagnostic performance of FLT- PET/CT for nodal staging compared with that of FDG-PET/CT based on pathological results. However, the power analysis supported the validity of the sample size about nodal metastasis in this study. In conclusion, FLT-PET/CT may have the same diagnostic value as FDG-PET/CT for detection of primary and nodal lesions of gastric cancer. Compliance with ethical standards Conflict of Interest The authors declare that they have no conflict interest. Animal rights statements This article does not contain any studies with animals performed by any of the authors. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individuals participants included in the study.

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