PET/CT findings in gastric cancer: potential advantages and current limitations

Saadet Atay-Rosenthal^*, Richard L Wahl & Elliot K Fishman

The Russell H. Morgan Department of Radiology & Radiological Sciences, Johns Hopkins Hospital, 601 N. Caroline Street, Johns Hopkins Outpatient Center, Office 3171D, Baltimore, MD 21287, USA

Corresponding Author:

Saadet Atay-Rosenthal
The Russell H. Morgan Department of Radiology & Radiological Sciences
Johns Hopkins Hospital, 601 N. Caroline Street
Johns Hopkins Outpatient Center, Office 3171D, Baltimore, MD 21287, USA
Tel: +1 410 502 8052
Fax: +1 443 287 6422
E-mail: satayro1@jhmi.edu

Abstract

18F-fluorodeoxyglucose (18F-FDG) as a substrate for tumors with high glucose metabolism has been the most commonly used 18F-FDG-PET radiopharmaceutical in oncologic imaging. However, the usefulness of 18F-FDG-PET in gastric cancer has not yet been fully established. The intent of this review is to help to better understand the impact of 18F‑FDG-PET on the imaging of gastric cancer, to offer a greater understanding of how gastric malignancies may present and be recognized on 18F‑FDG‑PET and to assess the complementary value of PET/CT in gastric cancer staging.

Keywords

¹⁸F-FDG-PET ▪ ¹⁸F-fluorodeoxyglucose ▪ gastric cancer staging ▪ gastric carcinoma ▪ PET/CT ▪ TNM staging

Successful management of gastric cancer depends on early detection and accurate staging of disease as surgery is the only curative treatment method for localized disease. Endoscopic ultrasound has been the most reliable nonsurgical method in evaluation of the primary tumor, however, recent studies comparing the preoperative staging of gastric cancer by endoscopic ultrasound with multidetector CT show that the two modalities demonstrate very close accuracy in determining the individual T and N stage [1,2]. Multidetector CT is currently the staging modality of choice in identifying the primary tumor, assessing the local spread of the tumor, detecting local and distant nodal disease and metastasis [3–5]. Considering that on average 25% of patients with newly diagnosed gastric carcinoma have undetectable intra-abdominal M1 disease (metastasis to peritoneum, liver or nonregional lymph nodes) by current imaging modalities and yet detected at surgical staging [6], there is a need for better imaging to evaluate the extent of disease and avoid unnecessary surgery.

The role of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)- PET in detection of primary gastric cancer and lymph node metastasis has been controversial. There is limited data on use of PET/CT for preoperative staging of gastric cancer, although there is growing interest in this topic [7]. ¹⁸F-FDGPET can be useful in postoperative follow-up of gastric cancer patients with suspected recurrent gastric cancer, especially when the recurrence is suspected clinically because of its high positive predictive value [8,9]. Treatment decisions were changed in 30.4% patients when PET/CT was introduced to conventional follow-up [10]. Significant correlation was found between ¹⁸F-FDG-PET uptake and patient survival [11].

In this article we review some of the gastric ¹⁸F-FDG uptake patterns and their importance in gastric cancer detection, and describe the additional value of PET/CT on gastric cancer staging illustrated with case examples. The studies were performed in routine setting with dedicated PET/CT system with no special preparation in terms of gastric distention other than oral contrast or water on the table before imaging.

Gastric ¹⁸F-FDG-uptake pattern & significance

Variable physiologic ¹⁸F-FDG uptake simply caused by visceral thickening, physiological emptying, or inflammatory disease in the alimentary tract often makes it difficult to differentiate normal uptake from pathology. Highly variable normal gastric ¹⁸F-FDG uptake limits the PET detection rate for early gastric cancer. Only 60% of locally advanced gastric carcinoma was detected by ¹⁸F-FDG-PET in a report by Stahl et al. [12].

There is high patient-to-patient variation in the concentration of tracer at the gastroesophageal junction (GEJ) and gastric antrum [13]. However, a specific pattern of gastric ¹⁸F-FDG uptake was demonstrated by Koga et al. in a review of 22 patients without any gastric lesions. The gastric regions were classified into U (upper)- area, M (middle)-area and L (lower)-area. In all cases, the ¹⁸F-FDG uptake in the U-area was equal to or higher than in the M- and L-areas (U > M > L) [14]. Thus, higher focal uptake in the M- or L-area compared with the upper area may be suggestive of pathologic uptake (Figures 1–3).

Kamimura et al. in a prospective evaluation of 60 patients, however, did not find a significant difference in each gastric area when an additional 400 ml of water was given prior to imaging. The standardized uptake value (SUV) remains high, however, in the GEJ than in the U-area [15].

The physiological gastric uptake can be somewhat reduced in some instances using gastric distention. The potential importance of additional water intake or vesicant just before the study to differentiate physiological from pathological uptake in primary and recurrent tumors has been demonstrated in several articles [15–19]. Gastric distention enabled better delineation of the lesions and reduction in nonspecific uptake. Kamimura et al. reported increased specificity from 50 to 100% and negative predictive value from 72 to 94% in patients with locally advanced gastric carcinomas after ingestion of 400 ml of water and additional spot imaging of the stomach. The average SUV of the stomach declined from 2.6 to 1.65 following gastric distention (SUV units are g/ml, however in the following discussion we adopt conventional practice and present SUV in dimensionless units) [18].

Histological types of gastric cancer can cause significant variation in ¹⁸F-FDG uptake. Moderately differentiated type tubular adenocarcinoma and intestinal type of advanced gastric cancer reveal significantly higher uptake (SUV: 7.7–13.2). Nonintestinal diffuse type, mucinous adenocarcinoma and carcinomas containing signet ring cells display low detectability on PET. This is, in part, due to high content of metabolically quite inert mucus and low tumor cell density. One other reason may be lack of expression of the glucose transporter Glut-1 on the cell membrane of most signet ring cells and mucinous adenocarcinoma [20–23]. Both the depth of tumor invasion and histological subtypes were found to be independent factors influencing the ¹⁸F-FDG avidity. Glut-1 expression was the most influential factor for the degree of ¹⁸F-FDG uptake in gastric cancer in multiple regression analysis (p < 0.01) [24]. In nonintestinal type gastric cancer with a high number of signet ring cells, thymidine analog 3´-deoxy-3´-¹⁸F-fluorothymidine (FLT) PET may be used for imaging, which has shown 100% sensitivity compared with 69% with ¹⁸F-FDG-PET in locally advanced gastric cancer in a pilot study of 45 patients [25]. In 21 patients with newly diagnosed advanced gastric cancer the sensitivities of FLT-PET and ¹⁸F-FDG-PET were 95.2 and 95%, respectively. The FLT-PET signal is often quite low, however [26].

We demonstrate a case of signet ring carcinoma with moderately positive ¹⁸F-FDG uptake (Figures 4 & 5).

The site of primary tumor may also influence the detection rate by ¹⁸F-FDG-PET such that proximal lesions are detected at a higher rate; however, the results are controversial [22,23].

One of the larger series is by Takahashi et al. studying the significance of gastric ¹⁸F-FDG accumulation in a retrospective analysis of 599 patients. The main cause for nonspecific accumulation was inf lammatory mucosal changes forming a background for the development of cancer or malignant lymphoma. In this study although the ¹⁸F-FDG uptake was thought to be nonspecific in four out of 91 positive cases, endoscopy revealed three cases of early gastric cancer and one case of mucosa-associated lymphoid tissue lymphoma. Two of the early gastric cancers were signet ring type with the lesion sizes of 5 and 14 mm. Incidental lesions also included benign disorders, such as gastric and duodenal ulcer and gastric submucosal tumor [27].

SUV & its implications

¹⁸F-FDG uptake in the tumor is semiquantitatively assessed using SUV. SUVs are dependent on many parameters including, but not limited to, time after ¹⁸F-FDG injection, tumor size and blood glucose level and are also affected by the methods of both image reconstruction and attenuation correction. Although there is no consensus on the cutoff level, 95% of patients with disease-free stomach demonstrate a peak SUV of less than four in the GEJ and gastric antrum [13].

SUV values are important in estimating prognosis and follow-up of patients. Significant correlation is observed between SUV and the primary size of tumors. The gastric cancers with high ¹⁸F-FDG uptake tend to have higher malignant aggressiveness as there is significant correlation between the primary tumor SUV and lymph node metastases [20]. High ¹⁸F-FDG uptake in primary tumors increases the accuracy of FDG-PET assessment of lymph node stage [28]. Patients with high tumor SUV had poorer prognosis with lower survival rates than those with low SUVs [23].

Serial ¹⁸F-FDG-PET imaging is used to monitor cytotoxic therapy and for early prediction of histopathological response to chemotherapy. In a study by Stahl et al., relative tumor SUV changes were not influenced by any of the methodological variations, such as time delay, after ¹⁸F-FDG injection, acquisition protocol, reconstruction algorithm or normalization of SUV, as long as they were the same method for pre- and post-treatment imaging, in a retrospective evaluation of 43 patients with serial imaging. When a decline in tumor SUV of approximately 40% was used as a cutoff value between responders and nonresponders, the accuracy for prediction of response was high at 80% [29]. Similar results were obtained in other studies assessing the relative changes in tumor ¹⁸F-FDG uptake for prediction of outcome as early as 2 weeks after initiation of therapy [30,31].

The therapy induced reduction of ¹⁸F-FDG-PET predicted early metabolic response according to RECIST, in patients with advanced gastric adenocarcinoma treated with chemotherapy plus cetuximab at 6 weeks with

Patients with a significant histopathological response to preoperative therapy also have better prognosis and higher survival rates. The 2-year survival was 87% compared with 44% in nonresponders (p = 0.02) in a study by Wieder et al. in patients with locally advanced adenocarcinoma of the esophagogastric junction [30].

When a tumor is partially treated, whether by chemotherapy or radiation, its maximum SUV can frequently be below four yet harbor significant residual disease (Figure 6).

Staging

■ Detection of primary tumors: T-staging

The sensitivity rate for detecting primary gastric tumors by ¹⁸F-FDG-PET alone ranges between 58 and 94% among studies (median 81.5%); the specificity, however, ranges from 78 to 100% (median 100%) [21]. The detection rate is even lower for early stage gastric cancers. In early gastric cancer (EGC), only the intestinal type was detectable with ¹⁸F-FDG-PET [33]. Advancedstage gastric cancer is detected by PET imaging in 90% of patients as opposed to 40% in early stage gastric cancers [23].

The screening sensitivity of ¹⁸F-FDG with PET-only imaging was found to be even lower (12.5%) in an asymptomatic patient group of 2861 subjects when endoscopy (chromoendoscopy with enhanced ability to detect small lesions) findings were used as a gold standard. The study, however, reveals high specificity and negative predictive values of 99.2 and 99.4%, respectively [34].

¹⁸F-FDG-PET improves TNM staging. In a prospective study by Chen et al. a high sensitivity of 94% was found when 68 patients with biopsy proven early and advanced gastric cancer were enrolled for preoperative staging [20].

Yun et al. reported that ¹⁸F-FDG-PET is as accurate as CT for detecting primary tumors of the stomach in either EGC or advanced gastric cancer [35].

Limited data are available on combined PET/CT that would further improve the diagnostic performance. In a recent article, Kim et al. showed high sensitivity of PET/CT for the detection of primary tumors (n = 66 out of 71; 93%), similar to the detection rate for contrast-enhanced CT (n = 64 out of 71, 90%; p = 0.55) [7].

■ Detection of regional lymph node metastases: N-staging

Lymph node status is an important prognostic factor regarding long-term survival [36]. The extent of lymph node metastasis at primary diagnosis is the most important independent factor associated with the survival time and determining the timing of tumor recurrence [21,37].

CT has major limitations detecting cancerous involvement of normal-sized lymph nodes and cannot differentiate between reactive hyperplasia and metastatic enlargement. Regional lymph nodes are considered to represent local metastasis if they are solitary or separate nodes of 8 mm or greater in the long axis diameter, round shape, or exhibiting central necrosis with marked or heterogeneous enhancement [36,38]. However, in the literature 55% of the metastatic lymph nodes are found to be 5 mm or less in diameter. When 348 lymph nodes less than 3 mm were analyzed prospectively in 31 gastrectomy specimens, 14.5% were found to have metastasis in histological evaluation [36].

¹⁸F-FDG-PET has limited detection of locoregional lymph node metastases from gastric cancer [39]. Perigastric lymph nodes may not be distinguished from the primary tumor or the normal stomach wall. The sensitivity of CT for N1 disease was found to be significantly higher than that of PET. However, the sensitivity, specificity and accuracy of ¹⁸F-FDG-PET were not significantly different from CT for primary tumors or for N2 and N3 metastases in EGC and advanced gastric cancer. In clinical practice, detection of N2 or N3 disease status may change the extent of lymphadenectomy. In advanced gastric cancer, all patients undergo D1 dissection anyway so detection of N1 status may not change the treatment [35].

During the evaluation of lymph node staging ¹⁸F-FDG-PET shows 23.3% sensitivity and 100% specificity whereas CT shows 65% sensitivity and 77% specificity in a study of 85 patients when the lymph node was considered positive if the long axis diameter was more than 1 cm [23]. Kim et al. reported that according to multiple logistic regression analysis the SUV of the primary tumors was the only independent variable to be significantly related to sensitivity for lymph node metastases [28].

Current ¹⁸F-FDG-PET scanners have 4–10 mm spatial resolution, which may also explain the low sensitivity especially in detection of perigastric N1 lymph nodes. PET/CT fusion provides both anatomic and functional information and improves localization of foci with increased uptake than standalone PET (Figures 7 & 8). The tumor detection task is complicated by small size, low uptake in tumors and high normal ¹⁸F-FDG background uptake.

The sensitivity and accuracy of PET/CT was found to be inferior to contrast-enhanced CT, however, specificity and positive predictive value for PET/CT was significantly higher than for CT in a series of 59 patients with confirmed regional lymph node metastases [7].

■ Detection of distant metastases: M-staging

Detection of metastatic lymph nodes is found to be particularly poor with PET with a sensitivity of only 20.6% [23]. Both ¹⁸F-FDG-PET and CT have low sensitivity in detecting N2 and N3 lymph node stations between 33–46.2 and 44–63.1%, respectively. The ¹⁸F-FDG-PET specificity on the other hand ranges between 91 and 100% (median: 96%) for N1 and N2 stations.

The sensitivity of ¹⁸F-FDG-PET with regard to lymph node metastases increases to 65% with a 90% specificity in cases with high primary tumor SUV. Signet ring cell carcinoma reveals the lowest sensitivity (15%), whereas other cell types can be detected with moderate sensitivity (30–71%) [28].

¹⁸F-FDG-PET has a better positive predictive value for lymph node metastases compared with CT, which affects treatment strategy in considering palliative therapy. When there is involvement of N3 lymph nodes a palliative approach is considered rather than curative resection [21].

Kim et al. demonstrate that in a series of 11 patients with distant metastases all of the four distant lymph node metastases were detected by combined PET/CT and one was missed by CT alone owing to small size [7]. PET/CT would be particularly important in distant metastases detection.

PET has very limited value in detecting peritoneal carcinomatosis with a low sensitivity (range: 9–50%; median: 32.5%), but relatively higher specificity of (63–99%; median: 88.5%). Low sensitivity may be explained by associated fibrosis, small size of peritoneal lesions (<5 mm) and low number of tumor cells in ascites, pleural and bone metastases [21].

Limited sensitivity for detecting peritoneal carcinomatosis with ¹⁸F-FDG-PET or CT scanning alone (57 and 43%, respectively) has been reported. When the images were evaluated together the sensitivity increased to 78% with a high positive predictive value of 95% in a study by Turlakow et al. [40]. The sensitivity and specificity of PET/CT was found to be similar to contrast-enhanced CT in all sites of recurrence in a study by Sim et al. except peritoneal seeding in which contrast-enhanced CT was more sensitive [41].

Evaluation of distant metastasis by PET alone is limited with reported sensitivity and specificity of 85 and 74% in detection of liver metastasis; 67 and 88% for lung metastases; 24 and 76% for ascites; 4 and 100% for pleural carcinomatosis; and 30 and 82% for bone metastases, respectively [21]. The results are better with a dedicated PET/CT system with a per-lesionbased positive predictive value of up to 89% in detecting recurrence after surgical resection. A study by Park et al. demonstrated that among the 108 recurrence sites, lymph node and lung metastases showed a higher rate of ¹⁸F-FDG uptake while nearly half of bowel metastases showed negative uptake and all uptake in lymph nodes and bones were true positive [8].

Combined imaging with the higher sensitivity of CT and higher specificity of PET will be more helpful in these cases than either imaging alone (Figure 9).

Conclusion

¹⁸F-FDG-PET alone has a limited role in detecting and evaluating the local extent of primary gastric cancer with a low detection rate of early gastric cancer and variable uptake depending on histological subtype. PET/CT has a better positive predictive value for lymph node metastasis compared with CT alone, with reasonable sensitivity for liver and lung metastasis. ¹⁸F-FDG-PET provides valuable information on tumor aggressiveness and estimation of prognosis. The combination of PET/ CT overcoming the limitations of either modality alone and improving the system resolution will be more valuable in preoperative staging of gastric cancer, especially in evaluation of distant metastases.

Future perspective

PET/CT imaging in gastric cancer, with increased accuracy in preoperative staging precluding unnecessary surgery and increased sensitivity for detection of recurrence in postoperative follow-up of patients, will be utilized more in the future in the correct clinical setting.

Prediction of early response to therapy for ¹⁸F-FDG-avid tumors, which helps to estimate prognosis and survival rates, will help to monitor individualized therapy, preventing unnecessary prolonged chemotherapy and therapy-related toxicity.

Clinical utility of PET/CT will increase if the patient population is selected carefully. The selection parameters would depend on histopathological subtype (intestinal vs nonintestinal); stage (early vs advanced gastric cancer); and according to the baseline ¹⁸F-FDG tumor uptake (high vs low), which would increase the test sensitivity in detection rate of metastasis and prediction of therapy response.

Depending on histopathological subtype of tumor, new tracers such as FLT-PET and possibly new tracers and metabolic agents being developed may play a role to further increase PET usage. We still need better tracers for gastric cancer.

The clinical utility of PET/CT will further increase with application of better techniques such as good gastric distention and with future developments in dedicated PET/CT imaging systems with higher spatial resolution and faster imaging.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

References

Papers of special note have been highlighted as:

• • of considerable interest

1. Haberman CR, Weiss F, Riecken R et al. Preoperative staging of gastric adenocarcinoma: comparison of helical CT and endoscopic US. Radiology 230, 465–471 (2004).
2. Hwang SW, Lee DH, Lee SH et al. Preoperative staging of gastric cancer by endoscopic ultrasonography and multidetectorrow computed tomography. J. Gastroenterol. Hepatol. 25(3), 512–518 (2010).
3. Horton KM, Fishman EK. Current role of CT in imaging of the stomach. Radiographics 23, 75–87 (2003).

• • Good overview of multidetector CT technique and applications on gastric imaging.

4. Gore RM. Upper gastrointestinal tract tumors: diagnosis and treating strategies. Cancer Imaging 5, 95–98 (2005).
5. Kim HJ, Kim AY, Oh ST et al. Gastric cancer staging at multi-detector row CT gastrography: comparison of transverse and volumetric CT scanning. Radiology 236, 879–885 (2005).
6. Sarela AI, Miner TJ, Karpeh MS et al. Clinical outcomes with laparoscopic stage M1, unresected gastric adenocarcinoma. Ann. Surg. 243, 189–195 (2006).
7. Kim EY, Lee WJ, Choi D et al. The value of PET-CT for preoperative staging of advanced gastric cancer: comparison with contrastenhanced CT. Eur. J. Radiol. 79, 183–188 (2011).

• • One of the earliest papers on the use of PET/CT for preoperative staging of gastric cancer and in comparison to multidetector CT.

8. Park MJ, Lee WJ, Lim HK, Park KW, Choi JY, Kim BT. Detecting recurrence of gastric cancer: the value of FDG PET/CT. Abdom. Imaging 34, 441–447 (2009).

• • One of the early few studies on PET/CT in patients with suspected recurrent gastric cancer with a high positive predictive value.

9. Nakamoto Y, Togashi K, Kaneta T et al. Clinical value of whole body PET for recurrent gastric cancer: a multicenter study. Jap. J. Clin. Oncol. 39(5), 297–302 (2009).

• • Multicenter study on clinical usefulness of ¹⁸F-fluorodeoxyglucose‑PET in patients with suspected recurrent gastric cancer, demonstrating change in therapeutic management in up to 48% of the patients in a selected patient group.

10. Sun L, Su XH, Guan YS et al. Clinical role of ¹⁸F fluorodeoxyglucose positron emission tomography/computed tomography in post-operative follow up of gastric cancer: initial results. World J. Gastroenterol. 14(29), 4627–4632 (2008).
11. Potter TD, Flamen P, Cutsem V et al. Whole body PET with FDG for the diagnosis of recurrent gastric cancer. Eur. J. Nucl. Med. 29(4), 525–529 (2002).
12. Stahl A, Ott K, Weber WA et al. FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings. Eur. J. Nucl. Med. 30(2), 288–295 (2003).
13. Salaun PY, Grewal RK, Dodamane I et al. An analysis of the ¹⁸F-FDG uptake pattern in the stomach. J. Nucl. Med. 46, 48–51 (2005).
14. Koga H, Sasaki M, Kuwabara Y et al. An analysis of the physiological FDG uptake pattern in the stomach. Ann. Nucl. Med. 17(8), 733–738 (2003).
15. Kamimura K, Fujita S, Nishii R et al. An analysis of physiological FDG uptake in the stomach with the water gastric distention method. Eur. J. Nucl. Med. Mol. Imaging 34, 1815–1818 (2007).
16. Imperiale A, Cimarelli S, Sellem DB, Blondet C, Contantinesco A. Focal F-18 FDG uptake mimicking malignant gastric localizations disappearing after water ingestion on PET/CT images. Clin. Nucl. Med. 31(12), 835–837 (2006).
17. Tian J, Chen L, Wei B et al. The value of vesicant ¹⁸F-FDG PET in gastric malignancies. Nucl. Med. Commun. 25, 825–831 (2004).
18. Kamimura K, Nagamachi S, Wakamatsu H et al. Role of gastric distention with additional water in differentiating locally advanced gastric carcinomas from physiological uptake in the stomach on ¹⁸F-fluoro-2-deoxy-dglucose PET. Nucl. Med. Commun. 30, 431–439 (2009).

• • Valuable information is provided improving the detection rate with additional water and regional imaging with increased specificity, positive predictive value and accuracy.

19. Yun M, Choi HS, Yoo E, Bong JK, Ryu YH, Lee JD. The role of gastric distention in differentiating recurrent tumor from physiological uptake in the remnant stomach on ¹⁸F-FDG PET. J. Nucl. Med. 46, 953–957 (2005).
20. Chen J, Cheong JH, Yun MJ et al. Improvement in preoperative staging of gastric adenocarcinoma with positron emission tomography. Cancer 103, 2383– 2390 (2005).
21. Dassen AE, Lips DJ, Hoekstra CJ et al. FDGPET has no definite role in preoperative imaging in gastric cancer. Eur. J. Surg. Oncol. 35, 449–455 (2009).
22. Yoshioka T, Yamaguchi K, Kubota K et al. Evaluation of F18-FDG PET in patients with advanced, metastatic, or recurrent gastric cancer. J. Nucl. Med. 44, 690–699 (2003).
23. Mochiki E, Kuwano H, Katoh H, Asao T, Oriuchi N, Endo K. Evaluation of ¹⁸F-2- deoxy-2-fluoro-d-glucose positron emission tomography for gastric cancer. World J. Surg. 28, 247–253 (2004).
24. Yamada A, Oguchi K, Fukushima M, Imai Y, Kadoya M. Evaluation of 2-deoxy-2-¹⁸F fluoro-d-glucose positron emission tomography in gastric carcinoma: relation to histological subtypes, depth of tumor invasion, and glucose transporter-1 expression. Ann. Nucl. Med. 20, 597–604 (2006).
25. Herrmann K, Ott K, Buck AK et al. Imaging gastric cancer with PET and the radiotracers ¹⁸F-FLT and ¹⁸F-FDG: a comparative analysis. J. Nucl. Med. 48, 1945–1950 (2007).
26. Kameyama R, Yamamato Y, Izuishi K et al. Detection of gastric cancer using ¹⁸F-FLT PET: comparison with ¹⁸F-FDG PET. Eur. J. Nucl. Med. Mol. Imaging 36, 382–388 (2009).
27. Takahashi H, Ukawa K, Ohkawa N et al. Significance of F18-2-deoxy-2-fluoro-glucose accumulation in the stomach on positron emission tomography. Ann. Nucl. Med. 23, 391–397 (2009).
28. Kim SK, Kang KW, Lee JS et al. Assessment of lymph node metastases using ¹⁸F-FDG PET in patients with advanced gastric cancer. Eur. J. Nucl. Med. Mol. Imaging 33, 148–155 (2006).
29. Stahl A, Ott K, Schwaiger M, Weber WA. Comparison of different SUV based methods for monitoring cytotoxic therapy with FDG PET. Eur. J. Nucl. Med. Mol. Imaging 31, 1471–1479 (2004).
30. Wieder HA, Ott K, Lordick F et al. Prediction of tumor response by FDG-PET: comparison of the accuracy of single and sequential studies in patients with adenocarcinoma of the esophagogastric junction. Eur. J. Nucl. Med. Mol. Imaging 34, 1925–1932 (2007).
31. Ott BK, Fink U, Becker K et al. Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J. Clin. Gastric Cancer 10, 221–227 (2007).
32. Di Fabio F, Pinto C, Rojas Llimpe FL et al. The predictive value of ¹⁸F-FDG-PET early evaluation in patients with metastatic gastric adenocarcinoma treated with chemotherapy plus cetuximab. Gastric Cancer 10(4), 221–227 (2007).
33. Mukai K, Ishida Y, Okajima K, Isozaki H, Morimoto T, Nishiyama S. Usefulness of preoperative FDG-PET for detection of gastric cancer. Gastric Cancer 9, 192–196 (2006).
34. Shoda H, Kakugawa Y, Saito D et al. Evaluation of ¹⁸F-2-deoxy-2-fluoro-glucose positron emission tomography for gastric cancer screening in asymptomatic individuals undergoing endoscopy. Br. J. Cancer 97, 1493–1498 (2007).
35. Yun M, Lim JS, Noh SH et al. Lymph node staging of gastric cancer using ¹⁸F-FDG PET: a comparison study with CT. J. Nucl. Med. 46, 1582–1588 (2005).
36. Kwee RM, Kwee TC. Imaging in assessing lymph node status in gastric cancer. Gastric Cancer 12, 6–22 (2009).
37. Shiraishi N, Inomata M, Osawa N, Yasuda K, Adachi Y, Kitano S. Early and late recurrence after gastrectomy for gastric carcinoma. Univariate and multivariate analyses. Cancer 89, 255–261 (2000).
38. Chen CY, Hsu JS, Wu DC et al. Gastric cancer: preoperative local staging with 3D multidetector row CT-correlation with surgical and histopathologic results. Radiology 242, 472–482 (2007).

• • Very good prospective study with combined virtual gastroscopy and dynamic contrastenhanced multiplanar reformations illustrated with very good cases and detailed teachings on preoperative gastric cancer imaging.

39. Lim JS, Yun MJ, Kim MJ et al. CT and PET in stomach cancer: preoperative staging and monitoring of response to therapy. Radiographics 26, 143–156 (2006).

• • Excellent overview on preoperative staging of gastric cancer and follow-up supported with excellent case examples.

40. Turlakow A, Yeung HW, Salmon AS, Macapinlac HA, Larson SM. Peritoneal carcinomatosis: role of ¹⁸F-FDG PET. J. Nucl. Med. 44, 1407–1412 (2003).
41. Sim SH, Kim YJ, Oh DY et al. The role of PET/CT in detection of gastric cancer recurrence. BMC Cancer 9, 73 (2009).