In our study, histopathological analysis following PET scan demonstrated tumor recurrence or metastasis in 27 of 39 patients who have normal CEA but clinically and/or radiologically suspicious tumor recurrence. Twelve patients were tumor free. PET was true positive in 22 patients and true negative in eight patients. The accuracy of PET was 76.9%. Our results demonstrated that PET was most accurate for liver metastases with a positive predictive value 88.8%. For local recurrence, PET had PPV of 73.3%. PET was false negative in five patients. In three of these patients pathology was consistent with mucinous carcinoma with signet cells. Consistent with our findings, it has been reported that the sensitivity of FDG-PET imaging for detection of mucinous carcinoma is significantly lower than in nonmucinous carcinoma (58% and 92%, respectively) [8]. PET was false positive in four patients. False positive PET lesions were mainly in the bowel and were secondary to infectious or inflammatory/granulomatous processes. False-positive findings with FDG-PET in colorectal region are not uncommon [32]. Increased FDG uptake is observed at recent incision and biopsy sites, around drainage tubes and catheters, and at colostomy sites, as well as in association with colitis, abscesses, fistulas, diverticulitis, and in some benign adenomas. This is because of increased glucose use in activated macrophages, neutrophils, and fibroblasts within infectious, inflammatory, and granulomatous tissues. Normal FDG uptake in the gastrointestinal tract may also cause difficulty to differentiate normal physiologic uptake from recurrent tumor.

There are many factors affecting the serum concentration of CEA, including tumor location, proximity to large vessels, degree of de-differentiation, access to portal circulation, tumor distribution, and tumor burden. Previously Moertel et al reported the inadequacy of CEA for early detection of tumor recurrence [23]. Only 25% of the patients had abnormal CEA levels although most patients had symptoms of recurrence for several months in their study. In two of our patients, CEA became positive 2 months after PET scan, suggesting that PET can show tumor recurrence earlier than CEA elevation. In our study, the lesion size was measured in focal solitary liver metastases in six patients. The tumor size ranged from 10 mm to 30 mm. However, our data is not sufficient to find the smallest tumor volume where PET can be positive while CEA negative. There are also many other factors in addition to tumor size affecting CEA level. However, we assume that given directly imaging the tumor and high glucose metabolism in tumor tissue, as well as current high-resolution PET/CT cameras, it is expected that FDGPET may detect tumor recurrence before significant increase in CEA level.

Although PET facilitates the evaluation of metabolic characteristics of tumors, it is limited in its ability to visualize anatomical structures. A PET/CT camera is the combination of PET and CT cameras which allows more accurate registration of metabolic findings in tumor with anatomical findings, adding further information to the diagnosis and staging of tumors. In PET/CT cameras, CT is also used for attenuation correction of PET images which significantly reduces imaging time. In our study, the accuracy of PET/CT was found to be lower than PET alone. However, given the smaller number of exams performed by PET/CT than by PET alone, this determination of accuracy may not reliably reflect the actual accuracy of PET/CT versus PET alone.

Our study had several potential limitations. The first potential limitation was our small sample size which may have limited the robustness of our study in terms of statistics. The second potential limitation was the retrospective nature of our study. Because of its retrospective nature, we were unable to obtain baseline clinical and laboratory data in some of the patients. The third potential limitation was the pooled nature of the PET and PET/CT data, given that different attenuation correction algorithms were used in these two imaging methods. However, this issue would be of more concern had we compared PET SUVmax to PET/CT SUVmax in the same given patient. In defense of this third potential limitation, there is recently published study pooling PET and PET/CT SUV results [33]. The fourth potential limitation was our inability to use oral contrast for the combined PET/CT studies, since some data is available which demonstrates that low density oral contrast administration during combined PET/CT studies further increases accuracy.

Conclusion

Although PET is commonly used to localize tumor recurrence in cases with elevated CEA, our results indicate that PET is also valuable to detect tumor recurrence in selected cases who have normal CEA but clinically and/or radiologically suspicious tumor recurrence. The PPV of PET is high, particularly in detecting liver metastases. While PET may not be practical for routine surveillance for all patients with CRC, it should be utilized in select cases where CEA is not reliable, such as tumors known to not secrete CEA. PET should also be utilized at the first sign of suspected recurrence to determine the extent of disease.

Competing interests
The author(s) declare that they have no competing interests.

Authors' contributions
IS designed the current study and collected the data. She organized, wrote, and revised the manuscript. MB was also involved in study design and the data collection. He performed the analyses of all the data. He assisted in the organization, writing, and editing of all aspects of this manuscript. SPP, NCH, and MVK assisted in the writing and editing of all aspects of this manuscript. EWM was the supervising senior physician for the entire project and assisted in the writing and editing of all aspects of this manuscript. All the authors have approved the final version of this manuscript.

Acknowledgements

Preliminary data from this paper were previously presented as a poster (poster number 1648) in the Scientific Poster Session at the 54th Annual Meeting of the Society of Nuclear Medicine (SNM) on June 5, 2007 in Washington, DC.