In all patients with negative PET and negative pathology results, follow-up CEA values were available. In six of these patients, follow-up CEA values were normal (mean follow-up time 18.8 months, range: 4–41 months). In two patients, follow-up CEA level increased (mean follow-up time 3 months, range: 2–6 months).

PET and PET/CT results were evaluated separately. PET was true positive in 16 patients, false negative in three patients, and true negative in eight patients. PET/CT was true positive in six patients, false positive in four patients, and false negative in two patients. There was no false positive result with PET and no true negative result with PET/ CT. The accuracy of PET and PET/CT was 88.8% and 50%, respectively. Mean ± SD of SUVmax of true positive and false positive lesions are shown in Table 3. The mean SUVmax in all true positive lesions tended to be lower than in all false positive lesions, though this did not reach statistical significance (5.51 ± 2.73 vs. 6.75 ± 5.1, p = 0.58). False positive PET findings associated with bowel showed a trend towards higher SUVmax compared to true positive lesions, but this was not statistically significant (8.5 ± 5.5 vs. 6.06 ± 3.5, p = 0.45).

Discussion

Approximately 70% of patients with newly diagnosed CRC are suitable for a curative resection, but up to 50% of patients recurrence develops usually within two years of surgery [12-14]. Ten to 50% of local recurrences may be suitable for surgical resection [12-20]. In patients with liver metastasis hepatic resection in properly selected patients offers up to a 30% chance of cure [21]. Early detection and prompt treatment of recurrence improves survival. Although CEA is used frequently in the postoperative follow-up period, its sensitivity for early detection of CRC recurrence is less than desirable [22]. Moertel et al. reported that CEA has a sensitivity of 59% in the detection of CRC recurrence [23]. CEA is also not specific for colorectal cancer. A wide variety of non-neoplastic conditions, such as smoking and liver and gastrointestinal diseases, may cause elevation in CEA. The use of PET as part of the diagnostic work-up of patients with rising CEA is well defined. However, there is a paucity of data concerning its role in patients with suspected CRC recurrence and normal CEA. We have shown that PET can be reliably applied in such patients to allow for earlier detection and management of recurrent CRC.

PET is a functional/metabolic imaging technique which has been widely used in the diagnosis, staging, and management of a wide variety of tumors. The most commonly used PET agent in oncology is 18F FDG, a positron-labeled non-physiologic analog of glucose. Malignant tumors avidly accumulate FDG because of accelerated glucose metabolism and increased rate of glucose transport and utilization in malignant cells. FDG in the blood is transported into the cells via glucose transporters and phosphorylated to FDG-6-phosphate by hexokinase. This is thought to occur more readily in tumors due to overexpression of the glucose transporters GLUT1 and GLUT3 and higher levels of hexokinase in malignant cells [24]. Because Glucose-6-phosphatase enzyme is low in most of the tissues and tumors, FDG-6-phosphate cannot be dephosphorylated to FDG. Therefore, FDG-6-phosphate cannot cross the cell membrane and is trapped in the cell. As well, FDG-6-phosphate cannot be utilized in the metabolic steps of glycolysis resulting in accumulation of the radioactive tracer.

Many studies have demonstrated that FDG-PET has high sensitivity and specificity in the detection of tumor recurrence in patients with rising tumor markers in the absence of a known source by anatomical imaging methods [2-5]. A meta-analysis determined the overall sensitivity of 97% and specificity of 76% for FDG PET for detecting recurrent CRC [25]. Studies have also demonstrated that FDG PET is more sensitive than CT for the detection of recurrent CRC [6-11]. PET was found to be superior to CT in the differentiation of fibrotic scar tissues from locally recurrent tumor [26]. The accuracy of PET for locally recurrent disease was reported as 95% which was superior to pelvic-CT (65%) [27]. PET is more sensitive than CT in detecting liver metastases and defining the number of the lobes involved. Arulapalam et al. reported the sensitivity of PET and CT as 100% and 45%, respectively, in the detection of liver metastasis [6]. Similar to CT, MRI also has limitations in the differentiation of fibrotic scar from local recurrence. Although there is increasing use of dynamic contrast-enhanced MR, it is not clear yet whether it is superior to PET in the detection of recurrence. Contrastenhanced liver MRI and whole-body FDG-PET were comparable in the detection of patients with liver metastases [28]. PET provided additional information about extrahepatic disease. PET is a valuable imaging method to differentiate isolated resectable recurrence from disseminated metastatic disease to select patients who would benefit from surgery [29]. Studies have also compared PET and PET/CT in the detection of CRC recurrence. The sensitivity, specificity and overall accuracy of PET were 80%, 69%, and 75%, respectively, compared with 89%, 92%, and 90%, respectively, for PET/CT [30]. Another study demonstrated superiority of PET/CT over PET in differentiating malignant from benign lesions and physiologic activities [31]. The most common cause for false-positive interpretation of PET findings was physiologic FDG uptake in pelvic organs.