Background
Colorectal cancer (CRC) is the third most common cause of cancer in both men and in women in the United States. The five-year overall survival rates is 64% [1]. Local recurrence rate is relatively high despite radical curative surgery and up to 50% of patients with local recurrence may benefit from surgery.

Early detection and treatment of tumor recurrence is the only hope for long-term survival. Although carcinoembryonic antigen (CEA) is the most frequently used tumor marker, it has low sensitivity in the early detection of recurrent colorectal cancer (CRC). Conventional imaging methods such as Computed Tomography (CT) and Magnetic Resonance Imaging (MR) have limited value in differentiating post-surgical changes from local tumor recurrence. Positron Emission Tomography (PET) and, particularly, Positron Emission Tomography/Computed Tomography (PET/CT) are widely accepted imaging methods in the management of a wide variety of cancers, including CRC. Many studies have demonstrated the value of PET in the detection of CRC recurrence in patients with rising CEA in the post-operative period [2-5]. Studies have also demonstrated the superiority of PET over CT in the detection of local CRC recurrence as well as metastatic disease [6-11]. The role of PET in patients with normal CEA levels, however, is not clear.

In this study, we aimed to analyze the value of FDG-PET scans in patients with normal CEA levels but clinical or radiological findings suspicious for tumor recurrence.

Methods

A retrospective review of our electronic database of 308 patients with CRC imaged by PET or PET/CT between January 2003 and December 2005 was performed to select and analyze PET scan findings of patients who had normal CEA but clinically and/or radiologically suspicious findings for tumor recurrence. Only patients with correlative histopathological data were included. The institutional review board allowed an exempt retrospective review of the cancer PET database, and informed consent was waived. The normal range for CEA in our clinical laboratory was 0–5.0 ng/mL (chemiluminescent immunoassay). Although the CEA levels were available and normal on all patients at the time of their evaluation for suspicion of recurrent CRC, initial baseline CEA levels taken at a time before their initial treatment for their originally diagnosed CRC were available in only 10 patients (with initial baseline CEA level within normal range in seven patients and elevated in three patients).

PET studies were performed on Siemens Biograph 16 PET/ CT and HR plus Siemens CTI PET camera (CTI, Inc, Knoxville, TN). The patients fasted approximately 6 hours prior to intravenous injection of 370–555 MBq (10–15 mCi) of Fluorine 18-fluoro-2-deoxy-glucose (18F FDG). Blood glucose levels were checked prior to the injection of 18F FDG. Studies were performed only when blood glucose levels did not exceed 150 mg/dL. The imaging started approximately 60 minutes following intravenous injection of 18F FDG. For the PET/CT camera, first a scout view was obtained with 30 mAs and 130 kVp followed by a spiral CT scan with 130 mAs, 130 kVp, 5-mm scan width, and 12-mm feed per rotation without any specific breathholding instructions. No IV or oral contrast was given to the patients for acquisition of the CT images. Imaging area was from skull base to proximal femora. PET scanning was performed immediately after acquisition of the CT images without changing the patient position with 2–4 minutes per bed acquisition time. PET images were corrected for attenuation on the basis of the CT data, and iterative reconstruction algorithms were used for reconstruction. For the PET only camera, image acquisition time of 10 minutes per bed by using 40% transmission and 60% emission protocol was used. PET images were corrected for attenuation on the basis of the transmission image data, and iterative reconstruction algorithms were used for reconstruction. PET images were evaluated by two boardcertified nuclear medicine physicians (IS and NCH). PET scan was considered positive or suspicious when abnormal non-physiologic metabolic activity was identified. Focal hypermetabolic activity within the liver greater than adjacent normal liver was considered abnormal. Isometabolic liver lesions (metabolic activity equal to liver) were only identified with the help of CT in patients with PET/ CT scan. Diffuse mild activity in the bowel was considered normal physiologic uptake. Quantification of the tumor metabolic activity was obtained using the Standardized Uptake Value (SUV) normalized to body weight. Mean ± SD of maximum-pixel SUV (SUVmax) of the lesions were calculated. The significance of SUVmax between false positive and true positive lesions were compared by t-test. A Pvalue of less than or equal to 0.05 was considered statistically significant.

Results

A total of 369 PET studies (PET: 183, from January 2003 to March 2005 and combined PET/CT: 186, from April 2005 to December 2006) in 308 patients with CRC were reviewed. Only patients with clinical and/or radiological suspicion of tumor recurrence but normal CEA who have histopathological evaluation following PET scan were selected for further analysis. Thirty-nine patients met the inclusion criteria. The PET studies were performed by PET scan alone in 27 patients and by combined PET/CT scan in 12 patients. PET was ordered in these patients because of suspicious or equivocal lesions on CT in 17, on barium study in two, or on history and physical exam in 20. The characteristics of the patients are summarized in Table 1.