Positron emission tomography

PET refers to the acquisition of anatomic and metabolic data by a PET camera. The most commonly used radiotracer used for PET imaging is 18-F fluo-rodeoxyglucose (FDG). FDG is an analogue of glucose that is transported by glucose transporters and phosphorylated by hexokinase to FDG-6-phos-phate. The polar nature of FDG-6-phosphate reduces the capacity of the molecule to diffuse out of a cell and the stereochemistry of FDG is such that it is not a substrate for any further metabolism. The net effect is a quantifiable, objective measure of the rate of metabolism from the time of injection to the time of imaging. In general, cancer cells have an accelerated glucose metabolism [106]. Many of the pathophysiologic and cellular processes that lead to or result from inflammation are mimicked by oncogenesis. FDG imaging for cancer is rendered less specific because both inflammation and onco-genesis are associated with accelerated glucose metabolism. Newer agents are being investigated but need Food and Drug Administration approval.

One distinct advantage of PET imaging over anatomic imaging is that quantitative results are generated; this allows assessment and reassessment of locoregional metabolism before and after treatment (the hypothesis being that measurable alterations in FDG metabolism reflect the biologic processes induced by a treatment, before a structural change occurs). Reliable imaging with FDG requires consistency and use of strict practice guidelines to ensure dependability and reproducibility. A large amount of data is acquired and quantitative results are generated. Examples of good practice guidelines include injection of adequate amounts of radioactivity and imaging for a sufficient period of time to ensure images are of sufficient quality for interpretation and analysis. If semiquantitative measures of FDG uptake are to be used for patient follow-up, such as the standardized uptake value, the same measure (eg, maximum uptake within a region of interest versus average uptake) should be used. Consistency in postinjection image acquisition times for subsequent FDG PET scans is necessary to generate biologically relevant semiquantitative information; the same can be said for the use of the same camera with the same reconstruction algorithm. Strict adherence to institutional standards for patient elevated blood glucose (eg, >150 mg/mL) is recommended so that rescheduling of patients is done if proper levels do not exist.

FDG PET imaging has a role in the preoperative evaluation of patients with a biologically aggressive primary and in patients with suspected recurrence to exclude unexpected distant metastases. There is also a role of FDG PET in the work-up of patients with occult disease manifesting solely as an elevated CEA level. The early FDG PET literature was remarkably consistent across many tumor types whereby the addition of FDG imaging to conventional imaging led to management change in about one third of all cases. There have been significant changes in the technology of cross-sectional imaging devices in the last 10 years with the widespread implementation of multislice CT scanners and higher field strength MR imaging machines. The increment in PET acquisition technology has been comparatively small over the interim with modest changes in sensitivity and resolution of PET devices. It is likely that the clinical impact of the addition of PET data alone has lessened as the performance of other modalities has improved. The greatest innovation in PET imaging devices has not been the PET device itself but rather the successful deployment of PET-CT scanners that are fully integrated allowing generation of anatomically coregistered or fused images. Although difficult to quantify, it is generally accepted that anatomically coregistered imaging improves the interpretation of both the PET and CT data. A representative case in which a peritoneal lesion was missed on CT (Fig. 22A) reveals that it was detected on FDG fusion images (Fig. 22B). Finally, an important and emerging role exists for PET imaging in treatment monitoring.

A further extension of this is to use FDG PET imaging at an early time point in the course of treatment to determine if otherwise toxic therapy is resulting in an expected fall in glucose metabolism. This technique has been used in other tumor types and parameters associated with good outcomes have been described [107-109].

A classic indication for CRC imaging with FDG PET is CEA elevation with a negative CT examination. It has been shown that there is a correlation between metabolically active tumor bulk as measured by PET and CEA level [110]. As more and more CT scans are performed using multislice helical technology, the false-negative rate on CT

Fig. 22. (A) Axial contrast-enhanced CTscan showing a peritoneal implant (arrow) mimicking unfilled intestine. (B) PET-CT fusion image four-quadrant screen revealing coronal (upper left) and axial (upper right) PET, and un-fused CT (lower left) and fused PET-CT (lower right) with grid lines indicating FDG avid peritoneal implant missed on CT (see A).

Fig. 22. (A) Axial contrast-enhanced CTscan showing a peritoneal implant (arrow) mimicking unfilled intestine. (B) PET-CT fusion image four-quadrant screen revealing coronal (upper left) and axial (upper right) PET, and un-fused CT (lower left) and fused PET-CT (lower right) with grid lines indicating FDG avid peritoneal implant missed on CT (see A).

imaging is falling, in part because images are acquired faster reducing motion artifacts, and thinner slices are used, increasing sensitivity for small tumor deposits. Isolated CEA elevation with a negative conventional (CT) imaging study is now a rare scenario. A report of 272 cases of CRC that underwent FDG PET imaging found only 15 such cases, of which 14 had true-positive FDG scans, and one was false-positive. There were four patients who had symptoms, a negative work-up, and a normal CEA level, and four of whom had cases of positive FDG PET scans, of which three were false-positive

[111]. Resection of CRC metastases with or without adjuvant hepatic arterial pump therapy has led to extraordinary success with long-term follow-up demonstrating up to 60% 10-years survival [112]. Correct selection of patients for local therapy is dependent on adequate preoperative imaging, of which FDG PET plays an important role. Early studies suggested approximately 30% to 40% of patients would have their management altered on the basis of a preoperative FDG PET scan [113]. These numbers seem similar today [114]. The major role FDG plays in the staging of these patients is in the identification of extrahepatic disease, rather than staging the liver itself. In those patients receiving chemotherapy within 6 months of surgery, the authors found that FDG uptake was the strongest predictor of postoperative survival in patients who had liver resections for CRC [115].

Research continues at a rapid pace into further refining measures of metabolic activity and into the use of more tissue or disease-specific radionuclides. Investigations such as these have opened up a whole new exciting field of molecular imaging, of which PET leads the way into the future with the goal of more accurate and earlier disease detection and treatment monitoring.

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