**3.2 [18F]FET**

Wester et al. (1999) were the first to introduce the fluorinated tyrosine analog [18F]FET for imaging gliomas. The longer half-life of 18F (109.7 min) relative to 11C (20 min) is more practical for production and distribution to multiple PET scanning facilities. The high *in vivo* stability of [18F]FET, fast brain and tumor uptake kinetics, low accumulation in non-tumor tissue, and ease of synthesis strongly supported evaluation of [18F]FET as an amino acid tracer for imaging gliomas.

Weber et al. (2000) compared uptakes of [18F]FET and [11C]MET by gliomas in 13 patients. On the basis of the [11C]MET-PET, viable tumor tissue were delineated in all 13 patients. The same tumors showed rapid uptake of [18F]FET with high image contrast. The mean uptake (SUV) of [11C]MET was slightly higher than [18F]FET in normal grey matter ( 1.4 ± 0.2 for [11C]MET and 1.1 ± 0.2 for [18F]FET); normal white matter (0.9 ± 0.1 for [11C]MET and 0.8 ± 0.2 for [18F]FET); and tumor lesions (3.3 ± 1.0 for [11C]MET, 2.7 ± 0.8 for [18F]FET). However, contrast between tumor and normal tissue background was not significantly different between [11C]MET and [18F]FET (**Figure 3**). In comparison to [18F]FDG-PET, a recent study found [18F]FET-PET was more accurate to detect malignant brain lesions, especially lowgrade gliomas (Lau et al. 2010).

Although there is doubt on the potential of [18F]FET-PET for grading gliomas (Popperl et al. 2004), a clinical study by Pauleit et al. (2005) showed that co-registration of [18F]FET-PET and MRI could significantly improve the sensitivity and specificity of tumor detection and correlation to histological grade of tumor. In addition, a separate study showed have shown that the kinetic profile of [18F]FET uptake for high- and low-grade lesions may be useful in grading tumors (Spence et al. 2004). In their study, tumors were classified into low (grade I and II) and high grade (grade III and IV) prior to [18F]FET-PET scans. A significant difference (p<0.05) in T/N ratio was observed between high-grade (ratio = 3.2) and lowgrade tumors (ratio = 2.0) in early time points (0-10 min post-injection). No significant differences were found at later time points (30-40 min post-injection). The importance of the kinetics of [18F]FET is not limited to grading primary tumor lesions. Low-grade recurrent tumors associated with good prognosis were differentiated from high-grade recurrent tumor associated with poor prognosis on the basis of kinetics of [18F]FET uptake (Popperl et al. 2006).

A major strength of [18F]FET-PET is that it reliably distinguishes post-operative benign lesions from recurrent tumors (Popperl et al. 2004; Popperl et al. 2006). Popperal et al. (2004)

T/N ratio and mean SUV for [11C]MET to be 1.15 and 1.78, respectively, in the radiation necrosis group (12 cases); and 1.62 and 2.5, respectively, in the tumor recurrence group (9 cases). The sensitivity and specificity of [11C]MET-PET for detection of tumor recurrence were determined to be 77.8% and 100%, respectively. In a separate study, [11C]MET-PET was shown to be superior to [18F]FDG-PET in detecting recurrent brain lesions (Chung et al. 2002). A recent study by Okamoto et al. (2010) further confirmed the utility of [11C]MET-PET to detect recurring lesions. Mean T/N ratio of all recurrent tumors and necrosis were 1.98 ± 0.62 and 1.27 ± 0.28, respectively (p < 0.01) (Okamoto et al. 2010). In smaller lesions (20 – 30 mm), T/N ratio for recurrent tumor (1.72 ± 0.44) was also significantly higher than that for necrosis (1.20 ± 0.11) (p < 0.01) (Okamoto et al. 2010). Thus, [11C]MET-PET provides high diagnostic value for recurring tumor lesions, with particular value in early diagnosis of

Wester et al. (1999) were the first to introduce the fluorinated tyrosine analog [18F]FET for imaging gliomas. The longer half-life of 18F (109.7 min) relative to 11C (20 min) is more practical for production and distribution to multiple PET scanning facilities. The high *in vivo* stability of [18F]FET, fast brain and tumor uptake kinetics, low accumulation in non-tumor tissue, and ease of synthesis strongly supported evaluation of [18F]FET as an amino acid

Weber et al. (2000) compared uptakes of [18F]FET and [11C]MET by gliomas in 13 patients. On the basis of the [11C]MET-PET, viable tumor tissue were delineated in all 13 patients. The same tumors showed rapid uptake of [18F]FET with high image contrast. The mean uptake (SUV) of [11C]MET was slightly higher than [18F]FET in normal grey matter ( 1.4 ± 0.2 for [11C]MET and 1.1 ± 0.2 for [18F]FET); normal white matter (0.9 ± 0.1 for [11C]MET and 0.8 ± 0.2 for [18F]FET); and tumor lesions (3.3 ± 1.0 for [11C]MET, 2.7 ± 0.8 for [18F]FET). However, contrast between tumor and normal tissue background was not significantly different between [11C]MET and [18F]FET (**Figure 3**). In comparison to [18F]FDG-PET, a recent study found [18F]FET-PET was more accurate to detect malignant brain lesions, especially low-

Although there is doubt on the potential of [18F]FET-PET for grading gliomas (Popperl et al. 2004), a clinical study by Pauleit et al. (2005) showed that co-registration of [18F]FET-PET and MRI could significantly improve the sensitivity and specificity of tumor detection and correlation to histological grade of tumor. In addition, a separate study showed have shown that the kinetic profile of [18F]FET uptake for high- and low-grade lesions may be useful in grading tumors (Spence et al. 2004). In their study, tumors were classified into low (grade I and II) and high grade (grade III and IV) prior to [18F]FET-PET scans. A significant difference (p<0.05) in T/N ratio was observed between high-grade (ratio = 3.2) and lowgrade tumors (ratio = 2.0) in early time points (0-10 min post-injection). No significant differences were found at later time points (30-40 min post-injection). The importance of the kinetics of [18F]FET is not limited to grading primary tumor lesions. Low-grade recurrent tumors associated with good prognosis were differentiated from high-grade recurrent tumor associated with poor prognosis on the basis of kinetics of [18F]FET uptake (Popperl et

A major strength of [18F]FET-PET is that it reliably distinguishes post-operative benign lesions from recurrent tumors (Popperl et al. 2004; Popperl et al. 2006). Popperal et al. (2004)

recurrence.

**3.2 [18F]FET** 

tracer for imaging gliomas.

grade gliomas (Lau et al. 2010).

al. 2006).

studied 53 patients with low grade (1 grade I, 9 grade II) or high grade gliomas (16 grade III, 27 grade IV) and clinically suspected recurrent tumors. The patients underwent [18F]FET-PET scans 4-180 months after various treatments. In the 42 patients with confirmed recurrence, there was additional distinct focal [18F]FET uptake with significantly higher values compared with those in the 11 patients without clinical signs of recurrence.

Fig. 3. Patient with residual tumor after subtotal resection of GBM (top) and a patient with radiation induced changes after radiotherapy for metastatic melanoma (bottom). T1 weighted contrast-enhanced MRI showing contrast enhancement in both residual tumor (A, top) and radiation induced injury (A, bottom). In the patient with residual GBM, [11C]MET-PET (B, top) and [18F]FET-PET (C, top) shows markedly increased tracer uptake. However, there is no increased uptake of [11C]MET (B, bottom) and [18F]FET (C, bottom) in radiation induced injury. *Image reproduced from work by Wolfgang A. Weber et al. (2000) and used with permission.* 
