O-(2-[18F]Fluoroethyl)-L-tyrosine (FET): a tracer for differentiation of tumour from inflammation in murine lymph nodes

Abstract

High uptake of [(18)F]fluoro-2-deoxy- D-glucose (FDG) by inflammatory cells is a frequent cause of false positive results in lymph node (LN) staging by positron emission tomography. Previous studies suggest that radiolabelled amino acids may be more specific markers for viable tumour tissue than FDG. The aim of this study was to investigate quantitatively the uptake of FDG, [(3)H]methyl- L-methionine (MET) and O-2-([(18)F]fluoroethyl)- L-tyrosine (FET) in tumour-infiltrated and immunologically stimulated LNs. Popliteal LNs of Balb/c and DBA/2 mice were stimulated by injection into the right posterior foot pad of mice of either streptozotocin (STZ), causing chronic lymphadenitis, or concanavalin A (Con A), resulting in acute lymphadenitis. Tumour-infiltrated popliteal LNs were induced by inoculation of 2x10(5) lacZ-tagged T cell mouse lymphoma cells into the right posterior foot pad of syngeneic mice. Twenty-one days post inoculation of tumour cells or at various time points after STZ or Con A injection, mice were simultaneously injected intravenously with MET and FDG or MET and FET. After 30 min, mice were sacrificed and tracer uptake was determined in popliteal LNs. Contralateral LNs and LNs of untreated mice served as controls. Histopathological and immunohistochemical analysis demonstrated typical signs of chronic inflammation (non-specific sinus hyperplasia with macrophages) in STZ-treated animals and acute inflammatory changes (accumulation of neutrophilic granulocytes, vascular dilation, follicular hyperplasia) in Con A-treated animals. X-Gal staining confirmed the presence of tumour cells in the LNs of the injected side of tumour-inoculated mice. In the chronic lymphadenitis model, FDG uptake increased 3.0+/-0.1 fold [from 2.7+/-0.2 to 8.2+/-1.2 percent of injected dose per gram tissue (%ID/g)] and MET uptake 2.0+/-0.01 fold (from 4.5+/-0.6 to 9.2+/-1.1 %ID/g). In the acute lymphadenitis model, FDG uptake increased 3.9+/-0.3 fold (from 2.7+/-0.2 to 10.6+/-2.4 %ID/g) and MET uptake 1.9+/-0.1 fold (from 4.5+/-0.6 to 8.5+/-1.4 %ID/g). In contrast, FET uptake in both lymphadenitis models (1.0+/-0.03 and 1.2+/-0.04 fold) was not significantly different from that in controls (from 4.2+/-0.3 to 4.7+/-0.7 and to 5.1+/-0.4 %ID/g, respectively). Uptake of all three tracers in tumour-infiltrated LNs was significantly higher than that in control LNs. FDG uptake increased 2.8+/-0.15 fold (from 2.7+/-0.2 to 7.6+/-1.3%ID/g), MET uptake 1.7+/-0.11 fold (from 4.5+/-0.6 to 7.5+/-1.3 %ID/g) and FET uptake 2.4+/-0.15 fold (from 4.2+/-0.3 to 10.0+/-1.8 %ID/g). MET and FDG uptake was similar or higher in inflammatory than in tumour-infiltrated LNs ( P=0.01 and P<0.01, respectively). In contrast, uptake of FET showed no overlap between tumour-infiltrated and inflammatory LNs ( P<0.00001). In conclusion, tumour-infiltrated and inflammatory LNs could not be differentiated by means of FDG and MET uptake. FET, in contrast, proved to be a specific tracer for differentiating between tumour-infiltrated and inflammatory LNs in the murin...

Evaluation of d-18F-FMT, 18F-FDG, l-11C-MET, and 18F-FLT for Monitoring the Response of Tumors to Radiotherapy in Mice

“…However, recent rodent and clinical studies of L-11 C-MET-PET have demonstrated a definite increase in the tissue accumulation of L-11 C-MET in various inflammatory processes (28)(29)(30). The uptake of 18 F-FDG, L-11 C-MET, and L-18 F-FET, an amino acid transport ligand, in tumorinfiltrated and immunologically stimulated lymph nodes revealed increased uptake of 18 F-FDG and L-11 C-MET in both tissues (31). In contrast, L-18 F-FET proved to be a specific PET ligand for discrimination between tumorinfiltrated and inflammatory lymph nodes in the murine models studied.…”

Comparison of the Amino Acid Tracers18F-FET and18F-DOPA in High-Grade Glioma Patients

“…18 F-DOPA demonstrated superior contrast ratios for lesions outside the striatum (23). The authors argued that 18 F-DOPA uptake occurs via both the LAT1 and the LAT2 systems, whereas 18 F-FET is mainly transported by LAT2 (29,32). However, the in vivo relevance of this phenomenon for the pharmacokinetics of 18 F-DOPA versus those of 18 F-FET remains unknown (33).…”

PET/CT of Skull Base Meningiomas Using 2-18F-Fluoro-L-Tyrosine: Initial Report

“…The clinical relevance of such a hypothesis remains unclear, however. Animal studies have shown low or no uptake of 18 F-FET in inflammatory lesions (30), but false-positive results have been reported in human lesions such as abscesses (31). Little is known about the specificity of 18 F-TYR, but there were no false positive results in a series of 23 patients with non-small cell lung cancer or lymphoma (32).…”