o-(2-fluoroethyl)tyrosine and Neoplasms

O-(2-18F-Fluoroethyl)-L-Tyrosine (18F-FET) PET has shown promising results in brain tumor diagnosis. The aim of this prospective study was to evaluate 18F-FET PET in comparison with 18F-FDG PET in patients with peripheral tumors.. Forty-four consecutive patients with suspected malignant tumors underwent 18F-FET PET and 18F-FDG PET within 7 d. Whole-body PET studies were performed 1 h after intravenous injection of 370 MBq of 18F-FET or 18F-FDG. Six patients were excluded from the analysis because a malignant tumor could not be verified. In 38 patients (7 with colorectal cancer, 6 with pancreatic cancer, 9 with head-neck cancer, 4 with lymphomas, 3 with lung cancer, 3 with ovarian cancer, 4 with breast cancer, and 2 with prostatic cancer), 18F-FET PET and 18F-FDG PET were compared.. 18F-FET was positive in only 13 of 38 patients (8 with head-neck cancer, 3 with breast cancer, and 2 with lung cancer), whereas 18F-FDG exhibited increased uptake in 37 of 38 patients. All squamous cell carcinomas were found to be 18F-FET-positive tumors (8 head-neck cancer and 2 lung cancer), whereas most adenocarcinomas were found to be 18F-FET-negative tumors. In patients with colorectal cancer, pancreatic cancer, ovarian cancer, prostatic cancer, and lymphomas, no increased 18F-FET uptake could be identified. All lesions that exhibited increased 18F-FET uptake also showed increased 18F-FDG uptake. No additional lesion was identified by 18F-FET PET but not by 18F-FDG PET. A subgroup analysis of patients with head-neck carcinomas allowed a better distinction between malignant and inflammatory tissues with 18F-FET than with 18F-FDG.. 18F-FET is inferior to 18F-FDG as a PET tracer for general tumor diagnosis. Our preliminary results suggest rather selective uptake of 18F-FET in squamous cell carcinomas. Compared with 18F-FDG PET, 18F-FET PET may allow a better distinction between tumors and inflammatory tissues in patients with squamous cell carcinomas.

Topics: Adult; Aged; Feasibility Studies; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Neoplasms; Pilot Projects; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tyrosine

The goal of this study was to compare the glucose analog, 2-[18F]fluoro-2-deoxy-d-glucose ([18F]-FDG), the amino acid analog, o-(2-[18F]fluoroethyl)-l-tyrosine ([18F]-FET) and nucleoside analog, 3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) with regard to their feasibility for differentiating tumors from inflammation.. In Fisher rat models bearing both 9L tumor and inflammation, the biodistributions and positron emission tomography (PET) images of [18F]-FDG, [18F]-FET and [18F]-FLT at 60 min post injection were compared. Pretreatment with thymidine phosphorylase before injection of [18F]-FLT was performed.. The tumor-to-blood (T/B) and tumor-to-muscle (T/M) ratios of [18F]-FDG were significantly higher than those of [18F]-FET and [18F]-FLT (P<.01); however, the accumulation of [18F]-FDG [1.23+/-0.52 percent injected dose per gram of tissue (%ID/g)] in inflammation was also elevated. T/B and T/M ratios of [18F]-FET (2.3+/-0.5 and 2.2+/-0.5) were higher than those of [18F]-FLT (1.6+/-0.6 and 1.6+/-0.5), and inflammation uptake of those tracers was very low (0.63+/-0.19 and 0.27+/-0.16 %ID/g, respectively). [18F]-FET and [18F]-FLT showed higher selectivity indices (tumor-to-inflammation ratio corrected background) than [18F]-FDG. In PET images, [18F]-FDG was found to be accumulated in both tumor and inflammation, but [18F]-FET and [18F]-FLT selectively localized in tumor.. Our data confirm the result of previous studies that [18F]-FET and [18F]-FLT are superior to [18F]-FDG in differentiating tumor from inflammation.

Topics: Animals; Diagnosis, Differential; Dideoxynucleosides; Feasibility Studies; Female; Fluorodeoxyglucose F18; Inflammation; Neoplasms; Positron-Emission Tomography; Rats; Thymidine Phosphorylase; Tissue Distribution; Tyrosine

O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) is one of the first (18)F-labeled amino acids for imaging amino acid metabolism in tumors. This tracer overcomes the disadvantages of [(18)F]fluorodeoxyglucose, [(18)F]FDG, and [(11)C]methionine, [(11)C]MET. Nevertheless, the various synthetic methods providing (18)F[FET] exhibit a big disadvantage concerning the necessity of two purification steps during the synthesis including HPLC purification, which causes difficulties in the automation, moderate yields, and long synthesis times >60 min. A new approach for the synthesis of [(18)F]FET is developed starting from 2-bromoethyl triflate as precursor. After optimization of the synthesis parameters including the distillation step of [(18)F]-FCH(2)CH(2)Br combined with the final purification of [(18)F]FET using a simple solid phase extraction instead of an HPLC run the synthesis [(18)F]FET could be significantly simplified, shortened, and improved. The radiochemical yield (RCY) was about 45% (not decay corrected and calculated relative to [(18)F]F(-) activity that was delivered from the cyclotron). Synthesis time was only 35 min from the end of bombardment (EOB) and the radiochemical purity was >99% at the end of synthesis (EOS). Thus, this simplified synthesis for [(18)F]FET offers a very good option for routine clinical use.

Topics: Automation; Chromatography, Gas; Neoplasms; Radiopharmaceuticals; Solid Phase Extraction; Spectrometry, Mass, Electrospray Ionization; Tyrosine

The ability to monitor tumor responses during prodrug activation gene therapy and other anticancer gene therapies is critical for their translation into clinical practice. Previously, we demonstrated the feasibility of noninvasive in vivo imaging with 131I-5-iodo-2'-fluoro-1-beta-D-arabinofuranosyluracil (131I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer gene expression in an experimental animal model. Here we tested the efficacy of SPECT with 123I-FIAU and PET with 5-18F-fluoro-2'-deoxyuridine (18F-FUdR), 2-18F-fluoroethyl-L-tyrosine (18F-FET), and 18F-FDG for monitoring tumor responses during prodrug activation gene therapy with HSV1-tk and ganciclovir (GCV).. In the flanks of FVB/N female mice, 4 tumors per animal were established by subcutaneous injection of 1 x 10(5) cells of NG4TL4 sarcoma cells, HSV1-tk-transduced NG4TL4-STK cells, or a mixture of these cells in different proportions to model different efficacies of transfection and HSV1-tk gene expression levels in tumors. Ten days later, the animals were treated with GCV (10 mg/kg/d intraperitoneally) for 7 d. Gamma-Imaging with 123I-FIAU and PET with 18F-FUdR, 18F-FET, and 18F-FDG were performed before and after initiation of therapy with GCV in the same animal.. Before GCV treatment, no significant difference in weight and size was found in tumors that expressed different HSV1-tk levels, suggesting similar in vivo proliferation rates for NG4TL4 and NG4TL4-STK sarcomas. The accumulation of 123I-FIAU at 24 h after injection was directly proportional to the percentage of NG4TL4-STK cells in the tumors. The 123I-FIAU accumulation at 4 and 7 d of GCV therapy decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. Tumor uptake of 18F-FUdR in all HSV1-tk-expressing tumors also decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. The accumulation of 18F-FET decreased minimally (about 1.5-fold) and 18F-FDG decreased only 2-fold after 7 d of GCV therapy, and the degree of reduction was proportional to the percentage of HSV1-tk-positive tumor cells.. We have shown that gamma-camera imaging with 123I-FIAU was the most reliable method for prediction of tumor response to GCV therapy, which was proportional to the magnitude of HSV1-tk expression in tumor tissue. 123I-FIAU imaging can be used to verify the efficacy of elimination of HSV1-tk-expressing cells by therapy with GCV. PET with 18F-FUdR reliably visualizes proliferating tumor tissue and is most suitable for the assessment of responses in tumors undergoing HSV1-tk plus GCV prodrug activation gene therapy. PET with 18F-FDG or 18F-FET can be used as additional "surrogate" biomarkers of the treatment response, although these radiotracers are less sensitive than 18F-FUdR for monitoring tumor responses to prodrug activation gene therapy with HSV1-tk and GCV in this sarcoma model.

Topics: Animals; Antiviral Agents; Arabinofuranosyluracil; Cell Line, Tumor; Female; Floxuridine; Fluorodeoxyglucose F18; Ganciclovir; Genetic Therapy; Herpesvirus 1, Human; Humans; Iodine Radioisotopes; Mice; Neoplasms; Prodrugs; Thymidine Kinase; Tyrosine