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4'-[methyl-C-11]thiothymidine (C-11-4DST) is a novel radiopharmaceutical that can be used for tumor imaging because of its rapid incorporation into DNA as a substrate for DNA synthesis. The in vivo stability of C-11-4DST is much greater than that of natural thymidine, because of the presence of a sulfur atom in the 4'-position. Here, we evaluated the tissue kinetics and biodistribution of C-11-4DST in a rodent tumor and acute sterile inflammation model in comparison with the previously published biodistribution data of 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT), F-18-FDG, C-11-choline, C-11-methionine, and 2 sigma-receptor ligands in the same animal model. Methods: C6 tumor cells were implanted subcutaneously into the right shoulder and turpentine (0.1 mL) was injected intramuscularly into the left hind leg of male Wistar rats 11 d and 24 h, respectively, before the scanning day. The animals were anesthetized with isoflurane, and C-11-4DST (20-50 MBq) was injected intravenously. A dynamic PET scan was performed for 60 min with either the shoulder or hind leg region in the field of view. The animals were sacrificed, and a biodistribution study was performed. Results: C-11-4DST showed the highest tumor uptake (standardized uptake value, 4.93) of all radiopharmaceuticals tested. Its tumor-to-muscle concentration ratio (12.7) was similar to that of F-18-FDG (13.2). The selectivity of C-11-4DST for tumor as compared with acute inflammation was high (37.7), comparable to that of the s-ligand F-18-FE-SA5845 and much higher than that of F-18-FDG (3.5). Rapidly proliferating tissues (tumor and bone marrow) showed a steadily increasing uptake. In inflamed muscle, C-11-4DST showed relatively rapid washout, and tracer concentrations in inflamed and noninflamed muscle were not significantly different at intervals greater than 40 min. Competition of endogenous thymidine for C-11-4DST uptake in target tissues was negligible, in contrast to competition for F-18-FLT uptake. Thus, pretreatment of animals with thymidine phosphorylase was not required before PET with C-11-4DST. Conclusion: In our rodent model, 11C-4DST showed high tumor uptake (sensitivity) and high tumor selectivity. The different kinetics of C-11-4DST in rapidly proliferating and inflammatory tissue may allow distinction between tumor and acute inflammation in a clinical setting. These promising results for C-11-4DST warrant further investigation in PET studies in patients with various types of tumors.

The aims of the study were to compare the value of L-[1-C-11]tyrosine (TYR) and [F-18]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. Methods: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. Results: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG, Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). Conclusion: in this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease, SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.

The aims of the study were to compare the value of L-[1-C-11]tyrosine (TYR) and [F-18]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. Methods: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. Results: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG, Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). Conclusion: in this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease, SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.

The aims of the study were to compare the value of L-[1-C-11]tyrosine (TYR) and [F-18]fluoro-2-deoxy-D-glucose (FDG) as tumor tracers in patients with breast cancer, to investigate the correlation between quantitative values and standardized uptake values (SUVs) and to estimate the value of SUVs for the evaluation of therapy. Methods: Eleven patients with one or more malignant breast lesions and two patients with one or more benign breast tumors were studied with TYR and FDG. Doses of 300 MBq of TYR and 230 MBq of FDG were given intravenously. All PET sessions were performed using a Siemens ECAT 951/31 camera. Of 10 malignant tumors and the 3 benign lesions, glucose consumption and protein synthesis rate were quantified. All lesions were studied using SUVs based on body weight, body surface area and lean body mass, with and without correction for plasma glucose or tyrosine levels. Results: All malignant tumors were visualized with both FDG and TYR, but the visual contrast was better with FDG, Increased uptake of the tracers was seen in patients with fibrocystic tissue and complicated the visual assessment and the outlining of tumor tissue. Uptake in fibrocystic disease was more prominent with FDG than with TYR. No difference in tumor/nontumor ratio between the two tracers could be established. FDG showed a false-positive result in one benign lesion. No major differences between the SUVs as defined above were found, although the best correlation between glucose consumption and the SUV was observed when the SUV was based on body surface area and corrected for plasma glucose level (r = 0.85-0.87). The SUV based on lean body mass was found to correlate best with protein synthesis rate (r = 0.83-0.94). Conclusion: in this group of patients, TYR appears to be a better tracer than FDG for breast cancer imaging, because of lower uptake in fibrocystic disease, SUVs correlate well with quantitative values, but future studies must determine whether treatment evaluation is also reliable with SUVs.