{'fraction_non_alphanumeric': 0.042644757433489826, 'fraction_numerical': 0.037949921752738654, 'mean_word_length': 5.002347417840376, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Evaluation of 4′-[Methyl-11C]Thiothymidine in a Rodent Tumor and Inflammation Model

4′-[methyl-11C]thiothymidine (11C-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 11C-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 11C-4DST in a rodent tumor and acute sterile inflammation model in comparison with the previously published biodistribution data of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT), 18F-FDG, 11C-choline, 11C-methionine, and 2 σ-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 11C-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: 11C-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 18F-FDG (13.2). The selectivity of 11C-4DST for tumor as compared with acute inflammation was high (37.7), comparable to that of the σ-ligand 18F-FE-SA5845 and much higher than that of 18F-FDG (3.5). Rapidly proliferating tissues (tumor and bone marrow) showed a steadily increasing uptake. In inflamed muscle, 11C-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 11C-4DST uptake in target tissues was negligible, in contrast to competition for 18F-FLT uptake. Thus, pretreatment of animals with thymidine phosphorylase was not required before PET with 11C-4DST. Conclusion: In our rodent model, 11C-4DST showed high tumor uptake (sensitivity) and high tumor selectivity. The different kinetics of 11C-4DST in rapidly proliferating and inflammatory tissue may allow distinction between tumor and acute inflammation in a clinical setting. These promising results for 11C-4DST warrant further investigation in PET studies in patients with various types of tumors.