Evaluation of 4 '-[Methyl-C-11]Thiothymidine in a Rodent Tumor and Inflammation Model

Jun Toyohara*, Philip H. Elsinga, Kiichi Ishiwata, JurgenW. A. Sijbesma, Rudi A. J. O. Dierckx, Aren van Waarde

*Corresponding author for this work

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Abstract

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.

Original languageEnglish
Pages (from-to)488-494
Number of pages7
JournalJournal of Nuclear Medicine
Volume53
Issue number3
DOIs
Publication statusPublished - 1-Mar-2012

Keywords

  • 4DST
  • tumor
  • inflammation
  • FLUORINATED THYMIDINE DERIVATIVES
  • IMAGING CELL-PROLIFERATION
  • DIFFERENTIATING TUMOR
  • GRANULATION TISSUES
  • EMISSION-TOMOGRAPHY
  • HIGH ACCUMULATION
  • SIGMA-RECEPTORS
  • PROSTATE-CANCER
  • BRAIN-TUMORS
  • PET

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