ABSTRACT
The deoxyglucose dithiocarbamate (DGDTC) was radiolabeled with (99m) Tc(V)-glucoheptonate (GH), for the potential use as radiopharmaceuticals for tumor imaging. For labeling, (99m) TcO-DGDTC was prepared by ligand-exchange reaction with (99m) Tc-GH. The radiochemical purity of the (99m) TcO-DGDTC complex was over 90% by thin-layer chromatography and high-performance liquid chromatography, without any notable decomposition at room temperature over a period of 6 h. Its partition coefficient indicated that it was a hydrophilic complex. The ligand-exchange reaction occured at neutral condition and under 100 °C for 15 min to achieve high radiochemical purity. In vitro cell studies showed there was an increase in the uptake of (99m) TcO-DGDTC as a function of incubation time and the cellular uptake of (99m) TcO-DGDTC was possibly mediated by way of a d-glucose mechanism. The biodistribution of (99m) TcO-DGDTC in mice bearing S 180 tumor showed that the complex accumulated in the tumor with good uptake and excellent retention. As compared with other reported (99m) Tc radiolabeled glucose derivatives, (99m) TcO-DGDTC showed the highest tumor uptake and good tumor/muscle ratios. The tumor/muscle ratio of (99m) TcO-DGDTC uptake was higher than that of [(18) F] FDG uptake. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in tumor sites, suggesting (99m) TcO-DGDTC would be a promising candidate for tumor imaging.
Subject(s)
Carbamates/chemistry , Coordination Complexes/chemical synthesis , Deoxyglucose/analogs & derivatives , Neoplasms/diagnostic imaging , Radiopharmaceuticals/chemical synthesis , Animals , Cell Line, Tumor , Coordination Complexes/chemistry , Coordination Complexes/pharmacokinetics , Deoxyglucose/chemistry , Fluorodeoxyglucose F18/chemistry , Fluorodeoxyglucose F18/pharmacokinetics , Mice , Mice, Nude , Organotechnetium Compounds/chemistry , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution , Tomography, Emission-Computed, Single-PhotonABSTRACT
In the present study, the N-benzyl dithiocarbamate (BZDTC) was synthesized and radiolabeled with [(99m)TcN](2+) intermediate to form the bis(N-benzyl dithiocarbamato) nitrido technetium-99m complex [(99m)TcN(BZDTC)(2)]. The radiochemical purity of the complex was over 90% by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). It was stable over 6h at room temperature. The partition coefficient and electrophoresis results indicated that this complex was lipophilic and neutral. Biodistribution in mice showed that the complex accumulated in the brain with high uptake. The brain uptake (ID%/g) was 1.87, 1.21 and 0.85 and the brain/blood ratio was 0.75, 1.55 and 1.12 at 5, 30 and 60min post-injection, respectively. These results suggest that this complex could be a potential brain perfusion imaging agent.
Subject(s)
Brain/metabolism , Organotechnetium Compounds/chemical synthesis , Radiopharmaceuticals/chemical synthesis , Animals , Isotope Labeling , Mice , Organotechnetium Compounds/pharmacokinetics , Radiopharmaceuticals/pharmacokinetics , Tissue DistributionABSTRACT
The deoxyglucose dithiocarbamate (DGDTC) was synthesized and radiolabelled with [(99m)TcN](2+) intermediate to form the (99m)TcN-DGDTC complex. The radiochemical purity of the (99m)TcN-DGDTC complex was over 90%, as measured by TLC and by HPLC, without any notable decomposition at room temperature over a period of 6h. The partition coefficient and electrophoresis results indicated that this complex was hydrophilic and neutral. The biodistribution of (99m)TcN-DGDTC in mice bearing S 180 tumor showed that the complex accumulated in the tumor with high uptake and good retention. The tumor/blood and tumor/muscle ratios increased with time and reached 2.32 and 1.68 at 4h post-injection, suggesting it would be a promising candidate for tumor imaging.
