Yanyan Zhang

Synthesis and biodistribution of a novel (⁹⁹m)TcN complex of norfloxacin dithiocarbamate as a potential agent for bacterial infection imaging.

Achieving a (⁹⁹m)Tc-labeled fluoroquinolone derivative as a single photon emission computed tomography (SPECT) tracer is considered to be of great interest. The norfloxacin dithiocarbamate (NFXDTC) was synthesized and radiolabeled with a [(⁹⁹m)TcN]²(+) intermediate to form the (⁹⁹m)TcN-NFXDTC complex in high yield. The radiochemical purity of (⁹⁹m)TcN-NFXDTC was over 90%, as measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), without any notable decomposition at room temperature over a period of 6 h. The partition coefficient and electrophoresis results indicated that (⁹⁹m)TcN-NFXDTC was lipophilic and neutral. The bacterial binding assay studies showed tht (⁹⁹m)TcN-NFXDTC had a good binding affinity. Biodistribution results in bacterial infected mice showed that (⁹⁹m)TcN-NFXDTC had a higher uptake at the sites of infection and better abscess/blood and abscess/muscle ratios than those of (⁹⁹m)Tc-ciprofloxacin and (⁹⁹m)TcN-CPFXDTC (CPFXDTC = ciprofloxacin dithiocarbamate). The biodistribution results of (⁹⁹m)TcN-NFXDTC in bacterially infected mice and in mice with turpentine-induced abscesses indicated that (⁹⁹m)TcN-NFXDTC was suited to be a bacteria-specific infection imaging agent. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in infection sites, suggesting that it would be a promising candidate for bacterial infection imaging.

Synthesis and Biodistribution of a New 99mTc-oxo Complex with Deoxyglucose Dithiocarbamate for Tumor Imaging

The deoxyglucose dithiocarbamate (DGDTC) was radiolabeled with 99mTc(V)‐glucoheptonate (GH), for the potential use as radiopharmaceuticals for tumor imaging. For labeling, 99mTcO‐DGDTC was prepared by ligand‐exchange reaction with 99mTc‐GH. The radiochemical purity of the 99mTcO‐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 6u2003h. Its partition coefficient indicated that it was a hydrophilic complex. The ligand‐exchange reaction occured at neutral condition and under 100u2003°C for 15u2003min to achieve high radiochemical purity. In vitro cell studies showed there was an increase in the uptake of 99mTcO‐DGDTC as a function of incubation time and the cellular uptake of 99mTcO‐DGDTC was possibly mediated by way of a d‐glucose mechanism. The biodistribution of 99mTcO‐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 99mTc radiolabeled glucose derivatives, 99mTcO‐DGDTC showed the highest tumor uptake and good tumor/muscle ratios. The tumor/muscle ratio of 99mTcO‐DGDTC uptake was higher than that of [18F] FDG uptake. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in tumor sites, suggesting 99mTcO‐DGDTC would be a promising candidate for tumor imaging.

Synthesis and biodistribution of novel 99mTc labeled 4-nitroimidazole dithiocarbamate complexes as potential agents to target tumor hypoxia

Sodium 3-(4-nitro-1H-imidazolyl)propyl dithiocarbamate (N4IPDTC) was synthesized and radiolabelled with a [99mTcO]3+, [99mTcN]2+ or [99mTc(CO)3]+ core to produce 99mTcO-N4IPDTC, 99mTcN-N4IPDTC and 99mTc(CO)3-N4IPDTC, respectively. All of the three complexes were prepared with high radiochemical purity and had good in vitro stability over a period of 6 h. The partition coefficient results showed that 99mTcO-N4IPDTC and 99mTcN-N4IPDTC were lipophilic, while 99mTc(CO)3-N4IPDTC was hydrophilic. The tumor cell experiments and the biodistribution in mice bearing S180 tumors showed that all of the complexes exhibited good hypoxic selectivity and accumulation in the tumor. Among them, 99mTcO-N4IPDTC had the advantages of higher tumor uptake, and higher tumor/blood and tumor/muscle ratios. Planar scintigraphic imaging studies showed there was a visible accumulation in tumor sites, suggesting its potential usefulness as a tumor hypoxia imaging agent.

Preparation and biodistribution of a 99mTc tricarbonyl complex with deoxyglucose dithiocarbamate as a tumor imaging agent for SPECT

The deoxyglucose dithiocarbamate (DGDTC) was successfully labeled with the (99m)Tc(CO)3 core to provide the corresponding (99m)Tc(CO)3-DGDTC complex in good yields. The radiochemical purity of the (99m)Tc(CO)3-DGDTC complex was over 90%, as measured by high performance liquid chromatography (HPLC). The complex possessed good stability in saline at room temperature and in mouse plasma at 37 °C. Its partition coefficient result indicated that it was a hydrophilic complex. The electrophoresis results showed the complex was neutral. The biodistribution of (99m)Tc(CO)3-DGDTC in mice bearing S 180 tumor showed that the complex clearly accumulated in tumor, exhibiting high tumor/blood and tumor/muscle ratios and good tumor retention. Single photon emission computed tomography (SPECT) image studies showed there was a visible uptake in tumor sites, suggesting (99m)Tc(CO)3-DGDTC could be considered as a potential tumor imaging agent.

(18)F-FDG PET/CT imaging of malignant hepatic solitary fibrous tumor.

Solitary fibrous tumor of the liver was rarely documented. F-FDG PET/CT imaging of malignant hepatic solitary fibrous tumor in a 49-year-old male patient was reported. The multifocal hepatic lesions demonstrated avid FDG uptake. FDG PET/CT might be potentially useful in the differentiation of benign and malignant solitary fibrous tumor.

Increased liver and spleen accumulation of Tc-99m methylene diphosphonate associated with intravenous injection of MRI contrast gadolinium-diethylenetriaminepentaacetic acid.

Several conditions that can cause diffuse hepatic or splenic uptake of Tc-99m methylene diphosphonate (Tc-99m MDP) have been previously reported. Nevertheless, diffuse abnormal liver and spleen uptake of Tc-99m MDP associated with intravenous injection of magnetic resonance imaging contrast gadolinium-diethylenetriaminepentaacetic acid is not previously known. In our series, we reported diffuse increased Tc-99m MDP activity in the liver and spleen in bone scans in patients who received Tc-99m MDP injection shortly after contrast-enhanced magnetic resonance imaging.

CT opacity in the lungs was preceded by increased MDP activity on bone scintigraphy.

Elevated 99mTc-methylene diphosphonate (MDP) uptake in the left lung was demonstrated in a 41-year-old man with chronic lymphocytic leukemia. Lung infection was considered because the patient also had fever and pancytopenia. However, the thoracic CT performed the next day did not reveal abnormality which could explain the cause of left lung MDP activity. The repeated thoracic CTs weeks later demonstrated multiple ground-glass opacity in the left lung.

Kit formulation for preparation and biological evaluation of a novel 99mTc-oxo complex with metronidazole xanthate for imaging tumor hypoxia

INTRODUCTIONnAchieving an ideal (99m)Tc labeled nitroimidazole hypoxia marker is still considered to be of great interest. Metronidazole xanthate (MNXT) ligand was synthesized and radiolabeled with (99m)Tc-glucoheptonate (GH) to form the (99m)TcO-MNXT complex, for the potential use as a novel probe for imaging tumor hypoxia.nnnMETHODSnFor labeling, (99m)TcO-MNXT was prepared by ligand-exchange reaction with (99m)Tc-GH. The radiochemical purity of the (99m)TcO-MNXT complex was measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The distribution coefficient and stability of the complex was investigated. The structure of the (99m)TcO-MNXT complex was verified by preparation and characterization of the corresponding stable rhenium complex. The cellular uptake of the (99m)TcO-MNXT complex was determined in murine sarcoma S180 cell lines under hypoxic and aerobic conditions. The biodistribution and single photon emission computed tomography (SPECT) image studies of the (99m)TcO-MNXT complex were performed in mice bearing S 180 tumor.nnnRESULTSnThe radiochemical purity of the (99m)TcO-MNXT complex was over 90%. It had good in vitro stability and its distribution coefficient indicated that it was a hydrophilic complex. When (99m)Tc and Re complexes were coinjected in HPLC, both radioactivity (for (99m)Tc complex) and UV detectors (for Re complex) showed nearly identical HPLC profiles, suggesting their structures are similar. The tumor cell experiment and the biodistribution in mice bearing S 180 tumor showed that the (99m)TcO-MNXT complex had a good hypoxic selectivity and accumulated in the tumor with high uptake and good retention. Single photon emission computed tomography (SPECT) image studies showed that the tumor detection was observable.nnnCONCLUSIONSn(99m)TcO-MNXT is prepared from a kit without the need for purification and shows high tumor uptake, tumor/blood and tumor/muscle ratios, suggesting that it would be a promising candidate for imaging tumor hypoxia.

Synthesis and biodistribution of novel 99mTcN complexes of glucose dithiocarbamate as potential probes for tumor imaging

In this study, two novel glucose dithiocarbamates (3a and 3b) were successfully synthesized via a “click chemistry” route and then radiolabeled with a [99mTcN]2+ core to prepare the corresponding 99mTcN complexes in high yields. Both of them were hydrophilic and had good in vitro stability. The in vivo biodistribution studies in mice bearing S180 tumor showed that the complexes accumulated in the tumor with high uptake and good retention. Through comparison, 99mTcN-3b had the advantages of higher tumor uptake, tumor/blood and tumor/muscle ratios at 2 h post-injection. The single-photon emission computed tomography (SPECT) image studies of 99mTcN-3b showed obvious radioactive uptake in the tumor region and the tumor-to-non-target ratio was high, suggesting that it could be regarded as a promising tumor imaging agent.

Synthesis and evaluation of a novel Tc-99m nitrido radiopharmaceutical with alendronate dithiocarbamate as a potential bone-imaging agent

Currently, a popular strategy for designing novel radioprobes as bone‐imaging agents is based on the concept of bifunctional radiopharmaceuticals. Considering the dithiocarbamate ligand can act as a suitable bifunctional linking agent to attach technetium‐99m (99mTc) to corresponding target molecules, in this study, alendronate dithiocarbamate (ALNDTC) was synthesized and radiolabeled with [99mTc≡N]2+ core by ligand exchange reaction to produce 99mTcN‐ALNDTC complex, for the potential use as a novel probe for bone imaging. The radiochemical purity of the complex was over 90%. The complex was stable in vitro and could bind to hydroxyapatite. The partition coefficient result indicated it was hydrophilic, and an evaluation of biodistribution in mice indicated that the complex exhibited a higher bone uptake than did 99mTc‐labeled methylenediphosphonate (99mTc‐MDP). Further, single photon emission computed tomography imaging study indicated clear accumulation in bone, suggesting that 99mTcN‐ALNDTC would be a promising candidate for bone imaging.