S180 Tumor-bearing Mice Research Articles

Preparation and biological evaluation of a technetium-99m labeled 4-nitroimidazole derivative for imaging tumor hypoxia

A novel ethylene diamine tetraacetic acid derivative of 4-nitroimidazole (EDTA-4-EtNHNM) was successfully synthesized as a carrier molecule and it was radiolabeled with 99mTc in high yield to obtain 99mTc-EDTA-4-EtNHNM, which was hydrophilic and had good in vitro stability. The tumor cell experiment and the biodistribution study in mice bearing S180 tumor showed that this complex exhibited a hypoxic selectivity and had high accumulation in tumor tissue with major clearance through urinary tract. High tumor uptake and tumor/muscle ratio of the complex suggests promise towards further evaluation.

Acupuncture Regulates the Notch Signaling Pathway in Bone Marrow Cells to Alleviate Cyclophosphamide-Induced Myelosuppression in S180 Tumor Bearing Mice

Objective: To evaluate the protein expression and distribution of Notch signaling-related, differentially expressed genes (DEGs) in the bone marrow cells of S180 tumor bearing mice. Additionally, verification of acupuncture regulated protein expression of these DEGs to protect bone marrow stem cells and alleviate cyclophosphamide (CTX) chemotherapy-induced myelosuppression was examined as well. Methods: Healthy male Kunming mice were inoculated with S180 sarcomas and further divided into blank control (group A), CTX group (group B), acupuncture (group C), and moxibustion (group D) groups. Animals in groups B, C, and D were intraperitoneally injected with single dose of 150 mg/kg CTX to generate the myelosuppressive model; while animals in group A were injected with an equivalent volume of sterile saline. After immobilizing the animals, mice in groups C and D received daily acupuncture and moxibustion, respectively at Dazhui, Geshu, Shenshu, and Zusanli acupoints; while mice in groups A and B received no daily treatment. Animals in each group were euthanized by cervical dislocation following five days of treatment and their femurs collected for marrow harvest. Small-throughput cDNA microarray was used for initial DEG screening, followed by immunohistochemistry, real-time quantitative PCR (RT-qPCR), and Western Blot analysis to detect protein expression and quantity of the Notch signaling-related DEGs in the bone marrow cells. Results: Expression of numb proteins (i.e., numb1 and numb2) was found to be up regulated while notch2 and jag1 were down regulated in bone marrow cells of acupuncture treated, tumor bearing mice. Conclusion: Acupuncture regulated the changes of Notch signaling-related DEGs in mouse bone marrow cells. The data indicates that acupuncture treatment may alleviate the CTX chemotherapy-induced myelosuppression associated with tumor burden, suggesting that might be the key mechanism to improve bone marrow function.

Synthesis and evaluation of novel F-18-labeled pyrimidine derivatives: potential FAK inhibitors and PET imaging agents for cancer detection

Compound [18F]-8a exhibited good in vivo biodistribution data in mice bearing S180 tumor. And the microPET imaging study of [18F]-8a in S180 tumor-bearing mice was also preformed, which illustrated that the uptake in S180 tumor at 60 min post-injection of [18F]-8a was obvious.

Protective Effects of Poll Gland Secretion on Immunosuppressed and S180 Tumour-Bearing Mice

The poll gland secretions (PGS) have been used traditionally for the treatment and prevention of many diseases for centuries in Inner Mongolia (China) and Mongolia. The present study was performed to evaluate the immunostimulatory activities and anti-tumour effects of PGS in vivo and in vitro. The concentration of TNF-α, IL-2, IL-6, IgG and IgM in the serum of experimental animals were measured by an enzyme-linked immunosorbent assay (ELISA) following the manufacturer's protocols and the spleen index and thymus index were calculated using the gravimetric method. The phagocytic activity of the macrophage monocytes was evaluated by a carbon clearance assay and the effect of PGS on the growth of S180 cells in vitro was examined by the determination of the IC50 of PGS. A moderate to high dose of PGS can elevate the spleen and thymus indices and significantly increase the serum concentrations of IL-6, IgG and TNF-α. Moreover, PGS can also enhance the phagocytic activities of macrophage monocytes in immunosuppressed experimental mice. On the other hand, PGS can significantly increase the concentration of serum TNF-α, IL-2 and IL-6 and directly inhibit the growth of solid tumours in mice. Additionally, PGS can also significantly inhibit the growth of S180 cells in vitro, with an IC50 of 15.63 μg/ml−1 ± 2.18.PGS can significantly improve the inhibited immune function of mice induced by cyclophosphamide (CTX) and can reduce the growth of solid tumours in vivo. In addition, PGS can also directly inhibit the S180 cell's growth in vitro, as well as considerably enhance the immune function of tumour-bearing mice.

Surface density of polyarginine influence the size, zeta potential, cellular uptake and tissue distribution of the nanostructured lipid carrier

Poly-arginines are strong tools to elevate the cellular uptake of nanopreparations. To learn the influence of poly-arginine (RRRRRRRR, R8) density on a series of properties of nanostructured lipid carrier (NLC), we build six R8 modified NLCs with different R8 densities (nR-NLC, where n represents the R8 ratio) by fusion–emulsion method with the aid of stearyl-R8. The pharmaceutical characteristics like size, zeta potential and in vitro drug release, cellular uptake, cytotoxicity to A549 cells and tissue distribution in S180 tumor-bearing mice of the six nR-NLCs are all investigated. It turns out that with as little as 2% weight ratio of stearyl-R8 modified on NLC, its pharmaceutical properties, especially zeta potential changes astonishingly; however, the stearyl-R8 ratio should be higher than 4% to upgrade the cellular uptake and cytotoxicity evidently; in the ex vivo tissue distribution assessment, the nR-NLC with less than 8% R8 showed similar tissue accumulation, while NLC with 10% R8 shows obvious acute toxicity to mice. Our study pays attention to the effect of the R8 ratio on the changes of cargo properties, and the results indicate that this topic is essential and worth to be further developed.

Folic acid-modified and functionalized CuS nanocrystal-based nanoparticles for combined tumor chemo- and photothermal therapy

Recent studies have identified that CuS nanocrystal (CuS NCs) could be used as a new class of promising photo-thermal agents due to their excellent plasmonic absorption abilities in a wide near-infrared (NIR) region. However, most of nanocarriers lack target capacity for combining chemotherapy and photothermal therapy effects. Herein, we reported chitosan (CS)-encapsulated and folic acid (FA)-modified nanoparticles (NPs) simultaneously loading with functionalized CuS NCs and docetaxel (DTX) (FA-DTX-PVP/CuS-NPs). Compared with free DTX, the photothermal agent CuS NCs and DTX not only could be specially targeted to deliver into MCF-7 cancer cells via a receptor-mediated endocytosis pathway, but also could be effectively transferred into tumor tissues of S180 tumor-bearing mice in vivo. More important, when combination with NIR laser irradiation, FA-DTX-PVP/CuS-NPs showed a higher antitumor efficacy than the individual therapies. Thus, as a remote and noninvasive tumor therapy strategy, these active targeting NPs may provide a great potential for tumor synergistic therapy.

Anti-tumor effects of (1 → 3)-β-d-glucan from Saccharomyces cerevisiae in S180 tumor-bearing mice

(1→3)-β-d-Glucan from Saccharomyces cerevisiae is a typical polysaccharide with various biological effects and is considered a candidate for the prevention and treatment of cancer in vitro. Research into the function of (1→3)-β-d-glucan in tumor-bearing animals in vivo, however, is limited. Here, we investigated the effects of (1→3)-β-d-glucan from S. cerevisiae on S180 tumor-bearing mice and on the immunity of the tumor-bearing host. The molecular mechanisms underlying the observed effects were investigated. (1→3)-β-d-Glucan was shown to exert anti-tumor effects without toxicity in normal mouse cells. The volume and weight of S180 tumors decreased dramatically following treatment with (1→3)-β-d-glucan, and treatment with the polysaccharide was furthermore shown to increase the tumor inhibition rate in a dose-dependent manner. Spleen index, T lymphocyte subsets (CD4 and CD8), as well as interleukins (IL)-2, (IL-2, IL-6), and tumor necrosis factor-α were assayed to detect the immunoregulatory and anti-tumor effects after (1→3)-β-d-glucan intragastrical administration. (1→3)-β-d-Glucan was shown to significantly potentiate the mouse immune responses by, among other effects, decreasing the ratio of CD4 to CD8. The expression levels of IL-2, IL-6, and TNF-α were also significantly increased by (1→3)-β-d-glucan. These results suggest that (1→3)-β-d-glucan enhances the host’s immune function during the tumor inhibition process. S180 tumor cells treated with (1→3)-β-d-glucan also exhibited significant apoptotic characteristics. (1→3)-β-d-glucan increased the ratio of Bax to Bcl-2 at the translation level by up-regulating Bax expression and down-regulating Bcl-2 expression, resulting in the initiation of cell apoptosis in S180 tumor-bearing mice. Taken together, these results indicate that the anti-tumor effects exerted by (1→3)-β-d-glucan may be attributed to the polysaccharide’s immunostimulating properties and apoptosis-inducing features. Further investigation into these properties and their associated mechanisms will contribute to the development of potent polysaccharide-based anti-tumor agents.

Cit/CuS@Fe3O4-based and enzyme-responsive magnetic nanoparticles for tumor chemotherapy, photothermal, and photodynamic therapy.

Safe and efficient drug delivery in a controllable fashion, especially remote and repeatable switch of on-demand drug release, is the subject of widespread attention. A kind of magnetic nanoparticles (DOX-Cit/CuS@Fe3O4-NPs) simultaneously consisted of Cit/CuS@Fe3O4 and doxorubicin (DOX) was presented. The drug release from DOX-Cit/CuS@Fe3O4-NPs could be successfully triggered by the presence of gelatinase, showing great promise for tumor-targeted drug release through an enzymatic degradation mechanism. Compared with free DOX, DOX-Cit/CuS@Fe3O4-NPs could not only specially deliver Cit/CuS@Fe3O4 and DOX into MCF-7 cells, but also could greatly improve the quantity of ROS produced in MCF-7 cells under of 980 nm laser irradiation. DOX-Cit/CuS@Fe3O4-NPs also had highly selective accumulation at tumor tissue of S180 tumor-bearing mice, which were along with a magnet near the tumor site. Furthermore, when combined with NIR laser irridation, DOX-Cit/CuS@Fe3O4-NPs showed a higher antitumor efficacy than the individual therapies invitro and invivo. This study showed that DOX-Cit/CuS@Fe3O4-NPs could be used as a platform for tumor chemotherapy, photothermal and photodynamic therapy.

Synergistic antitumor efficacy of antibacterial helvolic acid from Cordyceps taii and cyclophosphamide in a tumor mouse model.

The antibacterial agent helvolic acid, which was isolated from the active antitumor fraction of Cordyceps taii, showed potent cytotoxicity against different human cancer cells. In the present study, the invivo antitumor effect of helvolic acid was investigated in murine sarcoma S180 tumor-bearing mice. Doses of 10 and 20 mg/kg/day helvolic acid did not exert significant antitumor activity. Interestingly, co-administration of 10 mg/kg/day helvolic acid and 20 mg/kg/day cyclophosphamide (CTX) - a well-known chemotherapy drug - showed promising antitumor activity with a growth inhibitory rate of 70.90%, which was much higher than that of CTX alone (19.5%). Furthermore, the combination markedly prolonged the survival of tumor-bearing mice. In addition, helvolic acid enhanced the immune organ index. The protein expression levels of β-catenin, cyclin D1, and proliferating cell nuclear antigen were significantly suppressed in mice treated with 20 mg/kg/day helvolic acid and in those receiving combination therapy. Taken together, these results indicated that helvolic acid in combination with CTX showed potent invivo synergistic antitumor efficacy, and its mechanism of action may involve the Wnt/ β-catenin signaling pathway.

Synthesis and Biological Evaluation of Novel (99m)Tc(CO)₃-Labeled Thymidine Analogs as Potential Probes for Tumor Proliferation Imaging.

Achieving a 99mTc labeled thymidine radiotracer for single photon emission tomography (SPECT) is considered to be of interest. In this study, four novel thymidine analogs, 6a, 6b, 6c and 6d, were successfully synthesized via “click reaction” route and then radiolabeled using a [99mTc(CO)3]+ core to prepare the corresponding 99mTc(CO)3 complexes in high yields. These complexes were hydrophilic and had good in vitro stability. Biodistribution of these complexes in mice bearing S180 tumors showed that all of them exhibited accumulation in the tumors, suggesting that they would be potential tumor imaging agents.

The preventive effect and enhance immunity function of Bu-zhong-yi-qi wan on s180 tumor mice

Background: To evaluate the preventive effect and enhance immunity functions of Bu-zhong-yi-qi wan in vivo . Materials and Methods: S180 tumor mice model was established by subcutaneous injection a dose of 0.2 ml (1×10 7 /ml) at the right oxter. The inhibitory rates, spleen indexes and thymus indexes were calculated. Splenic lymphocyte proliferative activity assay and phagocytosis activity of peritoneal macrophages were done. Interferon (IFN-γ), interleukin (IL-2) and tumor necrotic factor (TNF-α) in serum were detected. Results: In the S180 tumor-bearing mice, Bu-zhong-yi-qi wan with medium-dose (975 mg/kg, 100 mg/l) had potent preventive effect and anti-tumor effect, macrophage phagocytosis and Con A-stimulated splenocyte proliferation were increased as compared with model control treatment. Bu-zhong-yi-qi wan could take part in the immune response by promoting the proliferation and differentiation of Tcells, increasing the activity of the macrophages, inducing the generation of cell factor IL-2, TNF-α, IFN-γ. Conclusion: It proved that Bu-zhong-yi-qi wan of medium-dose had great preventive effect and could enhance immunity function. Keywords: Bu-zhong-yi-qi wan, S180 tumor-bearing mice, preventive, immunity

THE PREVENTIVE EFFECT AND ENHANCE IMMUNITY FUNCTION OF BU-ZHONG-YI-QIWAN ON S180 TUMOR MICE.

Background: To evaluate the preventive effect and enhance immunity functions of Bu-zhong-yi-qi wan in vivo.
 Materials and Methods: S180 tumor mice model was established by subcutaneous injection a dose of 0.2 ml (1×107/ml) at the right
 oxter. The inhibitory rates, spleen indexes and thymus indexes were calculated. Splenic lymphocyte proliferative activity assay and
 phagocytosis activity of peritoneal macrophages were done. Interferon (IFN-γ), interleukin (IL-2) and tumor necrotic factor (TNF-α) in
 serum were detected.
 Results: In the S180 tumor-bearing mice, Bu-zhong-yi-qi wan with medium-dose (975 mg/kg, 100 mg/l) had potent preventive effect and
 anti-tumor effect, macrophage phagocytosis and Con A-stimulated splenocyte proliferation were increased as compared with model
 control treatment. Bu-zhong-yi-qi wan could take part in the immune response by promoting the proliferation and differentiation of Tcells,
 increasing the activity of the macrophages, inducing the generation of cell factor IL-2, TNF-α, IFN-γ.
 Conclusion: It proved that Bu-zhong-yi-qi wan of medium-dose had great preventive effect and could enhance immunity function.

Anti-tumor activity of exopolysaccharide from Rhizopus nigricans Ehrenb on S180 tumor-bearing mice

In this study, the effect of antitumor and immune activities of extracellular polysaccharides (EPS) from Rhizopus nigricans Ehrenb were investigated using S180 bearing mice. The results revealed that EPS in the concentration range 50–1000μg/mL can inhibited S180 cell proliferation in a dose dependent manner. EPS at the highest dose of 1000μg/mL showed significantly antitumor activity against S180 with inhibition rate of 47.53%. However, EPS significantly simulated spleen lymphocytes in the concentration of 500μg/mL, and the increase proliferation ability showed a dose-dependent effect with EPS at the dose of 50–500μg/mL. In comparison with the control groups, the weights of tumor were declined and the inhibition rates of tumor were remarkably decreased in the treated groups. Pretreatment with EPS at the dose of 75mg/kg/day, the inhibition rate was decreased by 44.38% (P<0.05). EPS increased the concentrations of IL-2 and TNF-a. The pathological changes of model control group were very obvious. Meanwhile, the prophylactic administration of EPS could more efficiently inhibit the growth of S180 tumor than direct administration of EPS. EPS could prolong the survival period of S180 tumor bearing mice, and the doses 75mg/kg/day of EPS and combined with cyclophosphamide (20mg/kg/day) were 43.36% and 36.28% respectively compared to control groups (P<0.05). The results suggested EPS confirmed in vivo anti-tumor effects observed in vitro, and the mechanism of anti-tumor effect of EPS may be at least in part mediated by increased immune activity in host.

Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo

It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 μM. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future.

Antitumor activity of Dendrobium devonianum polysaccharides based on their immunomodulatory effects in S180 tumor-bearing mice

The aim of the present study is to investigate the antitumor activity and immunostimulatory effect of the water-soluble polysaccharides (DDP) from stem of Dendrobium devonianum in S180 tumor-bearing mice.

Production of immunoregulatory polysaccharides from Crassostrea hongkongensis and their positive effects as a nutrition factor in modulating the effectiveness and toxicity of 5-FU chemotherapy in mice.

Chemotherapy is generally accompanied by undesirable side effects, such as immunosuppression and malnutrition, which reduce tolerance to cancer therapies. Prior studies have shown that immunonutrition improves the clinical outcomes of cancer patients. In this study, immunoregulatory polysaccharides from Crassostrea hongkongensis were included in a nutrition formula that was administered to S180 tumor-bearing mice in combination with 5-fluorouracil (5-FU) treatment. The C30-60% fraction of the polysaccharides was characterized as a branched polysaccharide, with a high amount of d-glucose (96.76% of the total) and the highest uronic acid and sulfate groups' content among all of the polysaccharide fractions. The C30-60% polysaccharide fraction showed a maximal proliferative effect on RAW264.7 cells and T lymphocytes at a concentration of 0.0391 mg mL(-1) and 0.0781 mg mL(-1), respectively. Moreover, the combination treatment of the C30-60% polysaccharide-based nutrition formula (OPNF) with the administration of 5-FU effectively inhibited the growth of tumors and notably increased the leucocyte and lymphocyte counts in S180 tumor-bearing mice. In addition, a slight increase in the erythrocyte and hemoglobin values was observed in the mice treated with the combination of OPNF and 5-FU. These results suggest that supplementation with a C30-60%-based enteral formula would be beneficial for patients undergoing chemotherapy with 5-FU.

In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting.

The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain-promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components: an azide group linked to 2-nitroimidazole (2NIM-Az) serves for tumor hypoxia-targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole-MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98M(-1)s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; (99m)Tc-AM and (99m)Tc-triazole-2NIM were used as blank control and conventional control. Compared to the control groups, the pretargeting experiment exhibits the best radio-uptake and retention in tumor, with higher tumor-to-muscle and tumor-to-blood ratios (up to 8.55 and 1.44 at 8h post-(99m)Tc-complex-injection, respectively). To some extent, the pretargeting strategy protects the bioactivity of nitroimidazole and therefore provides an innovative approach for the development of tumor hypoxia-SPECT imaging agents.

Investigation on Single-walled Carbon Nanotubes-Liposomes Conjugate to Treatment Tumor with Dual-mechanism.

Single-walled carbon nanotubes (SWNT) have been widely explored as carriers for drug delivery because of their large surface area, high near-infrared absorption coefficient and facile transport through cellular membranes. In this study, Lysine (Lys) modified SWNT-liposomes conjugate loaded with doxorubicin (DOX) was designed to enhance the targeted drug delivery and antitumor effect. The conjugate (DOX-Lys/SWNT-Lip) was prepared with pH gradient methods, and the mean particle size and drug entrapment efficiency were 223±5.9 nm and 85.9 %, respectively. In vitro drug release study showed that DOX released much slowly from DOX-Lys/SWNT-Lip than from DOX solution, but faster than that of DOX-Lys/SWNT. DOX-Lys/SWNT-Lip could efficiently cross the cell membrane and afford higher anti-tumor efficacy on MCF-7 cells in vitro. For in vivo experiment, normal saline (N.S.), and DOX or DOX-Lys/SWNTLip were given to the S180 tumor bearing mice by i.v. administration, and followed by exposing the tumor site to nearinfrared laser (NIR) irradiation at 808 nm for 2 min. The relative tumor volumes in DOX-Lys/SWNT-Lip group and DOX group were obviously smaller than those of N.S. group. When combined with NIR laser irradiation, the suppression on tumor growth was much stronger. In conclusion, this study may provide potentially viable clinical strategies for tumor treatment with chemotherapy and photothermal therapy dual-mechanism.

Characterization of 9-nitrocamptothecin-in-cyclodextrin-in-liposomes modified with transferrin for the treating of tumor

Encapsulation of hydrophobic drugs in the form of drug-cyclodextrin (CD) complex in liposomes has been applied as a novel strategy to combine the relative advantages of CDs and liposomes into one system, naming drug-in-CD-in-liposome (DCL). In the present study, soluble 9-NC/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes were prepared using the freeze-drying technique. Then 9-NC inclusion complexes were further encapsulated into liposomes by ethanol injection method and transferrin (Tf) was conjugated to the surface of 9-NC DCL to obtain Tf modified 9-NC DCL (Tf-9-NC-CL). Compared to PEGylated 9-NC DCL (P-9-NC-CL), the lactone stability and vesicle stability of Tf-9-NC-CL were significantly increased. Both 9-NC and HP-β-CD were found to release from the DCL and Tf modification resulted in reduced release of them. The enhanced targeting efficiency of the Tf-modified liposomes was demonstrated by flow cytometry and confocal microscopy. In vivo pharmacokinetics in rats showed improved lactone stability of 9-NC following intravenous injection of Tf-9-NC-CL. The cytotoxicity of Tf-9-NC-CL against tumor cells and normal cells was investigated in vitro and the antitumor efficacy was evaluated in S180 tumor-bearing mice in vivo. Compared with free 9-NC, 9-NC inclusion complexes and P-9-NC-CL, Tf-9-NC-CL demonstrated the strongest cytotoxicity to tumor cells. And the inhibitory rate of tumor (IRT) values were determined to be 43.08%, 56.92%, 67.69% and 80.00% for 9-NC solution, inclusion complexes, P-9-NC-CL and Tf-9-NC-CL, respectively. In conclusion, Tf modification can be useful in increasing vesicle stability, targeting drug delivery efficiency and antitumor efficacy of DCL containing hydrophobic antitumor drugs, such as 9-NC.

Synthesis and biological evaluation of novel 99mTc labeled ornidazole xanthate complexes as potential hypoxia imaging agents

In this study, ornidazole xanthate (ONXT) ligand was successfully synthesized and its 99mTc-nitrido core, 99mTc-oxo core and [99mTc(CO)3]+ core complexes were prepared with high yields. The tumor cell experiments and the biodistribution in mice bearing S180 tumor showed that all of the complexes had a certain hypoxic selectivity and tumor uptake. Among them, 99mTcO-ONXT exhibited the highest tumor uptake and tumor/muscle ratio. Planar scintigraphic imaging studies showed the tumor detection was observable, suggesting it would be a potential radiotracer to target tumor hypoxia.