18 results on '"Barnhart, Todd E."'
Search Results
2. ImmunoPET imaging of CD38 in murine lymphoma models using 89Zr-labeled daratumumab
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Kang, Lei, Jiang, Dawei, England, Christopher G., Barnhart, Todd E., Yu, Bo, Rosenkrans, Zachary T., Wang, Rongfu, Engle, Jonathan W., Xu, Xiaojie, Huang, Peng, and Cai, Weibo
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- 2018
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3. 89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer
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England, Christopher G., Jiang, Dawei, Ehlerding, Emily B., Rekoske, Brian T., Ellison, Paul A., Hernandez, Reinier, Barnhart, Todd E., McNeel, Douglas G., Huang, Peng, and Cai, Weibo
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- 2018
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4. ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer
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Sun, Haiyan, England, Christopher G., Hernandez, Reinier, Graves, Stephen A., Majewski, Rebecca L., Kamkaew, Anyanee, Jiang, Dawei, Barnhart, Todd E., Yang, Yunan, and Cai, Weibo
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- 2016
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5. Imaging tumor angiogenesis in breast cancer experimental lung metastasis with positron emission tomography, near-infrared fluorescence, and bioluminescence
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Zhang, Yin, Hong, Hao, Nayak, Tapas R., Valdovinos, Hector F., Myklejord, Duane V., Theuer, Charles P., Barnhart, Todd E., and Cai, Weibo
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- 2013
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6. PET imaging of CD105/endoglin expression with a 61/64Cu-labeled Fab antibody fragment
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Zhang, Yin, Hong, Hao, Orbay, Hakan, Valdovinos, Hector F., Nayak, Tapas R., Theuer, Charles P., Barnhart, Todd E., and Cai, Weibo
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- 2013
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7. Positron emission tomography imaging of CD105 expression with 89Zr-Df-TRC105
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Hong, Hao, Severin, Gregory W., Yang, Yunan, Engle, Jonathan W., Zhang, Yin, Barnhart, Todd E., Liu, Glenn, Leigh, Bryan R., Nickles, Robert J., and Cai, Weibo
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- 2012
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8. Positron emission tomography imaging of CD105 expression during tumor angiogenesis
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Hong, Hao, Yang, Yunan, Zhang, Yin, Engle, Jonathan W., Barnhart, Todd E., Nickles, Robert J., Leigh, Bryan R., and Cai, Weibo
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- 2011
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9. CD38‐Targeted Theranostics of Lymphoma with 89Zr/177Lu‐Labeled Daratumumab.
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Kang, Lei, Li, Cuicui, Rosenkrans, Zachary T., Huo, Nan, Chen, Zhao, Ehlerding, Emily B., Huo, Yan, Ferreira, Carolina A., Barnhart, Todd E., Engle, Jonathan W., Wang, Rongfu, Jiang, Dawei, Xu, Xiaojie, and Cai, Weibo
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DARATUMUMAB ,B cell lymphoma ,BURKITT'S lymphoma ,POSITRON emission tomography ,LYMPHOMAS - Abstract
Lymphoma is a heterogeneous disease with varying clinical manifestations and outcomes. Many subtypes of lymphoma, such as Burkitt′s lymphoma and diffuse large B cell lymphoma, are highly aggressive with dismal prognosis even after conventional chemotherapy and radiotherapy. As such, exploring specific biomarkers for lymphoma is of high clinical significance. Herein, a potential marker, CD38, is investigated for differentiating lymphoma. A CD38‐targeting monoclonal antibody (mAb, daratumumab) is then radiolabeled with Zr‐89 and Lu‐177 for theranostic applications. As the diagnostic component, the Zr‐89‐labeled mAb is highly specific in delineating CD38‐positive lymphoma via positron emission tomography (PET) imaging, while the Lu‐177‐labeled mAb serves well as the therapeutic component to suppress tumor growth after a one‐time administration. These results strongly suggest that CD38 is a lymphoma‐specific marker and prove that 89Zr/177Lu‐labeled daratumumab facilitates immunoPET imaging and radioimmunotherapy of lymphoma in preclinical models. Further clinical evaluation and translation of this CD38‐targeted theranostics may be of significant help in lymphoma patient stratification and management. [ABSTRACT FROM AUTHOR]
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- 2021
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10. ImmunoPET imaging of CD38 in murine lymphoma models using 89Zr-labeled daratumumab.
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Kang, Lei, Jiang, Dawei, England, Christopher G., Barnhart, Todd E., Yu, Bo, Rosenkrans, Zachary T., Wang, Rongfu, Engle, Jonathan W., Xu, Xiaojie, Huang, Peng, and Cai, Weibo
- Subjects
POSITRON emission tomography ,BCL-2 proteins ,CD38 antigen ,HEMATOLOGICAL oncology ,CANCER - Abstract
Purpose: CD38 is considered a potential biomarker for multiple myeloma (MM) and has shown a strong link with chronic lymphocytic leukemia due to high and uniform expression on plasma cells. In vivo evaluation of CD38 expression may provide useful information about lesion detection and prognosis of treatment in MM. In this study, immunoPET imaging with
89 Zr-labeled daratumumab was used for differentiation of CD38 expression in murine lymphoma models to provide a potential non-invasive method for monitoring CD38 in the clinic.Methods: Daratumumab was radiolabeled with89 Zr (t1/2 = 78.4 h) via conjugation with desferrioxamine (Df). After Western blot (WB) was used to screen CD38 expression in five lymphoma cell lines, flow cytometry and cellular binding assays were performed to test the binding ability of labeled or conjugated daratumumab with CD38 in vitro. PET imaging and biodistribution studies were performed to evaluate CD38 expression after injection of89 Zr-Df-daratumumab.89 Zr-Df-IgG was also evaluated as a non-specific control group in the Ramos model. Finally, CD38 expression in tumor tissues was verified by histological analysis.Results: Using WB screening, the Ramos cell line was found to express the highest level of CD38 while the HBL-1 cell line had the lowest expression. Df-conjugated and89 Zr-labeled daratumumab displayed similar high binding affinities with Ramos cells. PET imaging of89 Zr-Df-daratumumab showed a high tumor uptake of up to 26.6 ± 8.0 %ID/g for Ramos at 120 h post-injection, and only up to 6.6 ± 2.9 %ID/g for HBL-1 (n = 4). Additionally,89 Zr-Df-IgG demonstrated a low tumor uptake in the Ramos model (only 4.3 ± 0.8 %ID/g at 120 h post-injection). Ex vivo biodistribution studies showed similar trends with imaging results. Immunofluorescence staining of tumor tissues verified higher CD38 expression of Ramos than that of HBL-1.Conclusions: The role of89 Zr-Df-daratumumab was investigated for evaluating CD38 expression in lymphoma models non-invasively and was found to be to a promising imaging agent of CD38-positive hematological diseases such as MM in future clinical applications. [ABSTRACT FROM AUTHOR]- Published
- 2018
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11. Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer.
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England, Christopher G., Dawei Jiang, Ehlerding, Emily B., Rekoske, Brian T., Ellison, Paul A., Hernandez, Reinier, Barnhart, Todd E., McNeel, Douglas. G, Peng Huang, and Weibo Cai
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LUNG cancer ,APOPTOSIS ,MONOCLONAL antibodies ,T cells ,CELLULAR control mechanisms ,TUMORS - Abstract
Purpose: Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes. Methods: Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer. The tracer was developed by radiolabeling the antibody with the positron emitter zirconium-89 (Zr). Imaging results were validated by ex vivo biodistribution studies, and PD-1 expression was validated by immunohistochemistry. Data obtained from PET imaging were used to determine human dosimetry estimations. Results: The tracer showed elevated binding to stimulated PD-1 expressing T-cells in vitro and in vivo. PET imaging of Zr-Df-nivolumab allowed for clear delineation of subcutaneous tumors through targeting of localized activated T-cells expressing PD-1 in the tumors and salivary glands of humanized A549 tumor-bearing mice. In addition to tumor uptake, salivary and lacrimal gland infiltration of T-cells was noticeably visible and confirmed via histological analysis. Conclusions: These data support our claim that PD-1-targeted agents allow for tumor imaging in vivo, which may assist in the design and development of new immunotherapies. In the future, noninvasive imaging of immunotherapy biomarkers may assist in disease diagnostics, disease monitoring, and patient stratification. [ABSTRACT FROM AUTHOR]
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- 2018
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12. Positron emission tomography imaging of CD105 expression during tumor angiogenesis.
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Hao Hong, Yang, Yunan, Zhang, Yin, Engle, Jonathan W., Barnhart, Todd E., Nickles, Robert J., Leigh, Bryan R., and Weibo Cai
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POSITRON emission tomography ,BLOOD-vessel development ,MEDICAL microscopy ,CETUXIMAB ,TRANSGENIC mice ,UMBILICAL veins ,FLUORESCENCE microscopy - Abstract
Purpose: Overexpression of CD105 (endoglin) correlates with poor prognosis in many solid tumor types. Tumor microvessel density (MVD) assessed by CD105 staining is the current gold standard for evaluating tumor angiogenesis in the clinic. The goal of this study was to develop a positron emission tomography (PET) tracer for imaging CD105 expression. Methods: TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and labeled with Cu. FACS analysis and microscopy studies were performed to compare the CD105 binding affinity of TRC105 and DOTA-TRC105. PET imaging, biodistribution, blocking, and ex vivo histology studies were performed on 4T1 murine breast tumor-bearing mice to evaluate the ability of Cu-DOTA-TRC105 to target tumor angiogenesis. Another chimeric antibody, cetuximab, was used as an isotype-matched control. Results: FACS analysis of human umbilical vein endothelial cells (HUVECs) revealed no difference in CD105 binding affinity between TRC105 and DOTA-TRC105, which was further validated by fluorescence microscopy. Cu labeling was achieved with high yield and specific activity. Serial PET imaging revealed that the 4T1 tumor uptake of the tracer was 8.0 ± 0.5, 10.4 ± 2.8, and 9.7 ± 1.8%ID/g at 4, 24, and 48 h post-injection, respectively ( n = 3), higher than most organs at late time points which provided excellent tumor contrast. Biodistribution data as measured by gamma counting were consistent with the PET findings. Blocking experiments, control studies with Cu-DOTA-cetuximab, as well as ex vivo histology all confirmed the in vivo target specificity of Cu-DOTA-TRC105. Conclusion: This is the first successful PET imaging study of CD105 expression. Fast, prominent, persistent, and CD105-specific uptake of the tracer in the 4T1 tumor was observed. Further studies are warranted and currently underway. [ABSTRACT FROM AUTHOR]
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- 2011
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13. ImmunoPET imaging of tissue factor expression in pancreatic cancer with 89Zr-Df-ALT-836.
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Hernandez, Reinier, England, Christopher G., Yang, Yunan, Valdovinos, Hector F., Liu, Bai, Wong, Hing C., Barnhart, Todd E., and Cai, Weibo
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PANCREATIC cancer diagnosis , *THROMBOPLASTIN , *POSITRON emission tomography , *PANCREATIC cancer treatment , *GENETIC overexpression , *STATISTICAL correlation - Abstract
Overexpression of tissue factor (TF) has been associated with increased tumor growth, tumor angiogenesis, and metastatic potential in many malignancies, including pancreatic cancer. Additionally, high TF expression was shown to strongly correlate with poor prognoses and decreased survival in pancreatic cancer patients. Herein, we exploited the potential targeting of TF for positron emission tomography (PET) imaging of pancreatic cancer. The TF-targeted tracer was developed through radiolabeling of the anti-human TF monoclonal antibody (ALT-836) with 89 Zr. The tracer was characterized by fluorescence microscopy and flow cytometry assays in BXPC-3 and PANC-1 cells, two pancreatic cancer cell lines with high and low TF expression levels, respectively. Non-invasive PET scans were acquired in tumor-bearing mice injected with 89 Zr-Df-ALT-836. Additionally, ex vivo biodistribution, blocking, and histological studies were performed to establish the affinity and specificity of 89 Zr-Df-ALT-836 for TF in vivo . 89 Zr-labeling of Df-ALT-836 was achieved in high yield and good specific activity. Flow cytometry and microscopy studies revealed no detectable difference in TF-binding affinity between ALT-836 and Df-ALT-836 in vitro . Longitudinal PET scans unveiled a lasting and prominent 89 Zr-Df-ALT-836 uptake in BXPC-3 tumors (peak at 31.5 ± 6.0%ID/g at 48 h post-injection; n = 3), which was significantly abrogated (2.3 ± 0.5%ID/g at 48 h post-injection; n = 3) when mice were pre-injected with a blocking dose (50 mg/kg) of unlabeled ALT-836. Ex vivo biodistribution data confirmed the accuracy of the PET results, and histological analysis correlated high tumor uptake with in situ TF expression. Taken together, these results attest to the excellent affinity and TF-specificity of 89 Zr-Df-ALT-836. With elevated, persistent, and specific accumulation in TF-positive BXPC-3 tumors, PET imaging using 89 Zr-Df-ALT-836 promises to open new avenues for improving future diagnosis, stratification, and treatment response assessment in pancreatic cancer patients. [ABSTRACT FROM AUTHOR]
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- 2017
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14. VEGFR targeting leads to significantly enhanced tumor uptake of nanographene oxide in vivo.
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Shi, Sixiang, Yang, Kai, Hong, Hao, Chen, Feng, Valdovinos, Hector F., Goel, Shreya, Barnhart, Todd E., Liu, Zhuang, and Cai, Weibo
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VASCULAR endothelial growth factors , *TARGETED drug delivery , *GRAPHENE oxide , *TUMOR treatment , *NANOSTRUCTURED materials , *POSITRON emission tomography - Abstract
Although graphene oxide (GO) has recently been considered as a highly attractive nanomaterial for future cancer imaging and therapy, it is still a major challenge to improve its in vivo tumor active targeting efficiency. Here in this full article, we demonstrated the successful and significantly enhanced in vivo tumor vasculature targeting efficacy of well-functionalized GO nanoconjugates by using vascular endothelial growth factor 121 (VEGF121) as the targeting ligand. As-developed GO nanoconjugate exhibits excellent in vivo stability, specific in vitro and in vivo vascular endothelial growth factor receptor (VEGFR) targeting, significantly enhanced tumor accumulation (>8 %ID/g) as well as high tumor-to-muscle contrast, showing great potential for future tumor targeted imaging and therapy. [ABSTRACT FROM AUTHOR]
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- 2015
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15. Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles.
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Guo, Jintang, Hong, Hao, Chen, Guojun, Shi, Sixiang, Zheng, Qifeng, Zhang, Yin, Theuer, Charles P., Barnhart, Todd E., Cai, Weibo, and Gong, Shaoqin
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DRUG delivery systems , *MICELLES , *RADIOACTIVE tracers , *BLOCK copolymers , *AMPHIPHILES , *DENDRITIC cells , *ENDOTHELIAL cells - Abstract
Abstract: Unimolecular micelles formed by dendritic amphiphilic block copolymers poly(amidoamine)–poly(l-lactide)-b-poly(ethylene glycol) conjugated with anti-CD105 monoclonal antibody (TRC105) and 1,4,7-triazacyclononane-N, N′, N-triacetic acid (NOTA, a macrocyclic chelator for 64Cu) (abbreviated as PAMAM–PLA-b-PEG–TRC105) were synthesized and characterized. Doxorubicin (DOX), a model anti-cancer drug, was loaded into the hydrophobic core of the unimolecular micelles formed by PAMAM and PLA via physical encapsulation. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. TRC105-conjugated unimolecular micelles showed a CD105-associated cellular uptake in human umbilical vein endothelial cells (HUVEC) compared with non-targeted unimolecular micelles, which was further validated by cellular uptake in CD105-negative MCF-7 cells. In 4T1 murine breast tumor-bearing mice, 64Cu-labeled targeted micelles exhibited a much higher level of tumor accumulation than 64Cu-labeled non-targeted micelles, measured by serial non-invasive positron emission tomography (PET) imaging and confirmed by biodistribution studies. These unimolecular micelles formed by dendritic amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics. [Copyright &y& Elsevier]
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- 2013
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16. Tumor vasculature targeting and imaging in living mice with reduced graphene oxide
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Shi, Sixiang, Yang, Kai, Hong, Hao, Valdovinos, Hector F., Nayak, Tapas R., Zhang, Yin, Theuer, Charles P., Barnhart, Todd E., Liu, Zhuang, and Cai, Weibo
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TUMOR treatment , *BLOOD vessels , *TARGETED drug delivery , *LABORATORY mice , *GRAPHENE , *NANOSTRUCTURED materials , *POSITRON emission tomography - Abstract
Abstract: Graphene-based nanomaterials have attracted tremendous attention in the field of biomedicine due to their intriguing properties. Herein, we report tumor vasculature targeting and imaging in living mice using reduced graphene oxide (RGO), which was conjugated to the anti-CD105 antibody TRC105. The RGO conjugate, 64Cu–NOTA–RGO–TRC105, exhibited excellent stability in vitro and in vivo. Serial positron emission tomography (PET) imaging studies non-invasively assessed the pharmacokinetics and demonstrated specific targeting of 64Cu–NOTA–RGO–TRC105 to 4T1 murine breast tumors in vivo, compared to non-targeted RGO conjugate (64Cu–NOTA–RGO). In vivo (e.g., blocking 4T1 tumor uptake with excess TRC105), in vitro (e.g., flow cytometry), and ex vivo (e.g., histology) experiments confirmed the specificity of 64Cu–NOTA–RGO–TRC105 for tumor vascular CD105. Since RGO exhibits desirable properties for photothermal therapy, the tumor-specific RGO conjugate developed in this work may serve as a promising theranostic agent that integrates imaging and therapeutic components. [Copyright &y& Elsevier]
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- 2013
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17. In vivo targeting and positron emission tomography imaging of tumor vasculature with 66Ga-labeled nano-graphene
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Hong, Hao, Zhang, Yin, Engle, Jonathan W., Nayak, Tapas R., Theuer, Charles P., Nickles, Robert J., Barnhart, Todd E., and Cai, Weibo
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IMAGING of cancer , *POSITRON emission tomography , *GRAPHENE , *NANOSTRUCTURED materials , *GALLIUM , *TARGETED drug delivery , *ANIMAL models of cancer , *PHARMACOKINETICS - Abstract
Abstract: The goal of this study was to employ nano-graphene for tumor targeting in an animal tumor model, and quantitatively evaluate the pharmacokinetics and tumor targeting efficacy through positron emission tomography (PET) imaging using 66Ga as the radiolabel. Nano-graphene oxide (GO) sheets with covalently linked, amino group-terminated six-arm branched polyethylene glycol (PEG; 10 kDa) chains were conjugated to NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid, for 66Ga-labeling) and TRC105 (an antibody that binds to CD105). Flow cytometry analyses, size measurements, and serum stability studies were performed to characterize the GO conjugates before in vivo investigations in 4T1 murine breast tumor-bearing mice, which were further validated by histology. TRC105-conjugated GO was specific for CD105 in cell culture. 66Ga-NOTA-GO-TRC105 and 66Ga-NOTA-GO exhibited excellent stability in complete mouse serum. In 4T1 tumor-bearing mice, these GO conjugates were primarily cleared through the hepatobiliary pathway. 66Ga-NOTA-GO-TRC105 accumulated quickly in the 4T1 tumors and tumor uptake remained stable over time (3.8 ± 0.4, 4.5 ± 0.4, 5.8 ± 0.3, and 4.5 ± 0.4 %ID/g at 0.5, 3, 7, and 24 h post-injection respectively; n = 4). Blocking studies with unconjugated TRC105 confirmed CD105 specificity of 66Ga-NOTA-GO-TRC105, which was corroborated by biodistribution and histology studies. Furthermore, histological examination revealed that targeting of NOTA-GO-TRC105 is tumor vasculature CD105 specific with little extravasation. Successful demonstration of in vivo tumor targeting with GO, along with the versatile chemistry of graphene-based nanomaterials, makes them suitable nanoplatforms for future biomedical research such as cancer theranostics. [Copyright &y& Elsevier]
- Published
- 2012
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18. Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging
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Xiao, Yuling, Hong, Hao, Javadi, Alireza, Engle, Jonathan W., Xu, Wenjin, Yang, Yunan, Zhang, Yin, Barnhart, Todd E., Cai, Weibo, and Gong, Shaoqin
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MICELLES , *DRUG delivery systems , *POSITRON emission tomography , *COPOLYMERS , *LABORATORY mice , *PEPTIDES , *INTEGRINS - Abstract
Abstract: A multifunctional unimolecular micelle made of a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for cancer-targeted drug delivery and non-invasive positron emission tomography (PET) imaging in tumor-bearing mice. The hyperbranched amphiphilic block copolymer, Boltorn® H40-poly(L-glutamate-hydrazone-doxorubicin)-b-poly(ethylene glycol) (i.e., H40-P(LG-Hyd-DOX)-b-PEG), was conjugated with cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides (cRGD, for integrin αvβ3 targeting) and macrocyclic chelators (1,4,7-triazacyclononane-N, N’, N’’-triacetic acid [NOTA], for 64Cu-labeling and PET imaging) (i.e., H40-P(LG-Hyd-DOX)-b-PEG-OCH3/cRGD/NOTA, also referred to as H40-DOX-cRGD). The anti-cancer drug, doxorubicin (DOX) was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms (i.e., PLG) via a pH-labile hydrazone linkage to enable pH-controlled drug release. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. cRGD-conjugated unimolecular micelles (i.e., H40-DOX-cRGD) exhibited a much higher cellular uptake in U87MG human glioblastoma cells due to integrin αvβ3-mediated endocytosis than non-targeted unimolecular micelles (i.e., H40-DOX), thereby leading to a significantly higher cytotoxicity. In U87MG tumor-bearing mice, H40-DOX-cRGD-64Cu also exhibited a much higher level of tumor accumulation than H40-DOX-64Cu, measured by non-invasive PET imaging and confirmed by biodistribution studies and ex vivo fluorescence imaging. We believe that unimolecular micelles formed by hyperbranched amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
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