Weibo Cai

University of Wisconsin–Madison, Madison, Wisconsin, United States

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Publications (181)1068.31 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Layered double hydroxide (LDH) nanomaterial has emerged as a novel delivery agent for biomedical applications due to its unique structure and properties. However, in vivo positron emission tomography (PET) imaging with LDH nanoparticles has not been achieved. The aim of this study is to explore chelator-free labeling of LDH nanoparticles with radioisotopes for in vivo PET imaging. Bivalent cation (64)Cu(2+) and trivalent cation (44)Sc(3+) were found to readily label LDH nanoparticles with excellent labeling efficiency and stability, whereas tetravalent cation (89)Zr(4+) could not label LDH since it does not fit into the LDH crystal structure. PET imaging shows that prominent tumor uptake was achieved in 4T1 breast cancer with (64)Cu-LDH-BSA via passive targeting alone (7.7 ± 0.1%ID/g at 16 h post-injection; n = 3). These results support that LDH is a versatile platform that can be labeled with various bivalent and trivalent radiometals without comprising the native properties, highly desirable for PET image-guided drug delivery.
    Scientific Reports 11/2015; 5:16930. DOI:10.1038/srep16930 · 5.58 Impact Factor
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    ABSTRACT: Given the highly heterogeneous character of brain malignancies and the associated implication for its proper diagnosis and treatment, finding biomarkers that better characterize this disease from a molecular standpoint is imperative. In this study, we evaluated CD146 as a potential molecular target for diagnosis and targeted therapy of glioblastoma multiforme (GBM), the most common and lethal brain malignancy. YY146, an anti-CD146 monoclonal antibody, was generated and radiolabeled for noninvasive positron-emission tomography (PET) imaging of orthotopic GBM models. (64)Cu-labeled YY146 preferentially accumulated in the tumors of mice bearing U87MG xenografts, which allowed the acquisition of high-contrast PET images of small tumor nodules (∼2 mm). Additionally, we found that tumor uptake correlated with the levels of CD146 expression in a highly specific manner. We also explored the potential therapeutic effects of YY146 on the cancer stem cell (CSC) and epithelial-to-mesenchymal (EMT) properties of U87MG cells, demonstrating that YY146 can mitigate those aggressive phenotypes. Using YY146 as the primary antibody, we performed histological studies of World Health Organization (WHO) grades I through IV primary gliomas. The positive correlation found between CD146-positive staining and high tumor grade (χ(2) = 9.028; P = 0.029) concurred with the GBM data available in The Cancer Genome Atlas (TCGA) and validated the clinical value of YY146. In addition, we demonstrate that YY146 can be used to detect CD146 in various cancer cell lines and human resected tumor tissues of multiple other tumor types (gastric, ovarian, liver, and lung), indicating a broad applicability of YY146 in solid tumors.
    Proceedings of the National Academy of Sciences 11/2015; DOI:10.1073/pnas.1502648112 · 9.67 Impact Factor
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    ABSTRACT: Objective: Lung cancer accounts for 17% of cancer-related deaths worldwide and most patients present with locally advanced or metastatic disease. Novel positron emission tomography (PET) imaging agents for assessing vascular endothelial growth factor receptor-2 (VEGFR-2) expression can be utilized for detecting VEGFR-2+ malignancies and subsequent monitoring of therapeutic response to VEGFR-2-targeted therapies. Here we report the synthesis and characterization of the antibody-based imaging agent for detection of VEGFR-2 expression in vivo. Methods: Ramucirumab (named RamAb), a fully humanized IgG1 monoclonal antibody, was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu. Flow cytometry analysis and microscopy studies were performed to compare VEGFR-2 binding affinity of RamAb and NOTA-RamAb. PET imaging and biodistribution studies were performed in nude mice bearing HCC4006 and A549 xenograft tumors. Ex vivo histopathology were performed to elucidate the expression patterns of VEGFR-2 in different tissues and organs to validate in vivo results. Results: Flow cytometry examination revealed the specific binding capacity of FITC-RamAb to VEGFR-2 and no difference in VEGFR-2 binding affinity was seen between RamAb and NOTA-RamAb. After labeled with (64)Cu, PET imaging revealed specific and prominent uptake of (64)Cu-NOTA-RamAb in VEGFR-2 positive HCC4006 tumors (9.4 ± 0.5 %ID/g at 48 h post-injection; n = 4) and significantly lower uptake in VEGFR-2 negative A549 tumors (4.3 ± 0.2 %ID/g at 48 h post-injection; n = 3). Blocking experiments revealed significantly lower uptake in HCC4006 tumors, along with histology analysis, further confirming the VEGFR-2 specificity of (64)Cu-NOTA-RamAb. Conclusion: This study provides initial evidence that (64)Cu-NOTA-RamAb can function as a PET imaging agent for visualizing VEGFR-2 expression in vivo, which may also find potential applications in monitoring the treatment response of VEGFR-2 targeted cancer therapy.
    Journal of Nuclear Medicine 11/2015; DOI:10.2967/jnumed.115.166462 · 6.16 Impact Factor
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    ABSTRACT: Tetracarboxylic porphyrins and polyethylene glycol (PEG) diamines were crosslinked in conditions that gave rise to a water-soluble porphyrin polyamide. Using PEG linkers 2 kDa or larger prevented fluorescence self-quenching. This networked porphyrin mesh was retained during dialysis with membranes with a 100 kDa pore size, yet passed through the membrane when centrifugal filtration was applied. Following intravenous administration, the porphyrin mesh, but not the free porphyrin, was rapidly cleared via renal excretion. The process could be monitored by fluorescence analysis of collected urine, with minimal background due to the large Stokes shift of the porphyrin (230 nm separating excitation and emission peaks). In a rhabdomyolysis mouse model of renal failure, porphyrin mesh urinary clearance was significantly impaired. This led to slower accumulation in the bladder, which could be visualized non-invasively via fluorescence imaging. Without further modification, the porphyrin mesh was chelated with (64)Cu for dynamic whole body positron emission tomography imaging of renal clearance. Together, these data show that small porphyrin-PEG polymers can serve as effective multimodal markers of renal function.
    Biomaterials 10/2015; 76:25-32. DOI:10.1016/j.biomaterials.2015.10.049 · 8.56 Impact Factor
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    ABSTRACT: Interleukin-15 (IL-15), a potent stimulant of CD8+ T and NK cells, is a promising cancer immunotherapeutic. ALT-803 is a complex of an IL-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein that was found to exhibit enhanced biologic activity in vivo with a substantially longer serum half-life than recombinant IL-15. A single intravenous dose of ALT-803, but not IL-15, eliminated well-established tumors and prolonged survival of mice bearing multiple myeloma. In this study, we extended these findings to demonstrate the superior antitumor activity of ALT-803 over IL-15 in mice bearing subcutaneous B16F10 melanoma tumors and CT26 colon carcinoma metastases. Tissue biodistribution studies in mice also showed much greater retention of ALT-803 in the lymphoid organs compared to IL-15, consistent with its highly potent immunostimulatory and antitumor activities in vivo. Weekly dosing with 1 mg/kg ALT-803 in C57BL/6 mice was well-tolerated, yet capable of increasing peripheral blood lymphocyte, neutrophil and monocyte counts by >8-fold. ALT-803 dose-dependent stimulation of immune cell infiltration into the lymphoid organs was also observed. Similarly, cynomolgus monkeys treated weekly with ALT-803 showed dose-dependent increases of peripheral blood lymphocyte counts, including NK, CD4+, and CD8+ memory T cell subsets. In vitro studies demonstrated ALT-803-mediated stimulation of mouse and human immune cell proliferation and IFN-γ production without inducing a broad-based release of other proinflammatory cytokines (i.e., cytokine storm). Based on these results, a weekly dosing regimen of ALT-803 has been implemented in multiple clinical studies to evaluate the dose required for effective immune cell stimulation in humans.
    10/2015; DOI:10.1158/2326-6066.CIR-15-0093-T
  • Emily B. Ehlerding · Feng Chen · Weibo Cai ·

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    ABSTRACT: Early diagnosis remains a task of upmost importance for reducing cancer morbidity and mortality. Successful development of highly specific companion diagnostics targeting aberrant molecular pathways of cancer is needed for sensitive detection, accurate diagnosis, and opportune therapeutic intervention. Herein, we generated a bispecific immunoconjugate [denoted as Bs-F(ab)2] by linking two antibody Fab fragments, an anti-epidermal growth factor receptor (EGFR) Fab and an anti-CD105 Fab, via bioorthogonal "click" ligation of trans-cyclooctene and tetrazine. PET imaging of mice bearing U87MG (EGFR/CD105(+/+)) tumors with (64)Cu-labeled Bs-F(ab)2 revealed a significantly enhanced tumor uptake [42.9 ± 9.5 percentage injected dose per gram (%ID/g); n = 4] and tumor-to-background ratio (tumor/muscle ratio of 120.2 ± 44.4 at 36 h postinjection; n = 4) compared with each monospecific Fab tracer. Thus, we demonstrated that dual targeting of EGFR and CD105 provides a synergistic improvement on both affinity and specificity of (64)Cu-NOTA-Bs-F(ab)2. (64)Cu-NOTA-Bs-F(ab)2 was able to visualize small U87MG tumor nodules (<5 mm in diameter), owing to high tumor uptake (31.4 ± 10.8%ID/g at 36 h postinjection) and a tumor/muscle ratio of 76.4 ± 52.3, which provided excellent sensitivity for early detection. Finally, we successfully confirmed the feasibility of a ZW800-1-labeled Bs-F(ab)2 for near-infrared fluorescence imaging and image-guided surgical resection of U87MG tumors. More importantly, our rationale can be used in the construction of other disease-targeting bispecific antibody fragments for early detection and diagnosis of small malignant lesions.
    Proceedings of the National Academy of Sciences 09/2015; 112(41):201509667. DOI:10.1073/pnas.1509667112 · 9.67 Impact Factor
  • Emily B Ehlerding · Weibo Cai ·

    Journal of Nuclear Medicine 09/2015; DOI:10.2967/jnumed.115.166199 · 6.16 Impact Factor
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    ABSTRACT: (52)Mn (t1/2 =5.59 d, ß+ = 29.6%, Eßave = 0.24 MeV) shows promise in positron emission tomography (PET) and in dual-modality manganese-enhanced magnetic resonance imaging (MEMRI) applications including neural tractography, stem cell tracking, and biological toxicity studies. The extension to bioconjugate application requires high specific activity (52)Mn in a state suitable for macromolecule labeling. To that end a (52)Mn production, purification, and labeling system is presented, and its applicability in preclinical, macromolecule PET is shown using the conjugate (52)Mn-DOTA-TRC105. (52)Mn is produced by 60 µA, 16 MeV proton irradiation of natural chromium metal pressed into a silver disc support. Radiochemical separation proceeds by strong anion exchange chromatography of the dissolved Cr target, employing a semi-organic mobile phase, 97:3 (v:v) ethanol: HCl (11M, aqueous). The method is 62 ± 14% efficient (n=7) in (52)Mn recovery, leading to a separation factor from Cr of (1.6 ± 1.0) x10(6) (n = 4), and an average effective specific activity of 0.8 GBq/µmol (n = 4) in titration against DOTA. (52)Mn-DOTA-TRC105 conjugation and labeling demonstrate the potential for chelation applications. In vivo images acquired using PET/CT in mice bearing 4T1 xenograft tumors are presented. Peak tumor uptake is 18.7 ± 2.7 %ID/g at 24 hours post injection and ex vivo (52)Mn biodistribution validates the in vivo PET data. Free (52)Mn(2+)(as chloride or acetate) is used as a control in additional mice to evaluate the non-targeted biodistribution in the tumor model.
    Bioconjugate Chemistry 08/2015; DOI:10.1021/acs.bioconjchem.5b00414 · 4.51 Impact Factor
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    ABSTRACT: Traditional chelator-based radio-labeled nanoparticles and positron emission tomography (PET) imaging are playing vital roles in the field of nano-oncology. However, their long-term in vivo integrity and potential mismatch of the biodistribution patterns between nanoparticle and radioisotope are two major concerns for this approach. Here, we present a chelator-free zirconium-89 (89Zr, t1/2=78.4 h) labeling of mesoporous silica nanoparticle (MSN) with significantly enhanced in vivo long-term (>20 Days) stability. Successful radio-labeling and in vivo stability are demonstrated to be highly dependent on both the concentration and location of deprotonated silanol groups (-Si-O-) from two types of silica nanoparticles investigated. This work reports on 89Zr-labeled MSN with detailed labeling mechanism investigation and long-term stability study. With its attractive radio-stability and the simplicity of chelator-free radio-labeling, 89Zr-MSN offers a novel, simple, and accurate way for studying the in vivo long-term fate and PET image-guided drug delivery of MSN in the near future.
    ACS Nano 07/2015; 9(8). DOI:10.1021/acsnano.5b00526 · 12.88 Impact Factor
  • Sarah Yang · Shreya Goel · Weibo Cai ·

    Biological and Pharmaceutical Applications of Nanomaterials, 07/2015: pages 319-346; , ISBN: 978-1-4822-5016-9
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    Shreya Goel · Feng Chen · Weibo Cai ·

    Nanomedicine 06/2015; 10(11):1681-3. DOI:10.2217/nnm.15.63 · 5.41 Impact Factor
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    ABSTRACT: Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin αvβ3, may offer advantages in image contrast, time for imaging, and low uptake in nontarget tissues. Two cyclic RGDfK derivatives, (PEG)2-c(RGDfK) and PEG4-SAA4-c(RGDfK), were constructed and conjugated to NOTA for (64)Cu labeling. Their integrin αvβ3-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the (64)Cu-labeled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h after injection. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers. The IC50 values of NOTA-(PEG)2-c(RGDfK) and NOTA-PEG4-SAA4-c(RGDfK) were 444 ± 41 nM and 288 ± 66 nM, respectively. Dynamic PET data of (64)Cu-NOTA-(PEG)2-c(RGDfK) and (64)Cu-NOTA-PEG4-SAA4-c(RGDfK) showed similar circulation t 1/2 and peak tumor uptake of about 4 %ID/g for both tracers. Due to its marked hydrophilicity, (64)Cu-NOTA-PEG4-SAA4-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintained excellent tumor-to-background ratios. Static PET scans at later time-points corroborated the enhanced excretion of the tracer, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the integrin αvβ3-specificity of the peptides. Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed fast, high-contrast PET imaging of tumor-associated integrin αvβ3. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake.
    European Journal of Nuclear Medicine 05/2015; 42(12). DOI:10.1007/s00259-015-3085-7 · 5.38 Impact Factor
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    Christopher G England · Haiming Luo · Weibo Cai ·
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    ABSTRACT: Exploration of protein function and interaction is critical for discovering links between genomics, proteomics, and disease state; yet the immense complexity of proteomics found in biological systems currently limit our investigational capacities. While affinity and auto-fluorescent tags are widely employed for protein analysis, these methods have limited success as they lack specificity and require multiple fusion tags and genetic constructs. As an alternative approach, the innovative HaloTag protein fusion platform allows for comprehensive analysis of protein function and interaction using a single genetic construct with multiple capabilities. This is accomplished using a simplified process, in which a variable HaloTag ligand binds rapidly to the HaloTag protein (usually linked to the protein of interest) with high affinity and specificity. In this review article, we examine all current applications of the HaloTag technology platform for biomedical applications such as the study of protein isolation and purification, protein function, protein-protein and protein-DNA interactions, biological assays, in vitro cellular imaging, and in vivo molecular imaging. In addition, novel uses of the HaloTag platform are briefly discussed with potential future applications.
    Bioconjugate Chemistry 05/2015; 26(6). DOI:10.1021/acs.bioconjchem.5b00191 · 4.51 Impact Factor
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    ABSTRACT: The critical challenge in abdominal aortic aneurysm (AAA) research is the accurate diagnosis and assessment of AAA progression. Angiogenesis is a pathological hallmark of AAA, and CD105 is highly expressed on newly formed vessels. Our goal was to use (64)Cu-labeled anti-CD105 antibody Fab fragment for noninvasive assessment of angiogenesis in the aortic wall in a murine model of AAA. Fab fragment of TRC105, a mAb that specifically binds to CD105, was generated by enzymatic papain digestion and conjugated to NOTA for (64)Cu-labeling. Binding affinity/specificity of NOTA-TRC105-Fab was evaluated by flow cytometry and various ex vivo studies. BALB/c mice were anesthetized and treated with calcium phosphate to induce AAA, which underwent weekly PET scans using (64)Cu-NOTA-TRC105-Fab. Biodistribution and autoradiography studies were also performed to confirm the accuracy of PET results. NOTA-TRC105-Fab exhibited high purity and specifically bound to CD105 in vitro. Uptake of (64)Cu-NOTA-TRC105-Fab increased from a control level of 3.4 ± 0.1 to 9.5 ± 0.4 %ID/g at 6 h p.i. on Day 5, and decreased to 7.2 ± 1.4 %ID/g on Day 12 which correlated well with biodistribution and autoradiography studies (i.e. much higher tracer uptake in AAA than normal aorta). Of note, enhanced AAA contrast was achieved, due to the minimal background in the abdominal area of mice. Degradation of elastic fibers and highly expressed CD105 were observed in ex vivo studies. (64)Cu-NOTA-TRC105-Fab cleared rapidly through kidneys, which enabled noninvasive PET imaging of the aorta with enhanced contrast and showed increased angiogenesis (CD105 expression) during AAA. (64)Cu-NOTA-TRC105-Fab PET may potentially be used for future diagnosis and prognosis of AAA. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 04/2015; 56(6). DOI:10.2967/jnumed.114.153098 · 6.16 Impact Factor
  • Casey A Dougherty · Weibo Cai · Hao Hong ·
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    ABSTRACT: Aptamers are single-stranded oligonucleotides with high affinity and specificity to the target molecules or cells, thus they can serve as an important category of molecular targeting ligand. Since their discovery, aptamers have been rapidly translated into clinical practice. The strong target affinity/selectivity, cost-effectivity, chemical versatility and safety of aptamers are superior to traditional peptides- or proteins-based ligands which make them unique choices for molecular imaging. Therefore, aptamers are considered to be extremely useful to guide various imaging contrast agents to the target tissues or cells for optical, magnetic resonance, nuclear, computed tomography, ultrasound and multimodality imaging. This review aims to provide an overview of aptamers' advantages as targeting ligands and their application in targeted imaging. Further research in synthesis of new types of aptamers and their conjugation with new categories of contrast agents is required to develop clinically translatable aptamer-based imaging agents which will eventually result in improved patient care.
    Current topics in medicinal chemistry 04/2015; 15(12). DOI:10.2174/1568026615666150413153400 · 3.40 Impact Factor
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    ABSTRACT: Actively targeted theranostic nanomedicine may be the key for future personalized cancer management. Although numerous types of theranostic nanoparticles have been developed in the last decade for cancer treatment, challenges still exist in the engineering of biocompatible theranostic nanoparticles with highly specific in vivo tumor targeting capabilities. Here, we report the design, synthesis, surface engineering, and in vivo active vasculature targeting of a new category of theranostic nanoparticle for future cancer management. Water-soluble photothermally sensitive copper sulfide nanoparticles were encapsulated in biocompatible mesoporous silica shells, followed by multi-step surface engineering to form the final theranostic nanoparticle. Systematic in vitro targeting, an in vivo long-term toxicity study, photothermal ablation evaluation, in vivo vasculature targeted imaging, and biodistribution and histology studies were performed to fully explore the potential of these as-developed new theranostic nanoparticles.
    ACS Nano 04/2015; 9(4). DOI:10.1021/nn507241v · 12.88 Impact Factor
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    ABSTRACT: The hepatocyte growth factor (HGF) and its receptor, c-Met, are actively involved in tumor progression/metastasis and associated closely with poor prognostic outcome of cancer patients. Thus developing positron emission tomography (PET) agents for assessing c-Met expression would be extremely useful for diagnosis of cancer and subsequent monitoring of responses to c-Met-targeted therapies. Here we report the characterization of recombinant human hepatocyte growth factor (rh-HGF) as a PET tracer for detection of c-Met expression in vivo. rh-HGF was expressed in human embryonic kidney (HEK) 293 cells and purified by nickel-nitrilogriacetic acid (Ni-NTA) affinity chromatography. The concentrated rh-HGF was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu. c-Met binding evaluation by flow cytometry was performed in both U87MG and MDA-MB-231 cell lines, which have high and low level of c-Met, respectively. PET imaging and biodistribution studies were performed in nude mice bearing U87MG and MDA-MB-231 xenografted tumors. The rh-HGF expression yield was 150-200 μg protein per 5 × 106 cells after 48 h transfection with purity of 85% ~ 90%. Flow cytometry examination confirmed strong and specific binding capacity of rh-HGF to c-Met. After labeled with (64)Cu, PET imaging revealed specific and prominent uptake of (64)Cu-NOTA-rh-HGF in c-Met positive U87MG tumors (6.7 ± 1.8 %ID/g at 9 h post-injection) and significantly lower uptake in c-Met negative MDA-MB-231 tumors (1.8 ± 0.6 %ID/g at 9 h post-injection). The fact that heat-denatured rh-HGF (termed as dnrh-HGF) had significantly lower uptake in U87MG tumors, along with histology analysis, confirmed the c-Met specificity of (64)Cu-NOTA-rh-HGF. The study provided the initial evidence to confirm that (64)Cu-NOTA-rh-HGF is applicable for visualizing c-Met expression in vivo, which may also find potential applications in treatment monitoring of c-Met-targeted cancer therapy. Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
    Journal of Nuclear Medicine 04/2015; 56(5). DOI:10.2967/jnumed.115.154690 · 6.16 Impact Factor
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    ABSTRACT: Development of multifunctional and well-dispersed hollow mesoporous silica nanoparticles (HMSNs) for tumor vasculature targeted drug delivery and PET imaging. Amine functionalized HMSNs (150-250 nm) were conjugated with a macrocyclic chelator, (S)-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triaceticacid (NOTA), PEGylated and loaded with antiangiogenesis drug, Sunitinib. Cyclo(Arg-Gly-Asp-D-Tyr-Lys) (cRGDyK) peptide was attached to the nanoconjugate and radiolabeled with (64)Cu for PET imaging. (64)Cu-NOTA-HMSN-PEG-cRGDyK exhibited integrin-specific uptake both in vitro and in vivo. PET results indicated approximately 8% ID/g uptake of targeted nanoconjugates in U87MG tumors, which correlated well with ex vivo and histological analyses. Enhanced tumor-targeted delivery of sunitinib was also observed. We successfully developed tumor vasculature targeted HMSNs for PET imaging and image-guided drug delivery.
    Nanomedicine 04/2015; 10(8):1233-46. DOI:10.2217/nnm.14.226 · 5.41 Impact Factor
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    ABSTRACT: To date, there is no effective therapy for triple-negative breast cancer (TNBC), which has a dismal clinical outcome. Upregulation of tissue factor (TF) expression leads to increased patient morbidity and mortality in many solid tumor types, including TNBC. Our goal was to employ the Fab fragment of ALT-836, a chimeric anti-human TF mAb, for PET imaging of TNBC, which can be used to guide future TNBC therapy. ALT-836-Fab was generated by enzymatic papain digestion. SDS-PAGE and FACS studies were performed to evaluate the integrity and TF binding affinity of ALT-836-Fab before NOTA conjugation and (64)Cu-labeling. Serial PET imaging and biodistribution studies were carried out to evaluate the tumor targeting efficacy and pharmacokinetics in the MDA-MB-231 TNBC model, which expresses high levels of TF on the tumor cells. Blocking studies, histological assessment, as well as RT-PCR were performed to confirm TF specificity of (64)Cu-NOTA-ALT-836-Fab. ALT-836-Fab was produced with high purity, which exhibited superb TF binding affinity and specificity. Serial PET imaging revealed rapid and persistent tumor uptake of (64)Cu-NOTA-ALT-836-Fab (5.1 ± 0.5 %ID/g at 24 h post-injection; n = 4) and high tumor/muscle ratio (7.0 ± 1.2 at 24 h post-injection; n = 4), several-fold higher than that of the blocking group and tumor models that do not express significant level of TF, which was confirmed by biodistribution studies. TF specificity of the tracer was also validated by histology and RT-PCR. (64)Cu-NOTA-ALT-836-Fab exhibited prominent tissue factor targeting efficiency in MDA-MB-231 TNBC model. The use of a Fab fragment led to fast tumor uptake and good tissue/muscle ratio, which may be translated into same-day immunoPET imaging in the clinical setting to improve TNBC patient management.
    European Journal of Nuclear Medicine 03/2015; 42(8). DOI:10.1007/s00259-015-3038-1 · 5.38 Impact Factor

Publication Stats

8k Citations
1,068.31 Total Impact Points


  • 2008-2015
    • University of Wisconsin–Madison
      • • Department of Medical Physics
      • • Department of Radiology
      • • School of Medicine and Public Health
      Madison, Wisconsin, United States
  • 2012
    • University of Wisconsin - Stout
      Menominee, Wisconsin, United States
  • 2006-2009
    • Stanford University
      • • Department of Medicine
      • • Department of Radiology
      Palo Alto, California, United States
  • 2006-2008
    • Stanford Medicine
      • • Department of Radiology
      • • Department of Neurosurgery
      Stanford, California, United States