Weibo Cai

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

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Publications (145)716.48 Total impact

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    ABSTRACT: Intrinsically radiolabeled nanoparticles are an emerging paradigm for nanotechnology and nanomedicine. On page 3825, F. Chen, W. Cai, and co-workers summarize the state-of-the-art techniques for the preparation of intrinsically radiolabeled nanoparticles, with a focus on the formation mechanism, in vivo stability, and multimodality molecular imaging.
    Small 10/2014; 10(19). · 7.82 Impact Factor
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    ABSTRACT: Tremendous resources are being invested all over the world for prevention, diagnosis, and treatment of various types of cancer. Successful cancer management depends on accurate diagnosis of the disease along with precise therapeutic protocol. The conventional systemic drug delivery approaches generally cannot completely remove the competent cancer cells without surpassing the toxicity limits to normal tissues. Therefore, development of efficient drug delivery systems holds prime importance in medicine and healthcare. Also, molecular imaging can play an increasingly important and revolutionizing role in disease management. Synergistic use of molecular imaging and targeted drug delivery approaches provides unique opportunities in a relatively new area called 'image-guided drug delivery' (IGDD). Single-photon emission computed tomography (SPECT) is the most widely used nuclear imaging modality in clinical context and is increasingly being used to guide targeted therapeutics. The innovations in material science have fueled the development of efficient drug carriers based on, polymers, liposomes, micelles, dendrimers, microparticles, nanoparticles, etc. Efficient utilization of these drug carriers along with SPECT imaging technology have the potential to transform patient care by personalizing therapy to the individual patient, lessening the invasiveness of conventional treatment procedures and rapidly monitoring the therapeutic efficacy. SPECT-IGDD is not only effective for treatment of cancer but might also find utility in management of several other diseases. Herein, we provide a concise overview of the latest advances in SPECT-IGDD procedures and discuss the challenges and opportunities for advancement of the field.
    Current drug targets. 09/2014;
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    ABSTRACT: Insulin-like growth factor 1 receptor (IGF1R) plays an important role in proliferation, apoptosis, angiogenesis, and tumor invasion. The expression level of IGF1R is related to resistance to several targeted therapies. The goal of this study was to develop an immunoPET tracer for imaging of IGF1R in prostate cancer. Murine antibodies against human IGF1R were generated in BALB/c mice, which were screened in IGF1R-positive MCF-7 cells using flow cytometry as well as biodistribution studies with multiple 64Cu-labeled antibody clones. The antibody production method we adopted could readily produce milligram quantities of anti-IGF1R antibodies for in vivo studies. One antibody clone (1A2G11) with the highest affinity for IGF1R was selected and conjugated to NOTA for 64Cu-labeling. NOTA-1A2G11 maintained IGF1R specificity/avidity based on flow cytometry. 64Cu-labeling was achieved with good yield (>50%) and high specific activity (> 1 Ci/μmol). Serial PET imaging revealed that uptake of 64Cu-NOTA-1A2G11 was 2.8 ± 0.7, 10.2 ± 2.6, and 9.6 ± 1.7 %ID/g in IGF1R-positive DU-145 tumors at 4, 24, and 48 h post-injection, respectively (n = 3), significantly higher than that in IGF1R-negative LNCaP tumors (< 3%ID/g at each time point) except at 4 h post-injection. Histology studies showed strong correlations between IGF1R expression level in the prostate cancer tumor tissues and tumor uptake of 64Cu-NOTA-1A2G11. Prominent, persistent, and IGF1R-specific uptake of 64Cu-NOTA-1A2G11 in IGF1R-positive prostate tumors holds strong potential for future cancer diagnosis, prognosis, and therapy using this antibody.
    Molecular Pharmaceutics 08/2014; · 4.57 Impact Factor
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    ABSTRACT: Graphene-based nanomaterials have attracted tremendous interest over the last decade due to their unique electronic, optical, mechanical and chemical properties. However, the biomedical applications of these intriguing nanomaterials are still limited due to their suboptimal solubility/biocompatibility, potential toxicity, and difficulties in achieving active tumor targeting, just to name a few. In this review article, we will discuss in detail the important role of surface engineering (i.e. bioconjugation) in improving the in vitro/in vivo stability and enriching the functionality of graphene-based nanomaterials, which can enable single-/multi-modality imaging (e.g. optical imaging, positron emission tomography, magnetic resonance imaging) and therapy (e.g. photothermal therapy, photodynamic therapy, and drug/gene delivery) of cancer. Current challenges and future research directions are also discussed and we believe that graphene-based nanomaterials are attractive nanoplatforms for a broad array of future biomedical applications.
    Bioconjugate Chemistry 08/2014; · 4.58 Impact Factor
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    ABSTRACT: Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients.
    Advanced drug delivery reviews. 07/2014;
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    ABSTRACT: The overexpression of integrin αvβ3 has been linked to tumor aggressiveness and metastasis in several cancer types. Because of its high affinity, peptides containing the arginine-glycine-aspartic acid (RGD) motif have been proven valuable vectors for noninvasive imaging of integrin αvβ3 expression and for targeted radionuclide therapy. In this study, we aim to develop a (44)Sc-labeled RGD-based peptide for in vivo positron emission tomography (PET) imaging of integrin αvβ3 expression in a preclinical cancer model. High quality (44)Sc (t1/2, 3.97 h; β(+) branching ratio, 94.3%) was produced inexpensively in a cyclotron, via proton irradiation of natural Ca metal targets, and separated by extraction chromatography. A dimeric cyclic-RGD peptide, (cRGD)2, was conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with (44)Sc in high yield (>90%) and specific activity (7.4 MBq/nmol). Serial PET imaging of mice bearing U87MG tumor xenografts showed elevated (44)Sc-DOTA-(cRGD)2 uptake in the tumor tissue of 3.93 ± 1.19, 3.07 ± 1.17, and 3.00 ± 1.25 %ID/g at 0.5, 2, and 4 h postinjection, respectively (n = 3), which were validated by ex vivo biodistribution experiments. The integrin αvβ3 specificity of the tracer was corroborated, both in vitro and in vivo, by competitive cell binding and receptor blocking assays. These results parallel previously reported studies showing similar tumor targeting and pharmacokinetic profiles for dimeric cRGD peptides labeled with (64)Cu or (68)Ga. Our findings, together with the advantageous radionuclidic properties of (44)Sc, capitalize on the relevance of this isotope as an attractive alternative isotope to more established radiometals for small molecule-based PET imaging, and as imaging surrogate of (47)Sc in theranostic applications.
    Molecular Pharmaceutics 07/2014; · 4.57 Impact Factor
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    ABSTRACT: There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and provide good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ∼20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1,000). Unlike conventional chromophores, nanonaps exhibit non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole-body imaging.
    Nature Nanotechnology 07/2014; · 31.17 Impact Factor
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    ABSTRACT: Intrinsically germanium-69-labeled super-paramagnetic iron oxide nanoparticles are synthesized via a newly developed, fast and highly specific chelator-free approach. The biodistribution pattern and the feasibility of (69) Ge-SPION@PEG for in vivo dual-modality positron emission tomography/magnetic resonance (PET/MR) imaging and lymph-node mapping are investigated, which represents the first example of the successful utilization of a (69) Ge-based agent for PET/MR imaging.
    Advanced Materials 06/2014; · 14.83 Impact Factor
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    ABSTRACT: Multifunctional mesoporous silica nanoparticles (MSN) with well-integrated multimodality imaging properties have generated increasing research interest in the last decade. However, limited progress has been made in developing MSN-based multimodality imaging agents to image tumors. We describe the successful conjugation of, copper-64 (64Cu, t1/2=12.7 h), 800CW (a near-infrared fluorescence [NIRF] dye) and TRC105 (a human/murine chimeric IgG1 monoclonal antibody) to the surface of MSN via well-developed surface engineering procedures, resulting in a dual-labeled MSN for in vivo targeted positron emission tomography (PET) imaging/NIRF imaging of the tumor vasculature. Pharmacokinetics and tumor targeting efficacy/specificity in 4T1 murine breast tumor-bearing mice were thoroughly investigated through various in vitro, in vivo, and ex vivo experiments. Dual-labeled MSN is an attractive candidate for future cancer theranostics.
    Molecular Pharmaceutics 06/2014; · 4.57 Impact Factor
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    ABSTRACT: Although chelator-based radiolabeling techniques have been used for decades, concerns about the complexity of coordination chemistry, possible altering of pharmacokinetics of carriers, and potential detachment of radioisotopes during imaging have driven the need for developing a simple yet better technique for future radiolabeling. Here, the emerging concept of intrinsically radiolabeled nanoparticles, which could be synthesized using methods such as hot-plus-cold precursors, specific trapping, cation exchange, and proton beam activation, is introduced. Representative examples of using these multifunctional nanoparticles for multimodality molecular imaging are highlighted together with current challenges and future research directions. Although still in the early stages, design and synthesis of intrinsically radiolabeled nanoparticles has shown attractive potential to offer easier, faster, and more specific radiolabeling possibilities for the next generation of molecular imaging.
    Small 06/2014; · 7.82 Impact Factor
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    ABSTRACT: Positron emission tomography (PET) is an important modality in the field of molecular imaging which is gradually impacting patient care by providing safe, fast and reliable techniques that help to alter the course of patient care by revealing invasive, de-facto procedures to be unnecessary or rendering them obsolete. Also, PET provides a key connection between the molecular mechanisms involved in the pathophysiology of disease and the according targeted therapies. Recently, PET imaging is also gaining ground in the field of drug delivery. Current drug delivery research is focused on developing novel drug delivery systems with emphasis on precise targeting, accurate dose delivery and minimal toxicity in order to achieve maximum therapeutic efficacy. At the intersection between PET imaging and controlled drug delivery, interest has grown in combining both these paradigms into clinically effective formulations. PET image-guided drug delivery has great potential to revolutionize patient care by in vivo assessment of drug biodistribution and accumulation at the target site and real-time monitoring of the therapeutic outcome. The expected end-point of this approach is to provide a fundamental support for the optimization of innovative diagnostic and therapeutic strategies that could contribute to emerging concepts in the field of "personalized medicine". This review focuses on the recent developments in PET image-guided drug delivery and discusses intriguing opportunities for future development. The preclinical data reported to date are quite promising, and it is evident that such strategies in cancer management holds promise for clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in enhanced quality of life for cancer patients.
    Molecular Pharmaceutics 05/2014; · 4.57 Impact Factor
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    ABSTRACT: Ligand-based molecular imaging probes have been designed with high affinity and specificity for monitoring biological process and responses. Single target recognition by traditional probes can limit their applicability for disease detection and therapy as synergistic action between disease mediators and different receptors are often involved in disease progression. Consequently, probes that can recognize multiple targets should demonstrate higher targeting efficacy and specificity than their mono-specific peers. This concept has been validated by multiple bispecific heterodimer-based imaging probes with promising results in several animal models. This review summarizes the design strategies for bispecific peptide and antibody-based heterodimers and their applications in molecular targeting and imaging. The design and application of bispecific heterodimer-conjugated nanomaterials are also discussed.
    Molecular Pharmaceutics 04/2014; · 4.57 Impact Factor
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    ABSTRACT: Brush-shaped amphiphilic block copolymers were conjugated with a monoclonal antibody against CD105 (i.e., TRC105) and a macrocyclic chelator for (64)Cu-labeling to generate multifunctional theranostic unimolecular micelles. The backbone of the brush-shaped amphiphilic block copolymer was poly(2-hydroxyethyl methacrylate) (PHEMA) and the side chains were poly(l-lactide)-poly(ethylene glycol) (PLLA-PEG). The doxorubicin (DOX)-loaded unimolecular micelles showed a pH-dependent drug release profile and a uniform size distribution. A significantly higher cellular uptake of TRC105-conjugated micelles was observed in CD105-positive human umbilical vein endothelial cells (HUVEC) than nontargeted micelles due to CD105-mediated endocytosis. In contrast, similar and extremely low cellular uptake of both targeted and nontargeted micelles was observed in MCF-7 human breast cancer cells (CD105-negative). The difference between the in vivo tumor accumulation of (64)Cu-labeled TRC105-conjugated micelles and that of nontargeted micelles was studied in 4T1 murine breast tumor-bearing mice, by serial positron emission tomography (PET) imaging and validated by biodistribution studies. These multifunctional unimolecular micelles offer pH-responsive drug release, noninvasive PET imaging capability, together with both passive and active tumor-targeting abilities, thus making them a desirable nanoplatform for cancer theranostics.
    ACS Applied Materials & Interfaces 03/2014; · 5.90 Impact Factor
  • Feng Chen, Weibo Cai
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    ABSTRACT: The last decade has witnessed an unprecedented expansion in the design, synthesis and preclinical applications of various multifunctional nanomaterials. Efficient targeting of these nanomaterials to the tumor site is critical for delivering sufficient amount of anti-cancer drugs to suppress tumor growth, while avoiding undesired side effects. Although some nanoparticles could accumulate in the tumor tissue based on the enhanced permeability and retention effect, which may also bind to targets on the tumor cell surface after extravasation from the tumor vasculature, these strategies have many limitations. In this article, we discuss the concept of tumor vasculature targeting and summarize representative examples of in vivo targeted positron emission tomography imaging of various functionalized nanomaterials with different morphology, size and surface chemistry. The concept of targeting tumor vasculature instead of (or in addition to) tumor cells will continue to inspire the design of more advanced nanosystems for efficacious and personalized treatment of cancer in the future.
    Small 03/2014; · 7.82 Impact Factor
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    ABSTRACT: Molecular imaging involves the non-invasive investigation of biological processes in vivo at the cellular and molecular level, which can play diverse roles in better understanding and treatment of various diseases. Recently, single domain antigen-binding fragments known as 'nanobodies' were bioengineered and tested for molecular imaging applications. Small molecular size (~15 kDa) and suitable configuration of the complementarity determining regions (CDRs) of nanobodies offer many desirable features suitable for imaging applications, such as rapid targeting and fast blood clearance, high solubility, high stability, easy cloning, modular nature, and the capability of binding to cavities and difficult-to-access antigens. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. This review summarizes the recent developments in the use of nanobody-based probes for molecular imaging applications. The preclinical data reported to date are quite promising, and it is expected that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of various diseases.
    Theranostics 01/2014; 4(4):386-398. · 7.81 Impact Factor
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    ABSTRACT: Hollow mesoporous silica nanoparticle (HMSN) has recently gained increasing interests due to their tremendous potential as an attractive nano-platform for cancer imaging and therapy. However, possibly due to the lack of efficient in vivo targeting strategy and well-developed surface engineering techniques, engineering of HMSN for in vivo active tumor targeting, quantitative tumor uptake assessment, multimodality imaging, biodistribution and enhanced drug delivery have not been achieved to date. Here, we report the in vivo tumor targeted positron emission tomography (PET)/near-infrared fluorescence (NIRF) dual-modality imaging and enhanced drug delivery of HMSN using a generally applicable surface engineering technique. Systematic in vitro and in vivo studies have been performed to investigate the stability, tumor targeting efficacy and specificity, biodistribution and drug delivery capability of well-functionalized HMSN nano-conjugates. The highest uptake of TRC105 (which binds to CD105 on tumor neovasculature) conjugated HMSN in the 4T1 murine breast cancer model was ~10%ID/g, 3 times higher than that of the non-targeted group, making surface engineered HMSN a highly attractive drug delivery nano-platform for future cancer theranostics.
    Scientific reports. 01/2014; 4:5080.
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    ABSTRACT: Over the last several decades, development of various imaging techniques such as computed tomography, magnetic resonance imaging, and positron emission tomography greatly facilitated the early detection of cancer. Another important aspect that is closely related to the survival of cancer patients is complete tumor removal during surgical resection. The major obstacle in achieving this goal is to distinguish between tumor tissue and normal tissue during surgery. Currently, tumor margins are typically assessed by visual assessment and palpation of the tumor intraoperatively. However, the possibility of microinvasion to the surrounding tissues makes it difficult to determine an adequate tumor-free excision margin, often forcing the surgeons to perform wide excisions including the healthy tissue that may contain vital structures. It would be ideal to remove the tumor completely, with minimal safety margins, if surgeons could see precise tumor margins during the operation. Molecular imaging with optical techniques can visualize the tumors via fluorophore conjugated probes targeting tumor markers such as proteins and enzymes that are upregulated during malignant transformation. Intraoperative use of this technique may facilitate complete excision of the tumor and tumor micromasses located beyond the visual capacity of the naked eye, ultimately improving the clinical outcome and survival rates of cancer patients.
    Current pharmaceutical biotechnology 12/2013; · 3.40 Impact Factor
  • Sixiang Shi, Feng Chen, Weibo Cai
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    ABSTRACT: Hollow mesoporous silica nanoparticles (HMSNs), with a large cavity inside each original mesoporous silica nanoparticle, have recently gained increasing interest owing to their tremendous potential for cancer imaging and therapy. The last several years have witnessed a rapid development in the engineering of functionalized HMSNs (i.e., f-HMSNs), with various types of inorganic functional nanocrystals integrated into the system for imaging and therapeutic applications. In this article, we summarize the recent progress in the design and biological applications of f-HMSNs, with a special emphasis on molecular imaging. Commonly used synthetic strategies for the generation of high quality HMSNs will be discussed in detail, followed by a systematic review of engineered f-HMSNs for optical, PET, MRI and ultrasound imaging in preclinical studies. Finally, we discuss the challenges and future research directions regarding the use of f-HMSNs for cancer imaging and therapy.
    Nanomedicine 12/2013; 8(12):2027-39. · 5.26 Impact Factor
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    ABSTRACT: Functionalized nano-graphene- and graphene-based nanocomposites have gained tremendous attention in the area of biomedicine in recent years owing to their biocompatibility, the ease with which they can be functionalized and their properties such as thermal and electrical conductivity. Potential applications for functionalized nanoparticles range from drug delivery and multimodal imaging to exploitation of the electrical properties of graphene toward the preparation of biosensing devices. This protocol covers the preparation, functionalization and bioconjugation of various graphene derivatives and nanocomposites. Starting from graphite, the preparations of graphene oxide (GO), reduced GO (RGO) and magnetic GO-based nanocomposite, as well as how to functionalize them with biocompatible polymers such as polyethylene glycol (PEG), are described in detail. We also provide procedures for (125)I radiolabeling of PEGylated GO and the preparation of GO-based gene carriers; other bioconjugation approaches including drug loading, antibody conjugation and fluorescent labeling are similar to those described previously and used for bioconjugation of PEGylated carbon nanotubes. We hope this article will help researchers in this field to fabricate graphene-based bioconjugates with high reproducibility for various applications in biomedicine. The sample preparation procedures take various times ranging from 1 to 2 d.
    Nature Protocol 12/2013; 8(12):2392-403. · 8.36 Impact Factor

Publication Stats

5k Citations
716.48 Total Impact Points


  • 2008–2014
    • University of Wisconsin–Madison
      • • Department of Radiology
      • • Department of Medical Physics
      • • School of Medicine and Public Health
      Madison, Wisconsin, United States
  • 2011
    • National Institutes of Health
      Maryland, United States
    • University of Wisconsin - Milwaukee
      • Department of Mechanical Engineering
      Milwaukee, WI, United States
  • 2006–2009
    • Stanford Medicine
      • Department of Radiology
      Stanford, California, United States
  • 2005–2008
    • Stanford University
      • • Department of Medicine
      • • Department of Neurosurgery
      • • Department of Radiology
      Stanford, CA, United States