ImmunoPET and Near-Infrared Fluorescence Imaging of Pancreatic Cancer with a Dual-Labeled Bispecific Antibody Fragment.

Abstract:

:Dual-targeted imaging agents have shown improved targeting efficiencies in comparison to single-targeted entities. The purpose of this study was to quantitatively assess the tumor accumulation of a dual-labeled heterobifunctional imaging agent, targeting two overexpressed biomarkers in pancreatic cancer, using positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging modalities. A bispecific immunoconjugate (heterodimer) of CD105 and tissue factor (TF) Fab' antibody fragments was developed using click chemistry. The heterodimer was dual-labeled with a radionuclide (64Cu) and fluorescent dye. PET/NIRF imaging and biodistribution studies were performed in four-to-five week old nude athymic mice bearing BxPC-3 (CD105/TF+/+) or PANC-1 (CD105/TF-/-) tumor xenografts. A blocking study was conducted to investigate the specificity of the tracer. Ex vivo tissue staining was performed to compare TF/CD105 expression in tissues with PET tracer uptake to validate in vivo results. PET imaging of 64Cu-NOTA-heterodimer-ZW800 in BxPC-3 tumor xenografts revealed enhanced tumor uptake (21.0 ± 3.4%ID/g; n = 4) compared to the homodimer of TRC-105 (9.6 ± 2.0%ID/g; n = 4; p < 0.01) and ALT-836 (7.6 ± 3.7%ID/g; n = 4; p < 0.01) at 24 h postinjection. Blocking studies revealed that tracer uptake in BxPC-3 tumors could be decreased by 4-fold with TF blocking and 2-fold with CD105 blocking. In the negative model (PANC-1), heterodimer uptake was significantly lower than that found in the BxPC-3 model (3.5 ± 1.1%ID/g; n = 4; p < 0.01). The specificity was confirmed by the successful blocking of CD105 or TF, which demonstrated that the dual targeting with 64Cu-NOTA-heterodimer-ZW800 provided an improvement in overall tumor accumulation. Also, fluorescence imaging validated the PET imaging, allowing for clear delineation of the xenograft tumors. Dual-labeled heterodimeric imaging agents, like 64Cu-NOTA-heterodimer-ZW800, may increase the overall tumor accumulation in comparison to single-targeted homodimers, leading to improved imaging of cancer and other related diseases.

journal_name

Mol Pharm

journal_title

Molecular pharmaceutics

authors

Luo H,England CG,Goel S,Graves SA,Ai F,Liu B,Theuer CP,Wong HC,Nickles RJ,Cai W

doi

10.1021/acs.molpharmaceut.6b01123

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

1646-1655

issue

5

eissn

1543-8384

issn

1543-8392

journal_volume

14

pub_type

杂志文章
  • Chitosan-g-TPGS nanoparticles for anticancer drug delivery and overcoming multidrug resistance.

    abstract::To overcome the P-glycoprotein (P-gp)-induced multidrug resistance (MDR) of cancer cells, a novel copolymer, chitosan-graft-D-α-tocopheryl polyethylene glycol 1000 (TPGS) (CT) was synthesized for doxorubicin (DOX) delivery by the P-gp inhibiting virtue of TPGS. DOX-loaded CT nanoparticles (NPs) were fabricated by a mo...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400514t

    authors: Guo Y,Chu M,Tan S,Zhao S,Liu H,Otieno BO,Yang X,Xu C,Zhang Z

    更新日期:2014-01-06 00:00:00

  • MRI-visible micellar nanomedicine for targeted drug delivery to lung cancer cells.

    abstract::Polymeric micelles are emerging as a highly integrated nanoplatform for cancer targeting, drug delivery and tumor imaging applications. In this study, we describe a multifunctional micelle (MFM) system that is encoded with a lung cancer-targeting peptide (LCP), and encapsulated with superparamagnetic iron oxide (SPIO)...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp9001393

    authors: Guthi JS,Yang SG,Huang G,Li S,Khemtong C,Kessinger CW,Peyton M,Minna JD,Brown KC,Gao J

    更新日期:2010-02-01 00:00:00

  • Role of electrostatic potential in the in silico prediction of molecular bioactivation and mutagenesis.

    abstract::Electrostatic potential (ESP) is a useful physicochemical property of a molecule that provides insights into inter- and intramolecular associations, as well as prediction of likely sites of electrophilic and nucleophilic metabolic attack. Knowledge of sites of metabolic attack is of paramount importance in DMPK resear...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp3004385

    authors: Ford KA

    更新日期:2013-04-01 00:00:00

  • Saliva versus plasma pharmacokinetics: theory and application of a salivary excretion classification system.

    abstract::The aims of this work were to study pharmacokinetics of randomly selected drugs in plasma and saliva samples in healthy human volunteers, and to introduce a Salivary Excretion Classification System. Saliva and plasma samples were collected for 3-5 half-life values of sitagliptin, cinacalcet, metformin, montelukast, to...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300250r

    authors: Idkaidek N,Arafat T

    更新日期:2012-08-06 00:00:00

  • The Influence of High Drug Loading in Xanthan Tablets and Media with Different Physiological pH and Ionic Strength on Swelling and Release.

    abstract::The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging, and two release methods were studied. The T1 and T2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00955

    authors: Mikac U,Sepe A,Baumgartner S,Kristl J

    更新日期:2016-03-07 00:00:00

  • Optimization of the Conditions for Plasmid DNA Delivery and Transfection with Self-Assembled Hyaluronic Acid-Based Nanoparticles.

    abstract::Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA-PEG...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.8b00904

    authors: Aldawsari HM,Dhaliwal HK,Aljaeid BM,Alhakamy NA,Banjar ZM,Amiji MM

    更新日期:2019-01-07 00:00:00

  • Microparticles-in-Thermoresponsive/Bioadhesive Hydrogels as a Novel Integrated Platform for Effective Intra-articular Delivery of Triamcinolone Acetonide.

    abstract::Intra-articular (IA) injection of thermoresponsive hydrogels coupled with microparticles (MPs) possess the benefit of sustaining the anti-inflammatory drug effect within the joint cavity for rheumatoid arthritis treatment. Star-shaped thermoresponsive poly(polyethylene glycol) methacrylate [Poly(PEGMA)] copolymers wer...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.0c00126

    authors: Abou-ElNour M,Soliman ME,Skouras A,Casettari L,Geneidi AS,Ishak RAH

    更新日期:2020-06-01 00:00:00

  • Charge Shielding Prevents Aggregation of Supercharged GFP Variants at High Protein Concentration.

    abstract::Understanding protein stability is central to combatting protein aggregation diseases and developing new protein therapeutics. At the high concentrations often present in biological systems, purified proteins can exhibit undesirable high solution viscosities and poor solubilities mediated by short-range electrostatic ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00322

    authors: Laber JR,Dear BJ,Martins ML,Jackson DE,DiVenere A,Gollihar JD,Ellington AD,Truskett TM,Johnston KP,Maynard JA

    更新日期:2017-10-02 00:00:00

  • Partial biodistribution and pharmacokinetics of isoniazid and rifabutin following pulmonary delivery of inhalable microparticles to rhesus macaques.

    abstract::Dry powder inhalations (DPI) of microparticles containing isoniazid (INH) and rifabutin (RFB) are under preclinical development for use in pulmonary tuberculosis. Microparticles containing 0.25, 2.5, or 25 mg of each drug were administered daily for 90 days to rhesus macaques (n = 4/group). Single inhalations or intra...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300043f

    authors: Kumar Verma R,Mukker JK,Singh RS,Kumar K,Verma PR,Misra A

    更新日期:2012-04-02 00:00:00

  • Reversible self-assembly: a key feature for a new class of autodelivering therapeutic peptides.

    abstract::Effective delivery is a critical issue in the use of conventional free drugs. Studies on the structure-function relationship of a therapeutic antibody-derived candidacidal decapeptide (killer peptide, KP) revealed its ability to spontaneously and reversibly self-assemble in an organized network of fibril-like structur...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp900024z

    authors: Pertinhez TA,Conti S,Ferrari E,Magliani W,Spisni A,Polonelli L

    更新日期:2009-05-01 00:00:00

  • Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug recrystallization from a supersaturated solution assessed using nuclear magnetic resonance measurements.

    abstract::We examined the inhibitory effect of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) on drug recrystallization from a supersaturated solution using carbamazepine (CBZ) and phenytoin (PHT) as model drugs. HPMC-AS HF grade (HF) inhibited the recrystallization of CBZ more strongly than that by HPMC-AS LF grade ...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400278j

    authors: Ueda K,Higashi K,Yamamoto K,Moribe K

    更新日期:2013-10-07 00:00:00

  • Targeting the EphB4 receptor for cancer diagnosis and therapy monitoring.

    abstract::Accumulating evidence suggests that EphB4 plays key roles in cancer progression in numerous cancer types. In fact, therapies focusing on EphB4 have become potentially important components of various cancer treatment strategies. However, tumor sensitivity to EphB4 suppression may not be uniform for different cancers. I...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300461b

    authors: Li D,Liu S,Liu R,Park R,Hughes L,Krasnoperov V,Gill PS,Li Z,Shan H,Conti PS

    更新日期:2013-01-07 00:00:00

  • Real time measurement of PEG shedding from lipid nanoparticles in serum via NMR spectroscopy.

    abstract::Small interfering RNA (siRNA) is a novel therapeutic modality that benefits from nanoparticle mediated delivery. The most clinically advanced siRNA-containing nanoparticles are polymer-coated supramolecular assemblies of siRNA and lipids (lipid nanoparticles or LNPs), which protect the siRNA from nucleases, modulate p...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp500400k

    authors: Wilson SC,Baryza JL,Reynolds AJ,Bowman K,Keegan ME,Standley SM,Gardner NP,Parmar P,Agir VO,Yadav S,Zunic A,Vargeese C,Lee CC,Rajan S

    更新日期:2015-02-02 00:00:00

  • Sulfation patterns determine cellular internalization of heparin-like polysaccharides.

    abstract::Heparin is a highly sulfated polysaccharide that serves biologically relevant roles as an anticoagulant and anticancer agent. While it is well-known that modification of heparin's sulfation pattern can drastically influence its ability to bind growth factors and other extracellular molecules, very little is known abou...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300679a

    authors: Raman K,Mencio C,Desai UR,Kuberan B

    更新日期:2013-04-01 00:00:00

  • Using the Absorption Cocktail Approach to Assess Differential Absorption Kinetics of Cannabidiol Administered in Lipid-Based Vehicles in Rats.

    abstract::Lipid-based drug delivery systems have been vastly investigated as a pharmaceutical method to enhance oral absorption of lipophilic drugs. However, these vehicles not only affect drug bioavailability but may also have an impact on gastric emptying, drug disposition, lymphatic absorption and be affected by lipid digest...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.0c00141

    authors: Izgelov D,Regev A,Domb AJ,Hoffman A

    更新日期:2020-06-01 00:00:00

  • Polymeric nanocarriers for magnetic targeted drug delivery: preparation, characterization, and in vitro and in vivo evaluation.

    abstract::In this paper the preparation of magnetic nanocarriers (MNCs), containing superparamagnetic domains, is reported, useful as potential magnetically targeted drug delivery systems. The preparation of MNCs was performed by using the PHEA-IB-p(BMA) graft copolymer as coating material through the homogenization-solvent eva...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300718b

    authors: Licciardi M,Scialabba C,Fiorica C,Cavallaro G,Cassata G,Giammona G

    更新日期:2013-12-02 00:00:00

  • Click Biotinylation of PLGA Template for Biotin Receptor Oriented Delivery of Doxorubicin Hydrochloride in 4T1 Cell-Induced Breast Cancer.

    abstract::PLGA was functionalized with PEG and biotin using click chemistry to generate a biotin receptor targeted copolymer (biotinylated-PEG-PLGA) which in turn was used to fabricate ultrafine nanoparticles (BPNP) of doxorubicin hydrochloride (DOX) for effective delivery in 4T1 cell induced breast cancer. However, adequate en...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00310

    authors: Singh Y,Durga Rao Viswanadham KK,Kumar Jajoriya A,Meher JG,Raval K,Jaiswal S,Dewangan J,Bora HK,Rath SK,Lal J,Mishra DP,Chourasia MK

    更新日期:2017-08-07 00:00:00

  • Prediction of Small Molecule-MicroRNA Associations by Sparse Learning and Heterogeneous Graph Inference.

    abstract::As microRNAs (miRNAs) have been reported to be a type of novel high-value small molecule (SM) drug targets for disease treatments, many researchers are engaged in the field of exploring new SM-miRNA associations. Nevertheless, because of the high cost, adopting traditional biological experiments constrains the efficie...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.9b00384

    authors: Yin J,Chen X,Wang CC,Zhao Y,Sun YZ

    更新日期:2019-07-01 00:00:00

  • Modulation of Nanostructure-Based Lipopolysaccharide Active Immunotherapy in Cancer: Size and Composition Determine Short- and Long-Term Tolerability.

    abstract::Despite holding promise for cancer immunotherapy, the strong pro-inflammatory properties of lipopolysaccharide (LPS) also account for severe localized and systemic side effects, restricting its administrable dosage and the possibility of chronic dosing. Herein, we exploited the surface-active properties of LPS molecul...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.9b00631

    authors: Shetab Boushehri MA,Yazeji T,Stein V,Lamprecht A

    更新日期:2019-11-04 00:00:00

  • N-Deoxycholic acid-N,O-hydroxyethyl Chitosan with a Sulfhydryl Modification To Enhance the Oral Absorptive Efficiency of Paclitaxel.

    abstract::Currently, the most prominent barrier to the success of orally delivered paclitaxel (PTX) is the extremely limited bioavailability of delivered therapeutic. In light of this issue, an amphiphilic sulfhydrylated N-deoxycholic acid-N,O-hydroxyethyl chitosan (TGA-DHC) was synthesized to improve the oral bioavailability o...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.7b00662

    authors: Yu Y,Huo M,Fu Y,Xu W,Cai H,Yao L,Chen Q,Mu Y,Zhou J,Yin T

    更新日期:2017-12-04 00:00:00

  • Potentiating the Anticancer Properties of Bisphosphonates by Nanocomplexation with the Cationic Amphipathic Peptide, RALA.

    abstract::Bisphosphonates (BPs) are a class of bone resorptive drug with a high affinity for the hydroxyapatite structure of bone matrices that are used for the treatment of osteoporosis. However, clinical application is limited by a common toxicity, BP-related osteonecrosis of the jaw. There is emerging evidence that BPs posse...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.5b00670

    authors: Massey AS,Pentlavalli S,Cunningham R,McCrudden CM,McErlean EM,Redpath P,Ali AA,Annett S,McBride JW,McCaffrey J,Robson T,Migaud ME,McCarthy HO

    更新日期:2016-04-04 00:00:00

  • Targeted transferrin-modified polymeric micelles: enhanced efficacy in vitro and in vivo in ovarian carcinoma.

    abstract::In this study, transferrin (Tf)-modified poly(ethylene glycol)-phosphatidylethanolamine (mPEG-PE) micelles loaded with the poorly water-soluble drug, R547 (a potent and selective ATP-competitive cyclin-dependent kinase (CDK) inhibitor), were prepared and evaluated for their targeting efficiency and cytotoxicity in vit...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp300633f

    authors: Sawant RR,Jhaveri AM,Koshkaryev A,Zhu L,Qureshi F,Torchilin VP

    更新日期:2014-02-03 00:00:00

  • Phase separation in coamorphous systems: in silico prediction and the experimental challenge of detection.

    abstract::Combinatorial chemistry has enabled the production of very potent drugs that might otherwise suffer from poor solubility and low oral bioavailability. One approach to increase solubility is to make the drug amorphous, which leads to problems associated with drug stability. To improve stability, one option is to molecu...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp400712m

    authors: Pajula K,Wittoek L,Lehto VP,Ketolainen J,Korhonen O

    更新日期:2014-07-07 00:00:00

  • Effect of variations in the amounts of P-glycoprotein (ABCB1), BCRP (ABCG2) and CYP3A4 along the human small intestine on PBPK models for predicting intestinal first pass.

    abstract::It is difficult to predict the first-pass effect in the human intestine due to a lack of scaling factors for correlating in vitro and in vivo data. We have quantified cytochrome P450/3A4 (CYP3A4) and two ABC transporters, P-glycoprotein (P-gp, ABCB1) and the breast cancer resistant protein BCRP (ABCG2), throughout the...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp100015x

    authors: Bruyère A,Declèves X,Bouzom F,Ball K,Marques C,Treton X,Pocard M,Valleur P,Bouhnik Y,Panis Y,Scherrmann JM,Mouly S

    更新日期:2010-10-04 00:00:00

  • Biophysical Study on the Interaction between Eperisone Hydrochloride and Human Serum Albumin Using Spectroscopic, Calorimetric, and Molecular Docking Analyses.

    abstract::Eperisone hydrochloride (EH) is widely used as a muscle relaxant for patients with muscular contracture, low back pain, or spasticity. Human serum albumin (HSA) is a highly soluble negatively charged, endogenous and abundant plasma protein ascribed with the ligand binding and transport properties. The current study wa...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.6b01124

    authors: Rabbani G,Baig MH,Lee EJ,Cho WK,Ma JY,Choi I

    更新日期:2017-05-01 00:00:00

  • Oral suspensions of morphine hydrochloride for controlled release: rheological properties and drug release.

    abstract::Recent developments in pharmaceutical technology have facilitated the design and production of modified release formulas for drugs whose physical, chemical or biological properties impede release and thus might compromise their efficacy or safety. One such drug is morphine, whose short half-life requires repeated dose...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp200019q

    authors: Morales ME,López G,Gallardo V,Ruiz MA

    更新日期:2011-04-04 00:00:00

  • Minor N-Glycan Mapping of Monoclonal Antibody Therapeutics Using Middle-Down NMR Spectroscopy.

    abstract::The N-glycosylation pattern of Asn-297 may have impacts on monoclonal antibody (mAb) drug plasma clearance, antibody-dependent cell mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC). Notably, the changes in the relative abundance of certain minor glycans, like the afucosylation, high-mannose, o...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/acs.molpharmaceut.0c01083

    authors: Zhuo Y,Keire DA,Chen K

    更新日期:2021-01-04 00:00:00

  • Activation of the inflammasome and enhanced migration of microparticle-stimulated dendritic cells to the draining lymph node.

    abstract::Porous silicon microparticles presenting pathogen-associated molecular patterns mimic pathogens, enhancing internalization of the microparticles and activation of antigen presenting dendritic cells. We demonstrate abundant uptake of microparticles bound by the TLR-4 ligands LPS and MPL by murine bone marrow-derived de...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp3001292

    authors: Meraz IM,Melendez B,Gu J,Wong ST,Liu X,Andersson HA,Serda RE

    更新日期:2012-07-02 00:00:00

  • Bacillus-shape design of polymer based drug delivery systems with janus-faced function for synergistic targeted drug delivery and more effective cancer therapy.

    abstract::The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by t...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp500464b

    authors: Cui F,Lin J,Li Y,Li Y,Wu H,Yu F,Jia M,Yang X,Wu S,Xie L,Ye S,Luo F,Hou Z

    更新日期:2015-04-06 00:00:00

  • Intrinsic dynamics of DNA-polymer complexes: a mechanism for DNA release.

    abstract::The transfer of genetic material into cells using nonviral vectors offers unique potential for therapeutics; however, the efficacy of delivery depends upon a poorly understood, multistep pathway, limiting the prospects for successful gene delivery. Mechanistic insight into DNA association and release has been hampered...

    journal_title:Molecular pharmaceutics

    pub_type: 杂志文章

    doi:10.1021/mp3002864

    authors: Prevette LE,Nikolova EN,Al-Hashimi HM,Banaszak Holl MM

    更新日期:2012-09-04 00:00:00