Abstract:
:Tumor hypoxia plays a major role in radio- and chemotherapy resistance in solid tumors. Carbonic Anhydrase IX (CAIX) is an endogenous hypoxia-related protein, which is associated with poor patient outcome. The quantitative assessment of CAIX expression of tumors may steer cancer treatment by predicting therapy response or patient selection for antihypoxia or CAIX-targeted treatment. Recently, the single-photon emission computerized tomography (SPECT) tracer [111In]In-DTPA-girentuximab-F(ab')2 was developed and validated for targeting CAIX. The aim of this study was to optimize quantitative microSPECT/CT of CAIX expression in vivo in head and neck tumor models. Athymic mice with subcutaneous SCCNij153 and SCCNij202 head and neck squamous cell carcinoma xenografts were injected with [111In]In-DTPA-girentuximab-F(ab')2. First, the protein dose, timing, and image acquisition settings were optimized. Tracer uptake was determined by quantitative SPECT, ex vivo radioactivity counting, and by autoradiography of tumor sections. The same tumor sections were immunohistochemically stained for CAIX expression and hypoxia. Highest tumor-normal-tissue contrast was obtained at 24 h after injection of the tracer. A protein dose of 10 μg resulted in the highest tumor-to-muscle ratio at 24 h p.i. Ex vivo biodistribution studies showed a tumor uptake of 3.0 ± 0.6%ID/g and a tumor-to-muscle ratio of 8.7 ± 1.4 (SCCNij153). Quantitative analysis of the SPECT images enabled us to distinguish CAIX antigen blocked from nonblocked tumors, fractions positive for CAIX expression: 0.22 ± 0.02 versus 0.08 ± 0.01 ( p < 0.01). Immunohistochemical, autoradiographic, and microSPECT/CT analyses showed a distinct intratumoral spatial correlation between localization of the radiotracer and CAIX expression. Here, we demonstrate that [111In]In-DTPA-girentuximab-F(ab')2 specifically targets CAIX-expressing cells in head and neck cancer xenografts. SPECT imaging with indium-labeled girentuximab-F(ab')2 allows quantitative assessment of the fraction of CAIX positive tissue in head and neck cancer xenografts. These results indicate that [111In]In-DTPA-girentuximab-F(ab')2 is a promising tracer to image hypoxia-related CAIX expression.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Huizing FJ,Hoeben BAW,Franssen GM,Boerman OC,Heskamp S,Bussink Jdoi
10.1021/acs.molpharmaceut.8b00950subject
Has Abstractpub_date
2019-02-04 00:00:00pages
701-708issue
2eissn
1543-8384issn
1543-8392journal_volume
16pub_type
杂志文章abstract::Herein, we elucidated the mechanisms and key factors for the tumor-targeting ability of nanoparticles that presented high targeting efficiency for liver tumor. We used several different nanoparticles with sizes of 200-300 nm, including liposome nanoparticles (LNPs), polystyrene nanoparticles (PNPs) and glycol chitosan...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00507
更新日期:2016-11-07 00:00:00
abstract::The success of targeted cancer therapy largely relies upon the selection of target and the development of efficient therapeutic agents that specifically bind to the target. In the current study, we chose a cannabinoid CB2 receptor (CB2R) as a new target and used a CB2R-targeted photosensitizer, IR700DX-mbc94, for phot...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp5001923
更新日期:2014-06-02 00:00:00
abstract::Nucleic acid biopharmaceuticals are being investigated as potential therapeutics. They need to be incorporated into a biocompatible carrier so as to overcome several biological barriers. Rational development of suitable nanocarriers requires high-quality characterization techniques. While size, concentration, and stab...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00999
更新日期:2018-03-05 00:00:00
abstract::Constitutive activation of signal transducer and activator of transcription 3 (STAT3) in tumor cells and tumor associated dendritic cells (DCs) plays a major role in the progression of cancer. JSI-124 (cucurbitacin I) is a potent inhibitor of STAT3; however, its poor solubility and nonspecificity limit its effectivene...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b01119
更新日期:2017-08-07 00:00:00
abstract::The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid o...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500242q
更新日期:2014-10-06 00:00:00
abstract::This study aims to investigate the crystallization behavior and molecular dynamics of amorphous griseofulvin (GSF) in the presence of low-concentration poly(ethylene oxide) (PEO). We observe that the addition of 3% w/w PEO remarkably increases the crystal growth rate of GSF by two orders of magnitude in both the super...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00097
更新日期:2017-07-03 00:00:00
abstract::Abnormal extracellular deposition of β-amyloid (Aβ) is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Preventing Aβ-induced neurotoxicity has become a potential therapeutic approach to improve the onset and progression of AD. Here we report the synthesis of 1,1'-(biphenyl-4,4'-diyl)-bis(3-...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400395g
更新日期:2014-02-03 00:00:00
abstract::Our previous studies have shown that multidrug resistance protein 2 (MRP2) is overexpressed in tamoxifen-resistant MCF-7 breast cancer cells (TAMR-MCF-7 cells) and forkhead box-containing protein, O subfamily1 (FoxO1), functions as a key regulator of multidrug resistance 1 (MDR1) gene transcription. This study aimed t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400287p
更新日期:2013-07-01 00:00:00
abstract::Metastasis is the primary cause resulting in the high mortality of breast cancer. The inherent antimetastasis bioactivity of Pluronic copolymers with a wide range of hydrophilic-lipophilic balance (HLB) including Pluronic L61, P85, P123, F127, F68, and F108 was first explored on metastatic 4T1 breast cancer cells. The...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00319
更新日期:2015-09-08 00:00:00
abstract::The adenovirus (Ad) is widely used as a vaccine because of its ability to induce a cellular and humoral immune response. In addition, human clinical trials have validated the safety and efficacy of Ad as a vaccine vector. The traditional approach for employing the adenovirus as vaccine is to configure the antigen gene...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/acs.molpharmaceut.8b00591
更新日期:2018-12-03 00:00:00
abstract::Integrin αvβ3 is a cell adhesion molecule involved in the progression and invasion of glioblastoma, making it an attractive target for the diagnosis of glioblastoma. Although some integrin αvβ3 specific ligands, such as RGD and its mimetic peptides (Cilengitide), have been devoted in detecting glioblastoma, their clin...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00602
更新日期:2019-09-03 00:00:00
abstract::Recently, increased interest in drug transporters and research in this area has revealed that drug transporters play an important role in modulating drug absorption, distribution, and elimination. Acting alone or in concert with drug metabolizing enzymes they can affect the pharmacokinetics and pharmacodynamics of a d...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp050095h
更新日期:2006-01-01 00:00:00
abstract::Photodynamic therapy, a procedure that uses a photosensitizer to enable light therapy selectively at diseased sites, remains underutilized in oncological clinic. To further improve its cancer selectivity, we developed a polymeric nanosystem by conjugating a photosensitizer IRDye 700DX (IR700) and cancer targeting RGD ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00088
更新日期:2018-07-02 00:00:00
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
更新日期:2021-01-04 00:00:00
abstract::The toxicity of Amphotericin B (AmB) is contributed by the small, water-soluble aggregates of the drug. Hence, AmB lipid polymer hybrid nanoparticles (LIPOMER), comprising stearate lipids with a hydrophilic polymer Gantrez (GZ), and solid lipid nanoparticles (SLN), comprising only stearates, were prepared with the obj...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00313
更新日期:2020-06-01 00:00:00
abstract::Delivery of antigenic protein to the cytosol of antigen-presenting cells (APCs), such as macrophages (MPhi) and dendritic cells (DCs), is required for an efficient CD8 T-cell-mediated immune response. We have previously shown that co-encapsulation of antigenic protein inside pH-sensitive liposomes with listeriolysin O...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp049896v
更新日期:2005-01-01 00:00:00
abstract::Some specific types of tumor cells and tumor endothelial cells represented CD13 proteins and act as receptors for Asn-Gly-Arg (NGR) motifs containing peptide. These CD13 receptors can be specifically recognized and bind through the specific sequence of cyclic NGR (cNGR) peptide and presented more affinity and specific...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400404p
更新日期:2014-03-03 00:00:00
abstract::Heart transplantation (HT) is an effective treatment for end-stage heart disease. However, acute rejection (AR) is still the main cause of death within one year after HT. AR is an acute immune response mediated by T lymphocytes, mainly CD4+ T lymphocytes. This study innovatively develops a radiolabeled probe 99mTc-HYN...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c01155
更新日期:2021-01-28 00:00:00
abstract::In our previous studies, ethylene glycol-linked amino acid diester prodrugs of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug, designed to target peptide transporter 1 (PepT1) have been synthesized and evaluated. Unlike ethylene glycol, propylene glycol is of very low toxicity in viv...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300647m
更新日期:2013-04-01 00:00:00
abstract::Hyperbilirubinemia may arise due to inadequate clearance of bilirubin from the body. Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3. Once in the hepatocytes, it is extensively glucuronidated by UGT1A1. Eventually, the glucuronid...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4001348
更新日期:2013-08-05 00:00:00
abstract::There is a great need for delivery strategies capable of efficiently localizing drugs to the damaged myocardium that do not require direct intramyocardial injection of therapeutic molecules. In the work discussed here, we exploited the myocardium-specific upregulation of matrix metalloproteinases (MMPs) that occurs du...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500653y
更新日期:2015-04-06 00:00:00
abstract::In women with human epidermal growth factor 2 (HER2)-positive breast cancer, the improved control of systemic disease with new therapies has unmasked brain metastases that historically would have remained clinically silent. The efficacy of therapeutic agents against brain metastases is limited by their inability to pe...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b01167
更新日期:2020-02-03 00:00:00
abstract::Cytochrome c (Cyt c) is a small mitochondrial heme protein involved in the intrinsic apoptotic pathway. Once Cyt c is released into the cytosol, the caspase mediated apoptosis cascade is activated resulting in programmed cell death. Herein, we explore the covalent immobilization of Cyt c into mesoporous silica nanopar...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400400j
更新日期:2014-01-06 00:00:00
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
更新日期:2016-03-07 00:00:00
abstract::The effect of tertiary butyl alcohol (TBA) as a cosolvent on the phase behavior of mannitol in frozen and freeze-dried systems was characterized using differential scanning calorimetry (DSC) and X-ray diffractometry (XRD; laboratory and synchrotron sources). Solutions of mannitol (2 and 5% w/w) in TBA-water systems of...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00492
更新日期:2020-08-03 00:00:00
abstract::Lipid-core nanocapsules (LCNs) have been proposed as drug carriers to improve brain delivery by modulating drug pharmacokinetics (PK). However, it is not clear whether the LCNs carry the drug through the blood-brain barrier or increase free drug penetration due to changes in the barrier permeability. Quetiapine (QTP) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00875
更新日期:2016-04-04 00:00:00
abstract::The most abundant polyphenol in green tea, epigallocatechin-3-gallate (EGCg), has recently received considerable attention due to the discovery of numerous health-promoting bioactivities. Despite reports of its poor oral bioavailability, EGCg has been included in many dietary supplement formulations. Conventional pref...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4000794
更新日期:2013-08-05 00:00:00
abstract::The molecular mechanisms of autophagy in polyethylenimine (PEI)-treated cells are not well understood because of the use of nonspecific autophagy inhibitors. Here, we applied autophagy-related gene expression analysis to pinpoint the molecular mechanisms of autophagy in PEI-treated wild-type and atg5 gene knockout (at...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500111u
更新日期:2014-09-02 00:00:00
abstract::In this study, dinitrosyl iron complexes (DNICs) are shown to deliver nitric oxide (NO) into the cytosol of vascular smooth muscle cells (SMCs), which play a major role in vascular relaxation and contraction. Malfunction of SMCs can lead to hypertension, asthma, and erectile dysfunction, among other disorders. For com...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00389
更新日期:2019-07-01 00:00:00
abstract::Amphotericin B (AmB) loaded polymer lipid hybrid nanoparticles (AmB-PLNs) comprised of lecithin (anionic lipid) and gelatin (Type A, cationic below its isoelectric point 7.0-9.0) were prepared by a two-step desolvation method to improve the oral bioavailability of AmB. The optimized AmB-PLNs were found to have particl...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300320d
更新日期:2012-09-04 00:00:00