Abstract:
:The αvβ3-integrin addressing cyclic pentapeptide cyclo(RGDfK) was conjugated to NOPO, 1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid], a bifunctional chelator with exceptional gallium-68 labeling properties. NOPO-c(RGDfK) and its Ga(III) and Cu(II) complexes showed high affinity to αvβ3 integrin (IC50 = 0.94 ± 0.06, 1.02 ± 0.09, and 0.51 ± 0.06 nM, respectively). (68)Ga labeling of NOPO-c(RGDfK) in an automated GMP-compliant procedure was performed with near-quantitative radiochemical yield, using precursor amounts as low as 0.5 nmol (approximately 0.6 μg). (68)Ga-NOPO-c(RGDfK) was obtained with high purity (>99% by radio-HPLC/TLC) and, optionally, could be produced with specific activities up to 6 TBq/μmol. M21/M21L (human melanoma with high/low αvβ3 integrin expression) xenografted athymic CD-1 nude mice were used for biodistribution, in vivo stability studies, and PET imaging. (68)Ga-NOPO-c(RGDfK) showed rapid and specific uptake in M21 tumor xenografts (2.02 ± 0.34% ID/g at 60 min p.i.) and was found stable in vivo. Its high hydrophilicity is reflected by an octanol-water distribution coefficient (log D = -4.6) which is more than 1 order of magnitude lower compared to respective NOTA or DOTA analogues. As expected, (68)Ga-NOPO-c(RGDfK) thus showed fast renal clearance from nontargeted tissues. We conclude that NOPO might generally prove a useful means to improve renal clearance of corresponding radiopharmaceuticals by increasing the polarity of its bioconjugates. Favorable labeling properties render NOPO conjugates highly recommendable for reliable routine production of (68)Ga-radiopharmaceuticals in a clinical setting.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Simeček J,Notni J,Kapp TG,Kessler H,Wester HJdoi
10.1021/mp5000746subject
Has Abstractpub_date
2014-05-05 00:00:00pages
1687-95issue
5eissn
1543-8384issn
1543-8392journal_volume
11pub_type
杂志文章abstract::Ritonavir is a protease inhibitor utilized primarily as a pharmaco-enhancer with concomitantly administered antiviral drugs including other protease inhibitors. However, poor tolerance, serious side effects, and toxicities associated with drug-drug interactions are common during exposure to ritonavir. The aim of this ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00204
更新日期:2015-10-05 00:00:00
abstract::We investigated the effect of polymer composition on nifedipine (NIF) dissolution through molecular-level characterization of NIF/hypromellose (HPMC)/Eudragit S (EUD-S) ternary solid dispersions. The dissolution rates and molecular states of NIF and polymers were evaluated in NIF/HPMC/EUD-S spray-dried samples (SPDs) ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00523
更新日期:2018-09-04 00:00:00
abstract::Efficient drug delivery to the skin is essential for the treatment of major dermatologic diseases, such as eczema, psoriasis and acne. However, many compounds penetrate the skin barrier poorly and require optimized formulations to ensure their bioavailability. Here, stimulated Raman scattering (SRS) microscopy, a rece...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200122w
更新日期:2011-06-06 00:00:00
abstract::In humans, C-X-C chemokine receptor type 4 (CXCR4) is a protein that is encoded by the CXCR4 gene and binds the ligand CXCL12 (also known as SDF-1). The CXCR4-CXCL12 interaction in cancer elicits biological activities that result in tumor progression and has accordingly been the subject of significant investigation fo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00069
更新日期:2019-05-06 00:00:00
abstract::Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4002393
更新日期:2013-11-04 00:00:00
abstract::Generation 5 poly(amidoamine) (G5 PAMAM) methotrexate (MTX) conjugates employing two small molecular linkers, G5-(COG-MTX)n, G5-(MFCO-MTX)n were prepared along with the conjugates of the G5-G5 (D) dimer, D-(COG-MTX)n, D-(MFCO-MTX)n. The monomer G5-(COG-MTX)n conjugates exhibited only a weak, rapidly reversible binding...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500608s
更新日期:2014-11-03 00:00:00
abstract::Rodent models are less suitable for predicting drug-drug interactions at the level of the human intestinal mucosa, especially when nuclear receptors such as pregnane X receptor (PXR) are involved. Recently, a transgenic mouse model, expressing both human PXR and CYP3A4, was developed and shown to be a better predictor...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300512r
更新日期:2013-03-04 00:00:00
abstract::The objective of this study was to enhance oral mucosal permeation of fenretinide by coincorporation of propylene glycol (PG) and menthol in fenretinide/Eudragit RL PO mucoadhesive patches. Fenretinide is an extremely hydrophobic chemopreventive compound with poor tissue permeability. Coincorporation of 5-10 wt % PG (...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200655k
更新日期:2012-04-02 00:00:00
abstract::The formulation of drug/polymer amorphous solid dispersions (ASDs) is one of the most successful strategies for improving the oral bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Hot-melt extrusion (HME) is one method for preparing ASDs that is growing in importance in the pharmaceutical in...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00188
更新日期:2020-06-01 00:00:00
abstract::Improving the therapeutic index of anticancer agents is an enormous challenge. Targeting decreases the side effects of the therapeutic agents by delivering the drugs to the intended destination. Nanocarriers containing the nuclear localizing peptide sequences (NLS) translocate to the cell nuclei. However, the nuclear ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00014
更新日期:2017-06-05 00:00:00
abstract::Drug self-delivery systems consisting of small-molecule active drugs with nanoscale features for intracellular delivery without the need for additional polymeric carriers have drawn much attention recently. In this work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-asse...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00349
更新日期:2019-09-03 00:00:00
abstract::The Biopharmaceutical Classification System (BCS) guidance issued by the FDA allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release (IR) solid oral dosage forms only for BCS class I drugs. However, a number of drugs within BCS class III have been proposed to be eligible for biowaiv...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp100053q
更新日期:2010-08-02 00:00:00
abstract::The purpose of this study was to investigate labetalol as a potential high permeability reference standard for the application of Biopharmaceutics Classification Systems (BCS). Permeabilities of labetalol and metoprolol were investigated in animal intestinal perfusion models and Caco-2 cell monolayers. After isolating...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300410n
更新日期:2013-03-04 00:00:00
abstract::Invasion and metastasis of cancer directly related to human death have been associated with interactions among many different types of cells and three-dimensional (3D) tissue matrices. Precise mechanisms related to cancer invasion and metastasis still remain unknown due to their complexities. Development of tumor micr...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00953
更新日期:2016-07-05 00:00:00
abstract::The particular characteristics of the tumor microenvironment have the potential to strongly promote tumor growth, metastasis and angiogenesis and induce drug resistance. Therefore, the development of effective, systemic therapeutic approaches specifically based on the tumor microenvironment is highly desirable. Hypoxi...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300193f
更新日期:2012-10-01 00:00:00
abstract::Targeted delivery of anticancer drugs to brain tumors, especially glioblastoma multiforme, which is the most frequent and aggressive type, is one of the important objectives in nanomedicine. Vascular endothelial growth factor (VEGF) and its receptor type II (VEGFR2) are promising targets because they are overexpressed...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b00519
更新日期:2016-11-07 00:00:00
abstract::Amorphous solid dispersions (ASD) of a poorly soluble water-soluble VR1 antagonist (AMG 517) were explored for improving physical stability and in vivo exposure. AMG 517 was incorporated at 15 or 50 wt % into polymeric microparticles of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and hydroxypropyl methylc...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp800061r
更新日期:2008-11-01 00:00:00
abstract::Major obstacles in the development of new therapeutic anticancer drugs are the low bioavailability of hydrophilic substances and the nonspecific toxicity toward healthy tissues. As such, cell-targeting oligopeptides have emerged as attractive drug delivery vehicles for a variety of different types of cargo. The recent...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp060122j
更新日期:2007-05-01 00:00:00
abstract::DEK protein is critical to the formation of neutrophil extracellular traps (NETs) in rheumatoid arthritis (RA). Blocking DEK using the aptamer DTA via articular injection has been shown to have robust anti-inflammatory efficacy in a previous study. However, DTA is prone to nuclease degradation and renal clearance in v...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00954
更新日期:2021-01-04 00:00:00
abstract::Delta-like ligand 4 (Dll4) expressed in tumor cells plays a key role to promote tumor growth of numerous cancer types. Based on a novel antihuman Dll4 monoclonal antibody (61B), we developed a (64)Cu-labeled probe for positron emission tomography (PET) imaging of tumor Dll4 expression. In this study, 61B was conjugate...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.5b00105
更新日期:2015-10-05 00:00:00
abstract::Herein, we report on the role of endocytosis in the selective chemotherpeutic toxicity of rhodamine 6G (R6G) based nanomaterials, i.e., nanoGUMBOS, that are derived from a group of uniform materials based on organic salts (GUMBOS). Evaluation of cellular uptake in the presence and absence of endocytosis inhibitors sug...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00339
更新日期:2018-09-04 00:00:00
abstract::There is evidence that encapsulating glucocorticoids into nucleic acid-containing nanoparticles reduces the inflammatory toxicities of the nanoparticles. Herein, using betamethasone acetate (BA), a glucocorticoid, and a solid lipid nanoparticle formulation of siRNA, we confirmed that coencapsulating BA into the siRNA ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00629
更新日期:2019-11-04 00:00:00
abstract::Extracellular β-glucuronidase (β-GUS) in tumors has been investigated as a target enzyme for prodrug therapy. However, despite encouraging preclinical results, animal studies also indicate that the success of prodrug therapy might be limited by the insufficient prodrug-converting enzyme activity, especially in small t...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300327w
更新日期:2012-11-05 00:00:00
abstract::Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide, but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood-brain barrier (BBB) and in neurons the e...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300496x
更新日期:2013-01-07 00:00:00
abstract::The complement system plays an important role in host innate immunity, and its activation can be exploited as a potential strategy for vaccine adjuvants. Herein, a pH-responsive micellar vaccine platform (COOH-NPs) was developed using a carboxyl-modified diblock copolymer of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide)...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.9b00195
更新日期:2019-06-03 00:00:00
abstract::Achieving effective gene therapy for glioma depends on gene delivery systems. The gene delivery system should be able to cross the blood-brain barrier (BBB) and further target glioma at its early stage. Active brain tumor targeted delivery can be achieved using the "Trojan horse" technology, which involves either endo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500084s
更新日期:2014-10-06 00:00:00
abstract::An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake, and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and su...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b01141
更新日期:2017-05-01 00:00:00
abstract::Cell penetrating peptides (CPPs) have been extensively studied in polyelectrolyte complexes as a means to enhance the transfection efficiency of plasmid DNA (pDNA). Increasing the molecular weight of CPPs often enhances gene expression but poses a risk of increased cytotoxicity and immunogenicity compared to low molec...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3007117
更新日期:2013-05-06 00:00:00
abstract::Metastatic breast cancer is incurable. The goal of this study was to develop a positron emission tomography (PET)/near-infrared fluorescent (NIRF) probe for imaging CD105 expression in breast cancer experimental lung metastasis. TRC105, a chimeric anti-CD105 antibody, was dual-labeled with a NIRF dye (IRDye 800CW) and...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300277f
更新日期:2012-08-06 00:00:00
abstract::Carbonic anhydrase IX (CAIX) plays an important role in glioma cell proliferation, invasion, metastasis, and resistance to radiotherapy and chemotherapy. An effective and noninvasive PET molecular imaging agent targeting CAIX would help its diagnosis and treatment but is not currently available. Recently, a low-molecu...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b01210
更新日期:2019-04-01 00:00:00