Abstract:
:Positron emission tomography (PET) imaging using 68Ga-labeled bisphosphonates to target bone metastasis could be a valuable tool in cancer diagnosis and monitoring therapeutic treatment. A 68Ga labeled ligand, N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC) containing one bisphosphonate group (HBED-CC-BP, 1) was prepared and evaluated. The new ligand, 1, reacted rapidly to form [68Ga]Ga-1, via complexing with [68Ga]GaCl3 eluted from a commercially available 68Ge/68Ga generator (in a sodium acetate buffer at pH 4, reaching >95% labeling yield at room temperature in 5 min). The resulting [68Ga]Ga-1 showed excellent stability in vitro and in vivo. [68Ga]Ga-1 displayed high binding affinity to hydroxyapatite and good uptake in the tibia and femur bone of normal mice. Biodistribution and MicroPET imaging studies of [68Ga]Ga-1 in normal mice and rats showed excellent bone uptake and retention comparable to that of Na[18F]F. The results suggested that [68Ga]Ga-1 might be suitable as a bone imaging agent in humans and it could be useful as a convenient alternative to the current bone imaging PET agent, Na[18F]F, without the need of a near-by cyclotron. Also, an automated synthesis module was developed to produce clinical doses of [68Ga]Ga-1 in a consistent and reproducible manner. Currently, the investigation new drug application (IND) for [68Ga]Ga-HBED-CC-BP, [68Ga]Ga-1, has received FDA approval, and it is currently under clinical trial (IND #129870).
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Zha Z,Wu Z,Choi SR,Ploessl K,Smith M,Alexoff D,Zhu L,Kung HFdoi
10.1021/acs.molpharmaceut.0c00103subject
Has Abstractpub_date
2020-05-04 00:00:00pages
1674-1684issue
5eissn
1543-8384issn
1543-8392journal_volume
17pub_type
杂志文章abstract::Stably transfected MDCK/hPepT1-V5&His clonal cell lines expressing varying levels of epitope-tagged hPepT1 protein were established to quantify the relationship between transgene hPepT1 expression levels and its functional kinetics in facilitating peptide and peptide-like drug uptake and transport in vitro. The hPepT1...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp034011l
更新日期:2004-03-01 00:00:00
abstract::Solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX) is a promising method for characterizing proteins in amorphous solids. Though analysis of HDX kinetics is informative and well-established in solution, application of these methods to solid samples is complicated by possible heterogeneiti...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp2004093
更新日期:2012-04-02 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::Glutamic acid is a commonly used linker to form dimeric peptides with enhanced binding affinity than their corresponding monomeric counterparts. We have previously labeled NOTA-Bn-NCS-PEG3-E[c(RGDyK)]2 (NOTA-PRGD2) [1] with [(18)F]AlF and (68)Ga for imaging tumor angiogenesis. The p-SCN-Bn-NOTA was attached to E[c(RGD...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400706q
更新日期:2014-11-03 00:00:00
abstract::The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent on the volume of liquid in the gastrointestinal tract (GIT). However, little is known about the time course of GIT liquid volumes after drinking a glass of water (8 oz), particularly in the colon, which is a targete...
journal_title:Molecular pharmaceutics
pub_type: 临床试验,杂志文章
doi:10.1021/acs.molpharmaceut.7b00095
更新日期:2017-08-07 00:00:00
abstract::We report herein on the preparation of thermoresponsive hydrogels by taking advantage of the interaction of cyclodextrins (CDs) and a hydrophobically modified polymer. A hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC) gel formed thermoresponsive hydrogels when small amounts of α-CD were added to the s...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00291
更新日期:2017-08-07 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::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::An ability to estimate the maximum flux of a xenobiotic across skin is desirable from the perspective of both drug delivery and toxicology. While there is an abundance of mathematical models describing the estimation of drug permeability coefficients, there are relatively few that focus on the maximum flux. This artic...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300146m
更新日期:2012-07-02 00:00:00
abstract::We present a new approach for characterizing drug-polymer interactions in aqueous media, using sedimentation velocity analytical ultracentrifugation (AUC). We investigated the potential interaction of ketoconazole (KTZ), a poorly water-soluble drug, with polyacrylic acid (PAA) and a polyvinyl caprolactam-polyvinyl ace...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00849
更新日期:2021-01-04 00:00:00
abstract::In this manuscript, we have reported a novel 2D fingerprint-based artificial neural network QSAR (FANN-QSAR) method in order to effectively predict biological activities of structurally diverse chemical ligands. Three different types of fingerprints, namely, ECFP6, FP2 and MACCS, were used in FANN-QSAR algorithm devel...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp300237z
更新日期:2012-10-01 00:00:00
abstract::The purpose of this study was to examine the melanoma targeting and imaging properties of two new (99m)Tc-labeled Arg-X-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RTD-Lys-(Arg(11))CCMSH {c[Asp-Arg-Thr-Asp-DTyr]-Lys-Cys-Cys-Glu-His-DPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2} and RVD-Lys-(Arg(11))CCMSH pept...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp400248f
更新日期:2013-09-03 00:00:00
abstract::Targeting of drugs administered systemically relies on the higher affinity of ligands for specific receptors to obtain selectivity in drug response. However, achieving the same goal inside the bladder is much easier with an intelligent pharmaceutical approach that restricts drug effects by exploiting the pelvic anatom...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp060001j
更新日期:2006-07-01 00:00:00
abstract::Tumor endothelial marker 8 (TEM8) is a cell surface receptor that is highly expressed in a variety of human tumors and promotes tumor angiogenesis and cell growth. Antibodies targeting TEM8 block tumor angiogenesis in a manner distinct from the VEGF receptor pathway. Development of a TEM8 imaging agent could aid in pa...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500056d
更新日期:2014-11-03 00:00:00
abstract::Contrast-enhanced ultrasound imaging has shown promise in the field of molecular imaging. This technique relies upon the adhesion of ultrasound contrast agent (UCA) to targeted molecular markers of disease. This is accomplished by coating the surface of the contrast agent with a ligand that specifically binds to the i...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp0600541
更新日期:2006-09-01 00:00:00
abstract::Currently, the screening of new drug candidates for intestinal permeation is typically based on in vitro models which give no information regarding regional differences along the gut. When evaluation of intestinal permeability by region is undertaken, two preclinical rat models are commonly used, the Ussing chamber me...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00279
更新日期:2017-12-04 00:00:00
abstract::A wide variety of chemotherapy and radiotherapy agents are available for treating cancer, but a critical challenge is to deliver these agents locally to cancer cells and tumors while minimizing side effects from systemic delivery. Nanomedicine uses nanoparticles with diameters in the range of ∼1-100 nm to encapsulate ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章,评审
doi:10.1021/mp400419k
更新日期:2014-01-06 00:00:00
abstract::Interactions of a lyophilized peptide with water and excipients in a solid matrix were explored using photolytic labeling. A model peptide "KLQ" (Ac-QELHKLQ-NHCH3) was covalently labeled with NHS-diazirine (succinimidyl 4,4'-azipentanoate), and the labeled peptide (KLQ-SDA) was formulated and exposed to UV light in bo...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b01031
更新日期:2019-03-04 00:00:00
abstract::The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact on the plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential, and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viabil...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp4005035
更新日期:2014-02-03 00:00:00
abstract::The successful applicability of gene therapy approaches will heavily rely on the development of efficient and safe nonviral gene delivery vectors, for example, cell-penetrating peptides (CPPs). CPPs can condense oligonucleotides and plasmid DNA (pDNA) into nanoparticles, thus allowing the transfection of genetic mater...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp3003557
更新日期:2013-01-07 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::New bifunctional hexa- and octadentate analogues of the hydroxamate-containing siderophore desferrichrome (DFC) have been synthesized and evaluated as 89Zr-chelating agents for immunoPET applications. The in vitro and in vivo inertness of these new ligands, Orn3-hx (hexadentate) and Orn-4hx derivatives (octadentate), ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.7b00343
更新日期:2017-08-07 00:00:00
abstract::Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.0c00937
更新日期:2021-01-11 00:00:00
abstract::Fluid bed coating has been shown to be a suitable manufacturing technique to formulate poorly soluble drugs in glass solutions. Layering inert carriers with a drug-polymer mixture enables these beads to be immediately filled into capsules, thus avoiding additional, potentially destabilizing, downstream processing. In ...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.6b01023
更新日期:2017-04-03 00:00:00
abstract::Lipid nanoemulsions are being investigated for the parenteral administration of poorly soluble drugs. A narrow particle size distribution in these formulations is a prerequisite for meaningful research and safe administration to patients. Autoclaving a poloxamer-stabilized trimyristin nanoemulsion resulted in moderate...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00202
更新日期:2018-08-06 00:00:00
abstract::Colistin has been increasingly used for the treatment of respiratory infections caused by Gram-negative bacteria. Unfortunately parenteral administration of colistin can cause severe adverse effects. This study aimed to develop an inhaled combination dry powder formulation of colistin and rifapentine for the treatment...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500586p
更新日期:2015-08-03 00:00:00
abstract::Due to the aging of the population, the incidence of neurodegenerative diseases, such as Parkinson's and Alzheimer's, is expected to grow and, hence, the demand for adequate treatment modalities. However, the delivery of medicines into the brain for the treatment of brain-related diseases is hampered by the presence o...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp200621v
更新日期:2012-06-04 00:00:00
abstract::It is well-known that renal cell carcinomas (RCCs) are resistant to classical cytotoxic anticancer drugs. Therefore, facilitating the impact of anticancer drugs by altering the cell phenotype should be a useful strategy for circumventing this. We developed a multifunctional envelope-type nanodevice (MEND) as an in viv...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500245z
更新日期:2014-08-04 00:00:00
abstract::Active targeting of nanostructures containing chemotherapeutic agents can improve cancer treatment. Here, a three-way junction pocket DNA nanostructure was developed for efficient doxorubicin (Dox) delivery into cancer cells. The three-way junction pocket DNA nanostructure is composed of three strands of AS1411 aptame...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/acs.molpharmaceut.8b00124
更新日期:2018-05-07 00:00:00
abstract::The blood-brain barrier (BBB) prevents most drugs from reaching the site of central nervous system (CNS) diseases, intensively confining the therapeutic efficiency. Angiopep-2 (here termed (L)Angiopep), which is a 19-mer peptide derived from human Kunitz domain, can trigger transcytosis and traverse the BBB by recogni...
journal_title:Molecular pharmaceutics
pub_type: 杂志文章
doi:10.1021/mp500086e
更新日期:2014-10-06 00:00:00