scholarly journals Evaluation of Radioiodinated Fluoronicotinamide/Fluoropicolinamide-Benzamide Derivatives as Theranostic Agents for Melanoma

2020 ◽  
Vol 21 (18) ◽  
pp. 6597
Author(s):  
Chao-Cheng Chen ◽  
Yang-Yi Chen ◽  
Yi-Hsuan Lo ◽  
Ming-Hsien Lin ◽  
Chih-Hsien Chang ◽  
...  
Keyword(s):  
Absorbed Dose ◽  
Radiochemical Yield ◽  
Amelanotic Melanoma ◽  
In Vivo Studies ◽  
Log P ◽  
Theranostic Agent ◽  
Biodistribution Studies ◽  
Theranostic Agents

Malignant melanoma is the most harmful type of skin cancer and its incidence has increased in this past decade. Early diagnosis and treatment are urgently desired. In this study, we conjugated picolinamide/nicotinamide with the pharmacophore of 131I-MIP-1145 to develop 131I-iodofluoropicolinamide benzamide (131I-IFPABZA) and 131I-iodofluoronicotiamide benzamide (131I-IFNABZA) with acceptable radiochemical yield (40 ± 5%) and high radiochemical purity (>98%). We also presented their biological characteristics in melanoma-bearing mouse models. 131I-IFPABZA (Log P = 2.01) was more lipophilic than 131I-IFNABZA (Log P = 1.49). B16F10-bearing mice injected with 131I-IFNABZA exhibited higher tumor-to-muscle ratio (T/M) than those administered with 131I-IFPABZA in planar γ-imaging and biodistribution studies. However, the imaging of 131I-IFNABZA- and 131I-IFPABZA-injected mice only showed marginal tumor uptake in A375 amelanotic melanoma-bearing mice throughout the experiment period, indicating the high binding affinity of these two radiotracers to melanin. Comparing the radiation-absorbed dose of 131I-IFNABZA with the melanin-targeted agents reported in the literature, 131I-IFNABZA exerts lower doses to normal tissues on the basis of similar tumor dose. Based on the in vitro and in vivo studies, we clearly demonstrated the potential of using 131I-IFNABZA as a theranostic agent against melanoma.

68Ga-labeled HBED-CC Variant of uPAR Targeting Peptide AE105 Compared with 68Ga-NODAGA-AE105

2019 ◽  
Vol 18 (9) ◽  
pp. 1289-1294 ◽  
Author(s):  
Kusum Vats ◽  
Rohit Sharma ◽  
Haladhar D. Sarma ◽  
Drishty Satpati ◽  
Ashutosh Dash
Keyword(s):  
Solid Phase ◽  
Evaluation Studies ◽  
Radiochemical Yield ◽  
In Vivo Evaluation ◽  
Peptide Conjugates ◽  
Biodistribution Studies ◽  
Target Organs ◽  
U87mg Tumor

Aims: The urokinase Plasminogen Activator Receptors (uPAR) over-expressed on tumor cells and their invasive microenvironment are clinically significant molecular targets for cancer research. uPARexpressing cancerous lesions can be suitably identified and their progression can be monitored with radiolabeled uPAR targeted imaging probes. Hence this study aimed at preparing and evaluating two 68Ga-labeled AE105 peptide conjugates, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 as uPAR PET-probes. Method: The peptide conjugates, HBED-CC-AE105-NH2 and NODAGA-AE105-NH2 were manually synthesized by standard Fmoc solid phase strategy and subsequently radiolabeled with 68Ga eluted from a commercial 68Ge/68Ga generator. In vitro cell studies for the two radiotracers were performed with uPAR positive U87MG cells. Biodistribution studies were carried out in mouse xenografts with the subcutaneously induced U87MG tumor. Results: The two radiotracers, 68Ga-NODAGA-AE105 and 68Ga-HBED-CC-AE105 that were prepared in >95% radiochemical yield and >96% radiochemical purity, exhibited excellent in vitro stability. In vivo evaluation studies revealed higher uptake of 68Ga-HBED-CC-AE105 in U87MG tumor as compared to 68Ga-NODAGAAE105; however, increased lipophilicity of 68Ga-HBED-CC-AE105 resulted in slower clearance from blood and other non-target organs. The uPAR specificity of the two radiotracers was ascertained by significant (p<0.05) reduction in the tumor uptake with a co-injected blocking dose of unlabeled AE-105 peptide. Conclusion: Amongst the two radiotracers studied, the neutral 68Ga-NODAGA-AE105 with more hydrophilic chelator exhibited faster clearance from non-target organs. The conjugation of HBED-CC chelator (less hydrophilic) resulted in negatively charged 68Ga-HBED-CC-AE105 which was observed to have high retention in blood that decreased target to non-target ratios.

Gold Nanoparticles as Targeted Delivery Systems and Theranostic Agents in Cancer Therapy

2019 ◽  
Vol 26 (35) ◽  
pp. 6493-6513 ◽  
Author(s):  
Alexandra Mioc ◽  
Marius Mioc ◽  
Roxana Ghiulai ◽  
Mirela Voicu ◽  
Roxana Racoviceanu ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Anticancer Agents ◽  
Targeted Delivery ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
In Vivo Studies ◽  
Theranostic Agents ◽  
Targeted Delivery Systems

Cancer is still a leading cause of death worldwide, while most chemotherapies induce nonselective toxicity and severe systemic side effects. To address these problems, targeted nanoscience is an emerging field that promises to benefit cancer patients. Gold nanoparticles are nowadays in the spotlight due to their many well-established advantages. Gold nanoparticles are easily synthesizable in various shapes and sizes by a continuously developing set of means, including chemical, physical or eco-friendly biological methods. This review presents gold nanoparticles as versatile therapeutic agents playing many roles, such as targeted delivery systems (anticancer agents, nucleic acids, biological proteins, vaccines), theranostics and agents in photothermal therapy. They have also been outlined to bring great contributions in the bioimaging field such as radiotherapy, magnetic resonance angiography and photoacoustic imaging. Nevertheless, gold nanoparticles are therapeutic agents demonstrating its in vitro anti-angiogenic, anti-proliferative and pro-apoptotic effects on various cell lines, such as human cervix, human breast, human lung, human prostate and murine melanoma cancer cells. In vivo studies have pointed out data regarding the bioaccumulation and cytotoxicity of gold nanoparticles, but it has been emphasized that size, dose, surface charge, sex and especially administration routes are very important variables.

Radioiodination and biological evaluation of Cimetidine as a new highly selective radiotracer for peptic ulcer disorder detection

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Mahmoud H. Sanad ◽  
Safaa B. Challan ◽  
Fawzy A. Marzook ◽  
Sayed M. Abd-Elhaliem ◽  
Ebtisam A. Marzook
Keyword(s):  
Peptic Ulcer ◽  
Nuclear Imaging ◽  
Radiochemical Yield ◽  
Biological Evaluation ◽  
Stomach Ulcer ◽  
Control Group ◽  
Factors Affecting ◽  
Biodistribution Studies

AbstractOne of the most famous techniques for stomach ulcer imaging is the nuclear imaging technique. We aim to focus on the synthesis of 125I-cimetidine (125I-cim) as an agent for peptic ulcer imaging. Cimetidine was labeled with Iodine-125 using a different oxidizing agent (Ch-T, NBS). All factors affecting the labeling yield were optimized. The radiochemical yield of 125I-cim was 98 ± 0.22% at optimum conditions. In vitro stability, in vivo biodistribution of 125I-cimetidine was studied in three groups: control group, pretreated group, and ulcer bearing group. In vivo biodistribution studies of 125I-cim revealed high uptake in the stomach ulcer, reaching about 75.4 ± 1.2% ID/g at 15 min post-injection, than pretreated groups compared to the control. The results showed the suitability of using 125I-cimetidine for stomach ulcer imaging.

scholarly journals Iron Oxide Incorporated Conjugated Polymer Nanoparticles for Simultaneous Use in Magnetic Resonance and Fluorescent Imaging of Brain Tumors

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1258
Author(s):  
N. Arias-Ramos ◽  
L. E. Ibarra ◽  
M. Serrano-Torres ◽  
B. Yagüe ◽  
M. D. Caverzán ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Conjugated Polymer ◽  
Colloidal Stability ◽  
Fluorescent Imaging ◽  
Polymer Nanoparticles ◽  
Biodistribution Studies ◽  
Conjugated Polymer Nanoparticles ◽  
Theranostic Agents

Conjugated polymer nanoparticles (CPNs) have emerged as advanced polymeric nanoplatforms in biomedical applications by virtue of extraordinary properties including high fluorescence brightness, large absorption coefficients of one and two-photons, and excellent photostability and colloidal stability in water and physiological medium. In addition, low cytotoxicity, easy functionalization, and the ability to modify CPN photochemical properties by the incorporation of dopants, convert them into excellent theranostic agents with multifunctionality for imaging and treatment. In this work, CPNs were designed and synthesized by incorporating a metal oxide magnetic core (Fe3O4 and NiFe2O4 nanoparticles, 5 nm) into their matrix during the nanoprecipitation method. This modification allowed the in vivo monitoring of nanoparticles in animal models using magnetic resonance imaging (MRI) and intravital fluorescence, techniques widely used for intracranial tumors evaluation. The modified CPNs were assessed in vivo in glioblastoma (GBM) bearing mice, both heterotopic and orthotopic developed models. Biodistribution studies were performed with MRI acquisitions and fluorescence images up to 24 h after the i.v. nanoparticles administration. The resulting IONP-doped CPNs were biocompatible in GBM tumor cells in vitro with an excellent cell incorporation depending on nanoparticle concentration exposure. IONP-doped CPNs were detected in tumor and excretory organs of the heterotopic GBM model after i.v. and i.t. injection. However, in the orthotopic GBM model, the size of the nanoparticles is probably hindering a higher effect on intratumorally T2-weighted images (T2WI) signals and T2 values. The photodynamic therapy (PDT)—cytotoxicity of CPNs was not either affected by the IONPs incorporation into the nanoparticles.

scholarly journals Synthesis and Preclinical Evaluation of 68Ga-MALAT-1 ASO for PET Imaging of MALAT-1 expressing Tumours

2020 ◽  
Author(s):  
Zhen-Feng Liu ◽  
Jun Yang ◽  
Qianni Ye ◽  
Min Yang ◽  
Dong-hui Pan ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Malignant Tumors ◽  
Radiochemical Yield ◽  
Cell Uptake ◽  
Log P ◽  
Pharmacokinetic Studies ◽  
Specific Uptake ◽  
Pet Scans

Abstract Background: MALAT-1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) is a large long nuclear noncoding RNA (lncRNA) that is overexpressed in an array of cancers. In this study, we designed a range of positron probes for MALAT-1 to evaluate its distribution, pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumors with high MALAT-1 expression in vivo. Methods: 68Ga labelling of MALAT-1 antisense oligonucleotides (68Ga–MALAT-1 ASO) was synthesized by the conjugation of MALAT-1 NOTA-ASO and 68Ga3+. Purity was assessed by radio-HPLC. Pharmacokinetic studies and cell uptake were assessed. The biodistribution and metabolism of 68Ga–MALAT-1 ASO in normal ICR and MHCC-LM3 xenograft-bearing nude mice were studied. Results: 68Ga–MALAT-1 ASO was obtained at a radiochemical yield of 98% from a 10 min synthesis with 100 ± 50 MBq/nmol activity and > 99% purity once synthesized. The Log P was -2.53±0.19. The tracer displayed excellent stability in vitro. 68Ga–MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of 68Ga-MALAT-1 ASO in MHCC-LM3 tumour-bearing mice showed high levels of uptake (3.04 ± 0.11%ID/g). Micro-PET scans demonstrated the tumor specific uptake of 68Ga-MALAT-1 ASO in mouse models. Conclusions: We conclude that 68Ga labelling of MALAT-1 ASO is a convenient approach to label tumors overexpressing MALAT-1.

In vitro and in vivo Evaluation of the Radiochemical Compound Based on 99mTechnetium Labelled DARPin 9_29 for Molecular Visualization of Malignancies Overexpressing Her2/neu

2020 ◽  
Vol 65 (1) ◽  
pp. 37-41
Author(s):  
O. Bragina ◽  
A. Vorobyeva ◽  
V. Tolmachev ◽  
A. Orlova ◽  
V. Chernov ◽  
...  
Keyword(s):  
In Vitro Study ◽  
Radiochemical Yield ◽  
Blood Stream ◽  
The Body ◽  
Diagnostic Methods ◽  
In Vivo Studies ◽  
In Vivo Evaluation ◽  
High Accumulation

Purpose: Evaluation of a radiopharmaceutical based on 99mTc-labeled targeted molecules DARPin9_29 for radionuclide diagnostics of malignancies with Her2/neu overexpression. Material and methods: The DARPin9_29 sequence was amplified from the plasmid pET-DARP-6HIS for the DARPin9_29-His6 gene expression in E. coli cells. The eluent of 99mTcO4– (400–500 μl, 4 GBq) was added to the kit and incubated at a temperature of 100 °C for 20 minutes. After incubation, 40 μl of tricarbonyl technetium was added to 168 μg of DARPin9_29 in 100 μl of PBS (sodium phosphate buffer), followed by incubation at 40 °C for 60 minutes. The radiochemical yield and purity were determined by thin layer radiochromatography, the purification was performed using NAP-5 cleansing columns (GE Healthcare). Cell lines with different levels of Her2/neu expression were used: SKOV-3> BT474 >> DU-145 for the determination of the radiopharmaceutical specificity. Her2/neu expressing cell line SKOV-3 was used for in vitro study. The study was conducted 6 hours after the administration of the drug. Results: The radiochemical yield was 72 ± 8 %, the radiochemical purity after purification was 98.7 ± 1.0 %. The stability in PBS (phosphate buffered saline) solution after 1 hour was 99.8 ± 0.2; after 3 hours – 98.2 ± 0.1. In vitro studies showed that the accumulation of explored compound was directly proportional to the level of Her2/neu expression in cells, while blocking the receptors with an excess of unlabeled protein showed a significant reduction in binding in the group of cells. Data on biodistribution and SPECT/CT in the body of the animal BALB/c nu/nu demonstrated rapid removal of the compound from the blood stream and high accumulation in the liver, kidney and bladder 6 hours after the introduction of the radiopharmaceutical. Conclusion: The studies demonstrated high radiochemical yields and purity, as well as stability of the studied compound. The results of in vitro and in vivo analysis showed the specificity and affinity of the radiopharmaceutical to the Her2/neu receptor on the surface of tumor cells. The high accumulation of the drug in the liver and kidneys, detected in in vivo studies, is probably due to the lipophilicity of the 99mTc(CO)3-histidine tag and indicates the limitation of its further clinical use in assessing the condition of the above organs, which will require additional diagnostic methods, as well as possible modification chemical structure.

High non-specific binding of the β1-selective radioligand 2-125I-ICI-H

2003 ◽  
Vol 42 (04) ◽  
pp. 173-180 ◽  
Author(s):  
M. P. Law ◽  
K. Kopka ◽  
St. Wagner ◽  
S. Luthra ◽  
V. W. Pike ◽  
...  
Keyword(s):  
Specific Activity ◽  
Single Photon ◽  
Specific Binding ◽  
Photon Emission ◽  
Radiochemical Yield ◽  
Emission Computed Tomography ◽  
Biodistribution Studies ◽  
Positron Emission

Summary: Aim: As results of cardiac biopsies suggest, myocardial β1-adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac β2-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess β-adrenoceptors non-invasively. Among the novel racemic analogues of the established β1-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to β1-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective β1-adrenergic radioligand in cardiac imaging. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac β-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-125I-ICI-H from the silylated precursor 2-SiMe3-ICI-H was established. The specific activity was 80 GBq/µmol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high β1-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac β-adrenoceptors. The radiolabelled counterpart 2-125I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac β1-adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-125I-ICI-H is no suitable radiotracer for imaging in vivo.

Biodegradable Polymeric Nanoparticles for Tumor-Selective Tamoxifen Delivery: In Vitro and in Vivo Studies

2004 ◽  
Vol 845 ◽  
Author(s):  
Dinesh B. Shenoy ◽  
Jugminder S. Chawla ◽  
Mansoor M. Amiji
Keyword(s):  
Cellular Uptake ◽  
Polymeric Nanoparticles ◽  
Therapeutic Benefit ◽  
In Vivo Studies ◽  
Tumor Mass ◽  
Biodistribution Studies ◽  
Poly Ethylene ◽  
Surface Modified

1. ABSTRACT: This study was performed to evaluate the in-vitro and in-vivo tumor-cellular uptake and biodistribution pattern of tamoxifen when administered intravenously as a simple solution and upon encapsulation into biodegradable, surface-modified poly(ε-caprolactone) (PCL) nanoparticles. PCL (MW ∼ 15, 000) nanoparticles were prepared by the solvent displacement method and characterized for particle size/charge and surface morphology (by scanning electron microscopy). We investigated the nanoparticle-surface modification potential of the hydrophilic stabilizer (Pluronic® F-68 and F-108) employed during the preparation by electron spectroscopy for chemical analysis (ESCA). Quantitative in-vitro cellular uptake of tritiated (3H) tamoxifen in solution form and as nanoparticulate formulation was assessed in MCF-7 breast cancer cells. In-vivo biodistribution studies for the same formulations were carried out in Nu/Nu mice bearing MDA-MB-231 human breast carcinoma xenograft. Spherical nanoparticles having positive zeta potential (∼25 mV) were obtained in the size range of 200-300 nm. Pluronics (both F-68 and F-108), the triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) induced surface hydrophilization of the nanoparticles via adsorption as evident by ESCA. Nanoparticulate formulations of tamoxifen achieved higher intracellular concentrations when exposed at therapeutic concentrations to tumor cells in-vitro compared to solutions. The in-vivo biodistribution studies carried out in nude mice bearing experimental breast tumor suggested increased tumor concentrations for the drug administered as nanoparticulate formulations besides longer retention times within tumor mass. This type of delivery system is expected to provide better therapeutic benefit by dual means: preferential concentration within the tumor mass via enhanced permeation and retention pathway, and; subsequent controlled release, thus maintaining the local drug concentration for longer periods of time to achieve maximal cell-kill.

scholarly journals Tetraphenylethene-based highly emissive metallacage as a component of theranostic supramolecular nanoparticles

2016 ◽  
Vol 113 (48) ◽  
pp. 13720-13725 ◽  
Author(s):  
Guocan Yu ◽  
Timothy R. Cook ◽  
Yang Li ◽  
Xuzhou Yan ◽  
Dan Wu ◽  
...  
Keyword(s):  
Cancer Treatment ◽  
Self Assembly ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Active Components ◽  
Theranostic Agent ◽  
Supramolecular Coordination ◽  
Targeting Ability

A theranostic agent combines diagnostic reporter with therapeutic activity in a single entity, an approach that seeks to increase the efficacy of cancer treatment. Herein, we describe the synthesis of a highly emissive tetraphenylethene-based metallacage using multicomponent coordination-driven self-assembly that exhibits a coordination-triggered aggregation-induced emission (AIE) enhancement. The formation of metallacage-loaded nanoparticles (MNPs) occurs when the assembly is treated with two variants of a 1,2-distearoyl-phosphatidylethanolamine (DSPE)/polyethylene glycol (PEG) conjugate, mPEG-DSPE, and biotin-PEG-DSPE. This combination endows the resultant MNPs with excellent stability and targeting ability, specifically enabling selective delivery of the metallacages to cancer cells that overexpress biotin receptors via receptor-mediated endocytosis. Although the mechanism of activity is based on existing Pt(II) anticancer drugs such as oxaliplatin, carboplatin, and cisplatin, in vitro and in vivo studies indicate that the MNPs are more active and show low systemic activity while also possessing emissive properties that allow for fluorescence-based imaging. This pioneering example of a metallacage that combines biologically active components with AIE imaging establishes supramolecular coordination complexes imbedded within nanoparticles as a promising potential theranostic platform for cancer treatment.

Preparation and Evaluation of Quercetin-Loaded MPEG-PLA Nanoparticles

2018 ◽  
Vol 14 (5) ◽  
pp. 366-376 ◽  
Author(s):  
Hiraku Onishi ◽  
Masashi Nakamura ◽  
Masanaho Sasatsu
Keyword(s):  
Organic Solvent ◽  
Therapeutic Potential ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
The Body ◽  
In Vivo Studies ◽  
Water Mixture ◽  
Biodistribution Studies

Background: Quercetin (QE) is one of the flavonoids with various biological functions such as anti-oxidation, anti-inflammatory and antitumor. However, the low aqueous solubility and short half-life in the body reduce its in vivo efficacy. Therefore, the appropriate delivery techniques to solve those problems have drawn much attention. In the present study, methoxypolyethylene glycol- poly-DL-lactic acid (MPEG-PLA) nanoparticles loaded with quercetin (QE), called NP, were prepared, and their antitumor characteristics were investigated in vitro and in vivo. Method: NPs were produced by evaporating organic solvent from the organic solvent-water mixture in four formulations. The particle characteristics and in vitro release were examined for the obtained preparations (NP1 – NP4). The antitumor features were investigated in vivo with different administration schedules using mice inoculated subcutaneously with murine Sarcoma 180. In addition, the efficacy of co-administration of NP with a strong antitumor chemotherapeutic agent, irinotecan hydrochloride (CPT-11), was examined. Biodistribution studies were performed using the same animal models. Result: The NP with the higher drug content (0.58 % (w/w)) and gradual release profile, Preparation NP4, were chosen and used as NP in the in vivo studies. NP suppressed tumor growth better than QE solution in various dosing schedules (total dose = 2 mg/kg). In the combination therapy with CPT-11, NP exhibited antitumor efficacy in a nearly additive manner. No decrease in body weight observed with any administration. NP markedly enhanced the systemic distribution and tumor localization. Conclusion: These results indicated that the present NP should promote the efficacy of QE, and might have useful therapeutic potential in the treatment of solid tumors.

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