99mTc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study

Essa, Basma M.; Sakr, Tamer M.; Khedr, Mohammed A.; El‐Essawy, Farag A.; El-Mohty, A. A.

doi:10.1016/j.ejps.2015.05.002

Cited by 46 publications

(14 citation statements)

References 31 publications

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“…The radiochemical yield of 99m Tc-ZT was estimated using ascending paper chromatography and thin layer chromatography. A dual solvent systems consisting of acetone and ethanol:water:ammonium hydroxide mixture (2:5:1, v/v/v) were used as mobile phases (Essa et al, 2015). The optimized radiolabeled-drug complex was assessed for in-vitro stability.…”

Section: Radio-labeling Of Ztmentioning

confidence: 99%

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

et al. 2016

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Migraine attack is a troublesome physiological condition associated with throbbing, intense headache, in one half of the head. Zolmitriptan is a potent second-generation triptan, prescribed for patients with migraine attacks, with or without an aura, and cluster headaches. The absolute bioavailability of zolmitriptan is about 40% for oral administration; due to hepatic first metabolism. Nasal administration would circumvent the pre-systemic metabolism thus increasing the bioavailability of zolmitriptan. In addition, due to the presence of microvilli and high vasculature, the absorption is expected to be faster compared to oral route. However, the bioavailability of nasal administered drugs is particularly restricted by poor membrane penetration. Thus, the aim of this work is to explore the potential of novel nanovesicular fatty acid enriched structures (novasomes) for effective and enhanced nasal delivery of zolmitriptan and investigate their nose to brain targeting potential. Novasomes were prepared using nonionic surfactant, cholesterol in addition to a free fatty acid. A 2 3 full factorial design was adopted to study the influence of the type of surfactant, type of free fatty acid and ratio between the free fatty acid and the surfactant on novasomes properties. The particle size, entrapment efficiency, polydispersity index, zeta potential and % zolmitriptan released after 2 h were selected as dependent variables. Novasomes were further optimized using Design Expert Õ software (version 7; Stat-Ease Inc., Minneapolis, MN), and an optimized formulation composed of Span Õ 80:Cholesterol:stearic acid (in the ratio 1:1:1) was selected. This formulation showed zolmitriptan entrapment of 92.94%, particle size of 149.9 nm, zeta potential of À55.57 mV, and released 48.43% zolmitriptan after 2 h. The optimized formulation was further examined using transmission electron microscope, which revealed non-aggregating multi-lamellar nanovesicles with narrow size distribution. DSC, XRD examination of the optimized formulation confirmed that the drug have been homogeneously dispersed throughout the novasomes in an amorphous state. In-vivo bio-distribution studies of 99m Tc radio-labeled intranasal zolmitriptan loaded novasomes were done on mice, the pharmacokinetic parameters were compared with those following administration of intravenous 99m Tc-zolmitriptan solution. Results revealed the great enhancement in zolmitriptan targeting to the brain, with drug targeting potential of about 99% following intranasal administration of novasomes compared with the intravenous drug solution. Zolmitriptan loaded novasomes administered via the nasal route may therefore constitute an advance in the management of acute migraine attacks.

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Section: Radio-labeling Of Ztmentioning

confidence: 99%

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

et al. 2016

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“…Direct labeling technique was used to radiolabel phosphinothricin by 99m Tc under reductive conditions using SnCl 2 ·2H 2 O as a reducing agent [ 28 ]. Different labeling reactions were done in evacuated 10 mL penicillin vials to determine the optimum labeling conditions.…”

Section: Methodsmentioning

confidence: 99%

In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity

et al. 2018

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l-Phosphinothricin (glufosinate or 2-amino-4-((hydroxy(methyl) phosphinyl) butyric acid ammonium salt (AHPB)), which is a structural analog of glutamate, is a recognized herbicide that acts on weeds through inhibition of glutamine synthetase. Due to the structural similarity between phosphinothricin and some bisphosphonates (BPs), this study focuses on investigating the possibility of repurposing phosphinothricin as a bisphosphonate analogue, particularly in two medicine-related activities: image probing and as an anti-cancer drug. As BP is a competitive inhibitor of human farnesyl pyrophosphate synthase (HFPPS), in silico molecular docking and dynamic simulations studies were established to evaluate the binding and stability of phosphinothricin with HFPPS, while the results showed good binding and stability in the active site of the enzyme in relation to alendronate. For the purpose of inspecting bone-tissue accumulation of phosphinothricin, a technetium (99mTc)–phosphinothricin complex was developed and its stability and tissue distribution were scrutinized. The radioactive complex showed rapid, high and sustained uptake into bone tissues. Finally, the cytotoxic activity of phosphinothricin was tested against breast and lung cancer cells, with the results indicating cytotoxic activity in relation to alendronate. All the above results provide support for the use of phosphinothricin as a potential anti-cancer drug and of its technetium complex as an imaging probe.

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“…Radiolabeling of doxorubicin with 99m Tc was done by direct technique under reductive conditions using SnCl2.2H2O [53]. Labeling reaction was done by adding 1 mL of doxorubicin solution in DMSO (0.5-2 mg doxorubicin) in an evacuated 10 mL penicillin vial.…”

Section: Radiolabeling Of Doxorubicin Using 99m Tcmentioning

confidence: 99%

Preparation, Characterization, Cytotoxicity and Biological Evaluation of <sup>99m</sup>Tc-Doxorubicin-Epigallocatechingallate Functionalized Gold Nanoparticles as a New Generation of Theranostic Radiopharmaceutical

Sakr¹,

Morsy²,

Na³

et al. 2018

Preprint

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Gold nanoparticles are currently used for the treatment of cancer through a myriad of modalities and delivery approaches. Conjugation of tumor imaging Single Photon Emitting Computed Tomographic (SPECT) radiopharmaceutical to gold nanoparticles will allow systemic targeting and imaging of cancer tissues simultaneously. In this study, gold nanoparticles (AuNPs) were prepared using Epigallocatechingallate (EGCG), loaded with doxorubicin (Dox), and characterized before and after doxorubicin conjugation. Cytotoxicity of EGCG-AuNPs and Dox-EGCG-AuNPs were evaluated against breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) cell lines demonstrating high cytotoxic effects of Dox-EGCG-AuNPs against both cell lines. Doxorubicin was radiolabeled with 99mTc and our new approach has optimized various labeling conditions resulting in a radiochemical yield of 93.5 ± 2.04%. Biodistribution of 99mTc-Dox-EGCG-AuNPs was studied in normal and tumor bearing mice following I.V. and intratumoral injections at different time intervals. Results showed high uptake of the intravenously injected 99mTc-Dox-EGCG-AuNPs in tumor tissue (22.45 %ID/g at 2 h). In addition, localized intratumoral injection of 99mTc-Dox-EGCG-AuNPs showed extremely high levels of uptake in tumor (80.22 %ID/g at 15 min) with high retention for extended periods post injection. Our results present prospects for the utility of 99mTc-Dox-EGCG-AuNPs as a multiplexed theranostic agent through SPECT imaging of tumor tissue and therapy through photothermal destruction of cancer tissue through the application of exogenous laser lights as well as through tyrosine phosphatases inhibitor (through EGCG), and topoisomerase II inhibitor (through doxorubicin) effects.

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99mTc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study

Cited by 46 publications

References 31 publications

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency

In Silico-Based Repositioning of Phosphinothricin as a Novel Technetium-99m Imaging Probe with Potential Anti-Cancer Activity

Preparation, Characterization, Cytotoxicity and Biological Evaluation of <sup>99m</sup>Tc-Doxorubicin-Epigallocatechingallate Functionalized Gold Nanoparticles as a New Generation of Theranostic Radiopharmaceutical

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