Browsing by Author "Sakr, TM"

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99mTc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study
(Elsevier, 2015) Essa, BM; Sakr, TM; A Khedr, Mohammed; El-Essawy, FA; El-Mohty, AA
Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with 99mTc) with high in silico affinity. The novel prepared 99mTc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors. 99mTc-amitrole was radio-synthesized with a high radiochemical yield (89.7 ± 3.25). It showed in vitro stability for up to 6 h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60 min post-injection. The data described previously could recommend 99mTc-amitrole as potential targeting scintigraphic probe for solid tumor imaging
99mTc–meropenem as a potential SPECT imaging probe for tumor hypoxia
(SPRINGER, 2012) Sakr, TM; Motaleb, MA; Ibrahim, IT
Meropenem was successfully radiolabeled with 99mTc in high labeling yield (92 ± 2%) and stability (~6 h). 99mTc–meropenem showed high accumulation in tumor hypoxic tissue (4.193% injected dose/g organ). 99mTc–meropenem showed high ability to differentiate the tumor tissue from inflamed or infected tissues in different mice models as its T/NT ratio ~4 in case of tumor mice model while T/NT ratio ~1 in case of inflamed mice model. So, 99mTc–meropenem showed high selectivity in comparison with FDG-PET and 99mTc-nitroimidazole analogues. Thus, 99mTc–meropenem could be used as a selective potential imaging agent for diagnosis of tumor hypoxia.
99mTc-nebivolol as a novel heart imaging radiopharmaceutical for myocardial infarction assessmenta
(SPRINGER, 2013) Sakr, TM; Moustapha, ME; Motaleb, MA
Non-invasive quantification of myocardial β-receptors could become an independent prognostic marker for chronic heart failure and cardiovascular disorders. The aim of this study was to formulate a novel radiopharmaceutical for the detection of myocardial infarction at early stages in susceptible patients, which requires the development of high myocardium affinity radiopharmaceuticals able to establish an accurate in vivo quantification of cardiac β1-adrenoceptors. This was attained by the direct complexation of nebivolol as a cardioselective agent with technetium-99m as one of the most useful radionuclides in diagnostic nuclear medicine. Factors affecting the radiochemical yield such as nebivolol amount, stannous chloride amount, reaction time and pH of the reaction mixture were optimized. The results showed that the radiochemical yield was 95 ± 2.87 % and the radiolabeled compound was separated by high performance liquid chromatography. In vitro studies showed that the formed complex was stable for up to 24 h. In vivo uptake of 99mTc-nebivolol in the heart was 4.55 ± 0.23 % ID/g organ at 0.5 h post injection, whereas the clearance from Albino mice appeared to proceed via the hepatobiliary and renal clearance pathways. Predosing mice with cold nebivolol reduced the heart uptake to 1.1 ± 0.02 % and further confirmed the high specificity and selectivity of this radiotracer for the assessment of the myocardial β1-adrenoceptors
Biodistribution of 99mTc‐sunitinib as a potential radiotracer for tumor hypoxia imaging
(WILEY, 2013) Sakr, TM; El‐Safoury, DM; AS Awad, Gehanne; Motaleb, MA
Tyrosine kinases are groups of enzymes, which are over‐expressed in solid tumor cells, representing good targets for different drugs such as sunitinib (N‐[2‐(diethylamino)ethyl]‐5‐{[(3Z)‐5‐fluoro‐2‐oxo‐2,3‐dihydro‐1H‐indol‐3‐ylidene]methyl}‐2,4‐dimethyl‐1H‐pyrrole‐3‐carboxamide). The aim of this work was to design and synthesize 99mTc‐sunitinib radiotracer and to study its tumor binding specificity as a novel selective radiopharmaceutical for tumor hypoxia imaging. The in vivo biodistribution of 99mTc‐sunitinib in tumor bearing mice showed high target/non‐target (T/NT) ratio (T/NT ~ 3 at 60 min post injection). This preclinical high biological accumulation in tumor cells suggests that 99mTc‐sunitinib is ready to go through the clinical trials as a potential selective radiotracer able to image tumor hypoxia.
Formulation and preclinical evaluation of 99mTc–gemcitabine as a novel radiopharmaceutical for solid tumor imaging
(SPRINGER, 2014) Ibrahim, AB; Sakr, TM; Khoweysa, OMA; Motaleb, MA; El-Kolaly, MT
The aim of this study is the formulation of a new radiopharmaceutical for imaging solid tumor bearing. Gemcitabine is a nucleoside analogue used as chemotherapeutic agent. Gemcitabine was formulated and radiolabeled with one of the most important diagnostic radioactive isotopes (technetium-99m) to be investigated in solid tumor imaging. The labeling parameters such as gemcitabine amount, stannous chloride amount, pH of the reaction mixture, and reaction time were optimized. 99mTc–gemcitabine was prepared at pH 9 with a maximum labeling yield of 96 ± 0.3 % without any notable decomposition at room temperature over a period of 8 h. The preclinical evaluation and biodistribution in solid tumor bearing mice showed that 99mTc–gemcitabine had solid tumor selectivity, preclinical high biological accumulation in tumor cells and high retention. Tumor/normal muscle (T/NT) ratios increased with time showing high T/NT ratio (T/NT = 4.9 ± 0.27 at 120 min post injection) and high Tumor/Blood ratio (3.4 ± 0.06), suggesting 99mTc–gemcitabine as a novel solid tumor imaging agent
In silico study and biological evaluation of 99mTc-tricabonyl oxiracetam as a selective imaging probe for AMPA receptors
(SPRINGER, 2017) Sanad, MH; Sakr, TM; HA Abdel-Hamid, Walaa; Marzook, EA
The non-invasive quantification of AMPA receptors (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) could become a prognostic marker for brain disorders. 99mTc-tricarbonyl oxiracetam complex was prepared as a novel probe for AMPA receptor targeting with radiolabeling yield >98% and showed stability of 12 h. Molecular modeling and docking studies of 99mTc-tricarbonyl oxiracetam were performed. The results suggested that the complex act as very good positive allosteric modulators for AMPA receptor. The biodistribution studies revealed high brain uptake (7.5 ± 0.11% %ID/g) at 5 min post-I.V. injection that make 99mTc-tricarbonyl oxiracetam as a novel brain perfusion imaging radiotracer.
Preliminary assessment of radioiodinated fenoterol and reproterol as potential scintigraphic agents for lung imaging
(SPRINGER, 2015) Swidan, MM; Sakr, TM; Motaleb, MA; Abd El-Bary, A; El-Kolaly, MT
Radioiodinated fenoterol and reproterol were prepared by electrophilic radioiodination reaction using chloramin-T as oxidizing agent with radiochemical yields of 97.7 ± 0.7 and 95.2 ± 0.3 %, respectively, and in vitro stability up to 72 h. Biodistribution study performed in male Albino Swiss mice showed maximum radioactivity accumulation in lungs tissue to the extent of 52 ± 1.03 and 50.6 ± 1.2 % ID/g at 15 and 30 min post injection (p.i.) for radioiodinated fenoterol and reproterol, respectively, with low accumulation in heart and blood. The clearance pathway of both iodo-compounds was through renal and hepatobiliary routes. The selectivity of iodo-compounds to lung was examined by in vivo receptor blocking study. Radioiodinated fenoterol and reproterol are not a blood products and so they are more safer than the currently available 99mTc-MAA, and their lungs uptake is higher than that of the recently discovered 125/123I-IPMPD, 99mTc(CO)5I, 99mTc-DHPM and 125/123I-paroxetine. So, radioiodinated fenoterol and reproterol could be introduced as a new compromising radiopharmaceuticals for lung perfusion scintigraphy more safe than the currently available 99mTc-MAA and more potential than the recently discovered 125/123I-IPMPD, 99mTc(CO)5I, 99mTc-DHPM and 125/123I-paroxetine
Preparation and evaluation of nano-crystalline titania as sorbent for 99Mo/99mTc generator
(Taylor & Francis, 2016) Fasih, TW; Sakr, TM; Ayoub, RR; Amin, M
In the presented work, nano-crystalline titania (TiO2) was synthesized and evaluated as a novel chromatographic sorbent for the preparation of the medical 99Mo/99mTc generator. TiO2 was synthesized by dissolving TiCl4.6H2O with isopropyl alcohol to form a semisolid mass that was extensively dried and washed. The physicochemical parameters and surface area of the synthesized nano-crystalline TiO2 were evaluated. TiO2 was packed as a chromatographic column to study the sorption of 99Mo-polymolybdate (VI) anionic solution by dynamic equilibrium. The maximum sorption capacity of 99Mo was ~141±2mg Mo/g TiO2, thereby confirming its suitability for using low specific activity 99Mo for the preparation of 99Mo/99mTc generator. The elution performance of the prepared 99Mo/99mTc generator based on Ti-99Mo was evaluated. It showed high radiochemical purity (≥ 97% TcO4−), high radionuclidic purity (≥ 99.99%99mTc) and high chemical purity; all of these specifications show the suitability for use in nuclear medicine applications.
Radioiodinated acebutolol as a new highly selective radiotracer for myocardial perfusion imaging
(Journal of Labelled Compounds and Radiopharmaceuticals, 2014) Swidan, MM; Sakr, TM; Motaleb, MA; Abd El‐Bary, A; El‐Kolaly, MT
Acebutolol was successfully labeled with 125I via direct electrophilic substitution reaction. Radioiodinated acebutolol was prepared with a maximum radiochemical yield of 96.5 ± 0.3% and in vitro stability up to 72 h. The in vivo biological distribution of radioiodinated acebutolol showed high heart uptake of 37.8 ± 0.14% injected activity/g organ with low lungs and liver uptakes at 5 min post‐injection. In vivo receptor blocking study was carried out in mice to evaluate its selectivity to heart. Radioiodinated acebutolol showed fast heart accumulation with high heart/liver ratio, which provides the ability for fast myocardial imaging with significant decrease in the radiation hazards risk on patients. So, radioiodinated acebutolol could be displayed as a radiotracer drug of choice in case of emergency patients for myocardial perfusion imaging.
Radioiodinated anastrozole and epirubicin as potential targeting radiopharmaceuticals for solid tumor imaging
(SPRINGER, 2015) Ibrahim, AB; Sakr, TM; Khoweysa, OMA; Motaleb, MA; Abd El-Bary, A; El-Kolaly, MT
This study describes the preparation of radioiodinated anastrozole and epirubicin and their biological evaluation as potential solid tumor imaging gents. Radioiodinated anastrozole and epirubicin were successfully prepared via direct electrophilic substitution reaction at ambient temperature. The radiochemical yields for radioiodinated anastrozole and epirubicin were maximized to 92.9 ± 0.1 and 98.8 ± 0.1 %, respectively by studying different reaction parameters such as substrate amount, chloramine-T, pH of the reaction mixture, reaction temperature and reaction time. They showed in vitro stability up to 4 and 24 h, respectively. The preclinical evaluation and biodistribution in mice bearing solid tumor showed high retention and biological accumulation in solid tumor cells (12.4 and 25.3 % injected activity/g tissue) and high T/NT ratio equal to 4.7 ± 0.1 and 5.2 ± 0.1 at 2 and 1 h post-injection, respectively. Data described before could recommend radioiodinated anastrozole and radioiodinated epirubicin as potential targeting radiopharmaceuticals for solid tumor imaging
Synthesis and biodistribution of 99mTc-PyDA as a potential marker for tumor hypoxia imaging
(SPRINGER, 2014) Sakr, TM; Essa, BM; El-Essawy, FA; El-Mohty, AA
The 99mTc-pyrimidine-4,5-diamine (99mTc-PyDA) complex was prepared. The yield under the optimum conditions (5 mg of PyDA, pH 8, 25 μg of SnCl2·2H2O) was 96 ± 3%. The complex is stable in vitro for 24 h. The complex was tested on mice as potential marker for tumor hypoxia imaging. The complex showed high tumor hypoxia uptake with the target/nontarget (T/NT) ratio as high as ∼3.
Synthesis and preclinical pharmacological evaluation of 99mTc‐TEDP as a novel bone imaging agent
(John Wiley & Sons, Ltd., 2011) Motaleb, MA; Sakr, TM
The detection of bone metastasis in early stages requires the development of high‐affinity bone imaging radiopharmaceuticals for the improvement of the diagnostic accuracy of routine bone scanning and effective management of these medical cases. This study aimed to provide a convenient synthesis of 1‐thioethylidene‐l,l‐disodiumphosphonate (TEDP) and an improved preparation of its 99mTc‐TEDP complex. The results showed that the radiochemical purity of 99mTc‐TEDP was found to be 95 ± 2% and that its stability was up to 6 h. Biodistribution study showed high and long uptake of 99mTc‐TEDP in bone starting from 15 min (39 ± 4 ID/g) to 3 h (53 ± 2.4 ID/g) showing high affinity of 99mTc‐TEDP complex to bones. This research could introduce a novel radiopharmaceutical that could be used in scanning body bones starting from 15 min between injection of 99mTc‐TEDP and bone imaging, minimizing the burden on patients in terms of the total length of the examination and the dose of radiation absorbed and showing high specificity and efficacy in bone scintigraph
Synthesis and preliminary affinity testing of 123I/125I-N-(3-iodophenyl)-2-methylpyrimidine-4,6-diamine as a novel potential lung scintigraphic agen
(SPRINGER, 2014) Sakr, TM
Radioiodinated N-(3-iodophenyl)-2-methylpyrimidine-4,6-diamine (radioiodinated IPMPD), a potential lung scintigraphic agent, was synthesized via direct electrophilic substitution. Factors affecting the radiochemical yield were studied in detail. High radiochemical yield (92.3 ± 2.3%) was reached. The compound is stable in vitro for 24 h. Radioiodinated IPMPD was biologically evaluated in normal Albino mice. The compound demonstrated high lung uptake (21.4 ± 1.7% of injected dose per gram organ at 15 min) and thus shows promise for lung perfusion scintigraphy
Synthesis, radioiodination and in vivo evaluation of ethyl 1,4-dihydro-7-iodo-4-oxoquinoline-3-carboxylate as a potential pulmonary perfusion scintigraphic radiopharmaceutical
(SPRINGER, 2015) Sakr, TM; Motaleb, MA; Zaghary, WA
The goal of this study was to biologically evaluate a newly synthesized radioiodinated ethyl 1,4-dihydro-7-iodo-4-oxoquinoline-3-carboxylate (EIOQC) as a potential lung scintigraphic agent. EIOQC was synthesized, characterized then radioiodinated via direct electrophilic substitution reaction. Factors affecting the radiochemical purity were studied in details and the biological distribution of the radioiodinated compound was evaluated in normal male Albino mice. EIOQC was successfully synthesized and radioiodinated with high radiochemical purity (96 ± 1.21 %) and in vitro stability up to 48 h. The biological evaluation of radioiodinated EIOQC showed high lung affinity of 21.36 ± 1.73 % injected dose/g organ (% ID/g) at 15 min. This study introduces radioiodinated EIOQC as a novel potential radiopharmaceutical for lung perfusion scintigraphy