M. T. El-Kolaly

Radioiodinated acebutolol as a new highly selective radiotracer for myocardial perfusion imaging

Acebutolol was successfully labeled with (125) I 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.

Radioiodination and biological evaluation of Cladribine as potential agent for tumor imaging and therapy

Abstract Cladribine, a purine analogue antimetabolite, was radioiodinated with 125I via direct electrophilic substitution reaction. The maximum radiochemical yield (92.5 ± 0.8%) was obtained when the reaction was done at ambient temperature for 30 min using 100 μg of Cladribine and 10 μg N-chlorosuccinamide (NCS) in 150 μL of 0.2 M phosphate buffer, pH 7. In vitro stability studies of HPLC purified 125I-Cladribine sample dissolved in 0.5 ml of 0.2 M phosphate buffer pH 7 at ambient temperature showed that 125I-Cladribine is stable up to 12 h post labeling. Biodistribution results revealed excretion of 125I-Cladribine mainly by kidneys. The uptake of 125I-Cladribine in the induced Ehrlich Ascites Carcinoma was 2.8 ± 0.4 %ID/g at 1 h post injection with maximum tumor/muscle ratio of 5.5. The good uptake of 125I-Cladribine confirms the molecular docking studies results which indicate that iodinated Cladribine binds with polymerase enzyme with a good –CDOCKER energy. As a result, radioiodinated Cladribine may be used as a valuable agent for tumor diagnosis and therapy.

Preparation of radioiodinated bambuterol hydrochloride as beta receptors imaging agent

Bambuterol·HCl was successfully labeled with 125I via direct electrophilic substitution at ambient temperature. The effect of reaction parameters such as Bambuterol amount, CAT amount, pH of the reaction mixture, reaction temperature, and reaction time and the in vitro stability of 125I-Bambuterol·HCl were studied. The maximum yield of 125I-Bambuterol·HCl was 92.5 ± 1.9%. The yield was determined by paper electrophoresis. In vitro stability study showed that it is preferred to use the freshly prepared agent. Biodistribution studies showed high uptake of 125I-Bambuterol·HCl in liver and lungs (16 ± 0.15 and 4.3 ± 0.08% injected dose/g tissue, respectively, at 5 min post injection). The uptake in liver and lung remained high up to 1 h, as β2-receptors are located mainly at the liver and lungs (bronchial smooth muscles). The clearance of 125I-Bambuterol·HCl from mice appeared to be mainly via the renal pathway. Radioiodinated Bambuterol·HCl shows promise as novel selective β2-adrenoceptor imaging agent.

Laser-responsive liposome for selective tumor targeting of nitazoxanide nanoparticles

ABSTRACT Nitazoxanide [2‐(Acetyloxy)‐N‐(5‐nitro‐2‐thiazolyl)benzamide], usually referred as NTZ, is an antiparasites drug with a potential anti‐cancer reactivity. However, the bioavailability of nitazoxanide is limited due to its poor water solubility. In this study, nitazoxanide could be successfully incorporated in a stable biocompatible liposome (NTZ‐LP) using a modified thin film hydration technique. Further, a novel lipophilic phthalocyanine star polymer R4PcZn was prepared as photosensitizer and in situ incorporated with NTZ in the liposome formulation affording a laser‐responsive liposome (NTZ‐ZnPc‐LP). Both (NTZ‐LP) and (NTZ‐ZnPc‐LP) showed high entrapment efficiency (EE) and high in vitro drug release rates. Transmission electron microscope (TEM) images and dynamic light scattering (DLS) measurements of (NTZ‐LP) and (NTZ‐ZnPc‐LP) showed unilamellar vesicles of mean diameter 192.2 and 87.4 nm, respectively. In addition, NTZ nanoparticles (NTZ NPs) were prepared via membrane extrusion method using DMF and water as solvents. All formulations were similarly prepared using radiolabeled nitazoxanide 125I‐NTZ. After induction of solid tumor in mices using Ehrlich Ascites Carcinoma, the prepared formulations were injected in the tail vein of the mices. Tumor sites of the animal injected with (125I–NTZ‐ZnPc‐LP) were illuminated with a He‐Ne laser (&lgr; = 630 nm). Afterwards, the biodistriburtion of 125I–NTZ was tagged using &ggr; counter. Results showed that the light‐responsive formulation (125I–NTZ‐ZnPc‐LP) affords a higher accumulation of 125I NTZ in the tumor sites after illumination. This can be attributed to the rupture of liposome lipid bilayer as a result of the photosensitization process and the singlet oxygen species resulted thereof. Despite (NTZ NPs) formulation showed a rapid accumulation of NTZ in tumor, it showed unfavoured rapid blood clearance rate. Graphical abstract Figure. No Caption available.

Effect of gamma-radiation on the Sn(II) content, radiochemical purity, in-vitro stability and biological distribution of some99mTc-labelled freeze dried kits

Gamma-irradiation can be used for the sterilization of some99mTc-labelled freeze dried kits. In connection with this the effect of γ-radiation on Sn(II) content, radiochemical purity,in-vitro stability and biological distribution of some currently used99mTc-labelled kits has been investigated. For irradiation the certain radiation sterilization doses (25 and 50 kGy) were used. A variable decrease of Sn(II) content was observed in all γ-irradiated kits. The losses are in the order of 10–25% compared with the Sn(II) content of original ones. The colour of the irradiated kits did not changed except DTPA which developed yellow colour after irradiation. For the irradiated and original kits nearly the same pH were found. The irradiated kits seemed to undergo partial decomposition or chemical alteration which led to some deviation of the biological distribution of them.

Design and development of microemulsion systems of a new antineoplaston A10 analog for enhanced intravenous antitumor activity: In vitro characterization, molecular docking, 125 I-radiolabeling and in vivo biodistribution studies

ABSTRACT A10, (3‐phenylacetylamino‐2,6‐piperidinedione), is a natural peptide with broad antineoplastic activity. Recently, in vitro antitumor effect of a new A10 analog [3‐(4‐methoxybenzoylamino)‐2,6‐piperidinedione] (MPD) has been verified. However, poor aqueous solubility represents an obstacle towards intravenous formulation of MPD and impedes successful in vivo antitumor activity. To surmount such limitation, MPD microemulsion (MPDME) was developed. A 3122 full factorial design using Design‐Expert® software was adopted to study the influence of different parameters and select the optimum formulation (MPDME1). Transmission electron microscopy (TEM) displayed spherical droplets of MPDME1. The cytotoxicity of MPDME1 in Michigan Cancer Foundation 7 (MCF‐7) breast cancer cell line exceeded that of MPD solution (MPDS) and tamoxifen. Compatibility with injectable diluents, in vitro hemolytic studies and in vivo histopathological examination confirmed the safety of parenteral application of MPDME1. Molecular docking results showed almost same binding affinity of A10, MPD and 125I‐MPD with histone deacetylase 8 (HDAC8) receptor. Accordingly, radioiodination of MPDME1 and MPDS was done via direct electrophilic substitution reaction. Biodistribution of 125I‐MPDME1 and 125I‐MPDS in normal and tumor (ascites and solid) bearing mice showed high accumulation of 125I‐MPDME1 in tumor tissues. Overall, the results proved that MPDME represents promising parenteral delivery system capable of improving antineoplastic activity of MPD.

I-131 doping of silver nanoparticles platform for tumor theranosis guided drug delivery

&NA; Nanotechnology may be applied in medicine where the utilization of nanoparticles (≤100 nm) for the delivery and targeting of theranostic agents is at the forefront of projects in cancer nano‐science. This study points a novel one step synthesis approach to build up polyethylene glycol capped silver nanoparticles doped with I‐131 radionuclide (131I‐doped Ag‐PEG NPs). The formula was prepared with average hydrodynamic size 21 nm, zeta potential – 25 mV, radiolabeling yield 98 ± 0.76%, and showed good in‐vitro stability in saline and mice serum. The in‐vitro cytotoxicity study of cold Ag‐PEG NPs formula as a drug carrier vehicle showed no cytotoxic effect on normal cells (WI‐38 cells) at a concentration below 3 &mgr;L/104 cells. The in‐vivo biodistribution pattern of 131I‐doped Ag‐PEG NPs in solid tumor bearing mice showed high radioactivity accumulation in tumor tissues with maximum uptake of 35.43 ± 1.12 and 63.8 ± 1.3% ID/g at 60 and 15 min post intravenous (I.V.) and intratumoral injection (I.T.), respectively. Great potential of T/NT ratios were obtained throughout the experimental time points with maximum ratios 45.23 ± 0.65 and 92.46 ± 1.02 at 60 and 15 min post I.V. and I.T. injection, respectively. Thus, 131I‐doped Ag‐PEG NPs formulation could be displayed as a great potential tumor nano‐sized theranostic probe. Graphical abstract Figure. No caption available.