M. A. Motaleb

Labeling of ceftriaxone for infective inflammation imaging using 99mTc eluted from 99Mo/99mTc generator based on zirconium molybdate

Zirconium molybdate gel was prepared by mixing (99)Mo, produced from (98)Mo(n,gamma) reaction and Zr solutions in nitrate media with excess H(2)O(2), and used as the base material for (99)Mo/(99m)Tc generator. The prepared generator showed a good performance. (99m)Tc eluted from the prepared generator passed the quality control tests with specifications meeting the requirements of European and US Pharmacopeias. The (99m)Tc eluate was used for labeling of cephalosporin analogue, ceftriaxone, which was then assessed for infection imaging in a mouse model. (99m)Tc-ceftriaxone was prepared at pH 9 with a radiochemical yield of 95+/-2% by adding (99m)Tc to 30 mg ceftriaxone in the presence of 50 microg SnCl(2).2H(2)O. Biodistribution studies in mice were carried out using experimentally induced infection in the left thigh using E. coli. Both thighs of the mice were dissected and counted to evaluate the ratio of bacterial infected thigh/contralateral thigh. (99m)Tc-ceftriaxone showed high uptake in the infectious lesion (T/NT =5.6+/-0.6 at 4h post injection). The abscess to normal muscle ratio indicated that (99m)Tc-ceftriaxone could be used for infection imaging. Besides, in vitro studies showed that (99m)Tc-ceftriaxone can differentiate between bacterial infection and sterile inflammation.

Biodistribution of 99mTc‐sunitinib as a potential radiotracer for tumor hypoxia imaging

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 (99m)Tc-sunitinib radiotracer and to study its tumor binding specificity as a novel selective radiopharmaceutical for tumor hypoxia imaging. The in vivo biodistribution of (99m)Tc-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 (99m)Tc-sunitinib is ready to go through the clinical trials as a potential selective radiotracer able to image tumor hypoxia.

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.

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.