Iron oxide nanoparticulate system as a cornerstone in the effective delivery of Tc-99 m radionuclide: a potential molecular imaging probe for tumor diagnosis

Abstract

Background The evolution of nanoparticles has gained prominence as platforms for developing diagnostic and/or therapeutic radiotracers. This study aims to develop a novel technique for fabricating a tumor diagnostic probe based on iron oxide nanoparticles excluding the utilization of chelating ligands. Methods Tc-99 m radionuclide was loaded into magnetic iron oxide nanoparticles platform (MIONPs) by sonication. 99m Tcencapsulated MIONPs were fully characterized concerning particles size, charge, radiochemical purity, encapsulation efficiency, in-vitro stability and cytotoxicity. These merits were biologically evaluated in normal and solid tumor bearing mice via different delivery approaches. Results 99m Tc-encapsulated MIONPs probe was synthesized with average particle size 24.08 ± 7.9 nm, hydrodynamic size 52 nm, zeta potential -28 mV, radiolabeling yield 96 ± 0.83%, high in-vitro physiological stability, and appropriate cytotoxicity behavior. The in-vivo evaluation in solid tumor bearing mice revealed that the maximum tumor radioactivity accumulation (25.39 ± 0.57, 36.40 ± 0.59 and 72.61 ± 0.82%ID/g) was accomplished at 60, 60 and 30 min p.i. for intravenous, intravenous with physical magnet targeting and intratumoral delivery, respectively. The optimum T/NT ratios of 57.70, 65.00 and 87.48 were demonstrated at 60 min post I.V., I.V. with physical magnet targeting and I.T. delivery, respectively. These chemical and biological characteristics of our prepared nano-probe demonstrate highly advanced merits over the previously reported chelator mediated radiolabeled nano-formulations which reported maximum tumor uptakes in the scope of 3.65 ± 0.19 to 16.21 ± 2.56%ID/g. Conclusion Stabilized encapsulation of 99m Tc radionuclide into MIONPs elucidates a novel strategy for developing an advanced nano-sized radiopharmaceutical for tumor diagnosis.

pH-Sensitive doxorubicin delivery using zinc oxide nanoparticles as a rectified theranostic platform: in vitro anti-proliferative, apoptotic, cell cycle arrest and in vivo radio-distribution studies

“…as a result of their nature of being leaky vasculature tissues. 72–74 In regard to group B, the in vivo distribution in tumor-induced mice disclosed a climbing accumulation in the tissues of the tumor at an optimal uptake of 14 ± 0.8% ID g −1 at 1 h p.i. and then steadily fell down to its lowest value of 2.8 ± 0.6% ID g −1 at 4 h p.i.…”

Multi-functionalization of reduced graphene oxide nanosheets for tumor theragnosis: Synthesis, characterization, enzyme assay, in-silico study, radiolabeling and in vivo targeting evaluation

“…High uptake with long retention and two folds increased uptake of the radioactivity in short time assured that; the designed nanosheets played a major role in selective accumulation of the radioactivity at tumor site. Also, the tumor uptake was further augmented by EPR phenomena [ 9 , 68 – 71 ]. In addition, tumor tissues lose a disposal lymphatic system, which enhanced the retention of 99m Tc-NGO-COOH-3.…”

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery

“…In this review, we present inorganic NPs that are synthesized using reducing and stabilizing agents where the reducing agent is responsible for the reduction of the metal from high oxidation states (+3, +2 or +1) to its metallic form (zero oxidation state), while the stabilizing agent is responsible for surface stabilization of metal nano materials [ 22 , 42 , 44 , 45 , 47 , 49 , 50 , 52 ]. Various NPs including AuNPs, selenium nanoparticles (SeNP), iron nanoparticles (FeNP), copper nanoparticles (CuNP) and silver nanoparticles (AgNP) were evaluated for their effective delivery of different radionuclides such as tecnetium-99m (Tc-99m), iodine-131 (I-131) and gold-198 (Au-198) to tumor sites for tumor theranostics [ 42 , 44 , 45 , 47 , 48 , 49 , 50 , 51 , 52 , 72 ].…”