The aim of this study was to develop a dual-modality PET/MR imaging probe by radiolabeling iron oxide magnetic nanoparticles (IONPs), surface functionalized with water soluble stabilizer 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), with the positron emitter Gallium-68. Magnetite nanoparticles (Fe3O4 MNPs) were synthesized via coprecipitation method and were stabilized with DPD. The Fe3O4-DPD MNPs were characterized based on their structure, morphology, size, surface charge, and magnetic properties. In vitro cytotoxicity studies showed reduced toxicity in normal cells, compared to cancer cells. Fe3O4-DPD MNPs were successfully labeled with Gallium-68 at high radiochemical purity (>91%) and their stability in human serum and in PBS was demonstrated, along with their further characterization on size and magnetic properties. The ex vivo biodistribution studies in normal Swiss mice showed high uptake in the liver followed by spleen. The acquired PET images were in accordance with the ex vivo biodistribution results. Our findings indicate that 68Ga-Fe3O4-DPD MNPs could serve as an important diagnostic tool for biomedical imaging.
Development of a
complex based on iron oxide nanoparticles (IONPs) for diagnosis and
dual magnetic hyperthermia/radionuclide cancer therapy accomplishing
high yields of radiolabeling and great magnetic heat induction is
still a challenge. We report here the synthesis of citric acid, poly(acrylic
acid) (PAA) and poly(ethylene glycol) coated IONPs and their labeling
with three radionuclides, namely, technetium (99mTc), yttrium
(90Y), and lutetium (177Lu), aiming at potential
use in cancer diagnosis and therapy. Polyol-synthesized IONPs are
a flowerlike structure with 13.5 nm spherically shaped cores and 24.8
nm diameter. PAA-coated nanoparticles (PAA@IONP) showed the best characteristics
such as easy radiolabeling with very high yields (>97.5%) with
all three radionuclides, and excellent in vitro stabilities with less
than 10% of radionuclides detaching after 24 h. Heating ability of
PAA@IONP in an alternating external magnetic field showed intrinsic
loss power value of 7.3 nH m2/kg, which is one of higher
reported values. Additionally, PAA@IONP itself presented no significant
cytotoxicity to the CT-26 cancer cells, reaching IC50 at 60 μg/mL.
However, under the external magnetic field, they show hyperthermia-mediated
cells killing, which correlated with the magnetic field strength and
time of exposure. Since PAA@IONP are easy to prepare, biocompatible,
and with excellent magnetic heat induction, these nanoparticles radiolabeled
with high-energy beta emitters 90Y and 177Lu
have valuable potential as agent for dual magnetic hyperthermia/radionuclide
therapy, while radiolabeled with 99mTc could be used in
diagnostic imaging.
Two different types of magnetic nanoparticles (MNPs) were synthesized in order to compare their efficiency as radioactive vectors, Fe₃O₄-Naked (80 ± 5 nm) and polyethylene glycol 600 diacid functionalized Fe₃O₄(Fe₃O₄-PEG600) MNPs (46 ± 0.6 nm). They were characterized based on the external morphology, size distribution, and colloidal and magnetic properties. The obtained specific power absorption value for Fe₃O₄-PEG600 MNPs was 200 W/g, indicated their potential in hyperthermia based cancer treatments. The labeling yield, in vitro stability and in vivo biodistribution profile of (90) Y-MNPs were compared. Both types of MNPs were (90)Y-labeled in reproducible high yield (>97%). The stability of the obtained radioactive nanoparticles was evaluated in saline and human serum media in order to optimize the formulations for in vivo use. The biodistribution in Wistar rats showed different pharmacokinetic behaviors of nanoparticles: a large fraction of both injected MNPs ended in the liver (14.58%ID/g for (90)Y-Fe₃O₄-Naked MNPs and 19.61%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) whereas minor fractions attained in other organs. The main difference between the two types of MNPs was the higher accumulation of (90)Y-Fe₃O₄-Naked MNPs in the lungs (12.14%ID/g vs. 2.00%ID/g for (90)Y-Fe₃O₄-PEG600 MNPs) due to their in vivo agglomeration. The studied radiolabeled magnetic complexes such as (90)Y-Fe₃O₄-PEG600 MNPs constitute a great promise for multiple diagnostic-therapeutic uses combining, for example, MRI-magnetic hyperthermia and regional radiotherapy.
Radiolabeled albumin microspheres with encapsulated citric acid-coated magnetite nanoparticles were developed as a targeting approach to localize both radioactivity and magnetic energy at the tumor site. We present in vitro and in vivo studies of yttrium-90 ( 90 Y)-labeled human serum albumin magnetic microspheres (HSAMMS) as a multifunctional agent for possible applications in a bimodal radionuclide-hyperthermia cancer therapy. The HSAMMS were produced using a modified emulsification-heat stabilization technique and contained 11 nm magnetite nanoparticles coated with citric acid, distributed as inhomogeneous clusters within the albumin microspheres. The size, size distribution and the morphology of magnetite nanoparticles and HSAMMS were determined by FESEM, HRTEM and SEM/FIB dual beam. The average particle size of the complete HSAMMS was 20 mm, and they exhibited superparamagnetic behavior at room temperature. The in vitro experiments (in saline and human serum) revealed the high stability of the labeled HSAMMS in saline and human serum after 72 h. Following the intravenous administration of the 90 Y-HSAMMS in rats, 88.81% of the activity localizes in the lungs after 1 h, with 82.67% remaining after 72 h. These data on 90 Y-HSAMMS provide good evidence for their potential use in bimodal radionuclide-hyperthermia cancer therapy.
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