Dataset Information

Tumor targeting using magnetic nanoparticle Hsp70 conjugate in a model of C6 glioma.

ABSTRACT:

Background

Superparamagnetic iron oxide nanoparticles (SPIONs), due to their unique magnetic properties, have the ability to function both as magnetic resonance (MR) contrast agents, and can be used for thermotherapy. SPIONs conjugated to the heat shock protein Hsp70 that selectively binds to the CD40 receptor present on glioma cells, could be used for MR contrast enhancement of experimental C6 glioma.

Methods

The magnetic properties of the Hsp70-SPIONs were measured by NMR relaxometry method. The uptake of nanoparticles was assessed on the C6 glioma cells by confocal and electron microscopes. The tumor selectivity of Hsp70-SPIONs being intravenously administered was analyzed in the experimental model of C6 glioma in the MRI scanner.

Results

Hsp70-SPIONs relaxivity corresponded to the properties of negative contrast agents with a hypointensive change of resonance signal in MR imaging. A significant accumulation of the Hsp70-SPIONs but not the non-conjugated nanoparticles was observed by confocal microscopy within C6 cells. Negative contrast tumor enhancement in the T2-weighted MR images was higher in the case of Hsp70-SPIONs in comparison to non-modified SPIONs. Histological analysis of the brain sections confirmed the retention of the Hsp70-SPIONs in the glioma tumor but not in the adjacent normal brain tissues.

Conclusion

The study demonstrated that Hsp70-SPION conjugate intravenously administered in C6 glioma model accumulated in the tumors and enhanced the contrast of their MR images.

SUBMITTER: Shevtsov MA

PROVIDER: S-EPMC3870835 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Publications

Tumor targeting using magnetic nanoparticle Hsp70 conjugate in a model of C6 glioma.

Shevtsov Maxim A MA Yakovleva Ludmila Y LY Nikolaev Boris P BP Marchenko Yaroslav Y YY Dobrodumov Anatolii V AV Onokhin Kirill V KV Onokhina Yana S YS Selkov Sergey A SA Mikhrina Anastasiia L AL Guzhova Irina V IV Martynova Marina G MG Bystrova Olga A OA Ischenko Alexander M AM Margulis Boris A BA

Neuro-oncology 20131204 1

<h4>Background</h4>Superparamagnetic iron oxide nanoparticles (SPIONs), due to their unique magnetic properties, have the ability to function both as magnetic resonance (MR) contrast agents, and can be used for thermotherapy. SPIONs conjugated to the heat shock protein Hsp70 that selectively binds to the CD40 receptor present on glioma cells, could be used for MR contrast enhancement of experimental C6 glioma.<h4>Methods</h4>The magnetic properties of the Hsp70-SPIONs were measured by NMR relaxo ...[more]

PMID: 24305705

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Project description:UnlabelledThe sodium/iodide symporter (NIS) is under investigation as a reporter for noninvasive imaging of gene expression. Although (18)F-tetrafluoroborate ((18)F-TFB, (18)F-BF4 (-)) has shown promise as a PET imaging probe for NIS, the current synthesis method using isotopic exchange gives suboptimal radiochemical yield and specific activity. The aim of this study was to synthesize (18)F-TFB via direct radiofluorination on boron trifluoride (BF3) to enhance both labeling yield and specific activity and evaluation of specific activity influence on tumor uptake.MethodsAn automated synthesis of (18)F-TFB was developed whereby cyclotron-produced (18)F-fluoride was trapped on a quaternary methyl ammonium anion exchange cartridge, then allowed to react with BF3 freshly preformulated in petroleum ether/tetrahydrofuran (50:1). The resultant (18)F-TFB product was retained on the quaternary methyl ammonium anion exchange cartridge. After the cartridge was rinsed with tetrahydrofuran and water, (18)F-TFB was eluted from the cartridge with isotonic saline, passing through 3 neutral alumina cartridges and a sterilizing filter. Preclinical imaging studies with (18)F-TFB were performed in athymic mice bearing NIS-expressing C6-glioma subcutaneous xenografted tumors to determine the influence of specific activity on tumor uptake.ResultsUnder optimized conditions, (18)F-TFB was synthesized in a radiochemical yield of 20.0% ± 0.7% (n = 3, uncorrected for decay) and greater than 98% radiochemical purity in a synthesis time of 10 min. Specific activities of 8.84 ± 0.56 GBq/μmol (n = 3) were achieved from starting (18)F-fluoride radioactivities of 40-44 GBq. An avid uptake of (18)F-TFB was observed in human NIS (hNIS)-expressing C6-glioma xenografts as well as expected NIS-mediated uptake in the thyroid and stomach. There was a positive correlation between the uptake of (18)F-TFB in hNIS-expressing tumor and specific activity.ConclusionA rapid, practical, and high-specific-activity synthesis of the NIS reporter probe (18)F-TFB was achieved via direct radiofluorination on BF3 using an automated synthesis system. The synthesis of high-specific-activity (18)F-TFB should enable future clinical studies with hNIS gene reporter viral constructs.

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Dataset Information

Tumor targeting using magnetic nanoparticle Hsp70 conjugate in a model of C6 glioma.

Background

Methods

Results

Conclusion

Publications

Tumor targeting using magnetic nanoparticle Hsp70 conjugate in a model of C6 glioma.

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