**7. Conclusion**

An urgent requirement for rapid detection and diagnosis of diseases has led to development of contrast agents and imaging techniques. The present challenge is for fast and complete imaging of tissues and lesion categorization that could be obtained by development of nontoxic contrast agents with longer blood circulation time. Nanotechnology provides apt solution to this problem. Nanoparticle based contrast agents have been employed in most biomedical imaging techniques like MRI, fluorescence imaging, CT, ultrasound, PET and SPECT. However, these imaging techniques have certain limitations. These can be overcome by use of multifunctional nanoplatforms to enhance safety, efficacy and theranostic attributes. The WHO 2016 Classification is a major step forward toward a more precise

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**Author details**

Patiala, India

Dimple Sethi Chopra

Department of Pharmaceutical Sciences and Drug Research, Punjabi University,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: dimplechopra24@yahoo.co.in

provided the original work is properly cited.

*Radiolabelled Nanoparticles for Brain Targeting DOI: http://dx.doi.org/10.5772/intechopen.92668*

diagnosis of gliomas and will in the course of time certainly facilitate improved therapeutic management of the patients suffering from these tumors. The paradigm shift is IDH mutation as a marker in diffuse glioma classification and reclassification of glioblastoma. Novel drug delivery approaches have substantially influenced the glioblastoma treatment. There is urgent requirement of smart delivery systems for future therapies targeted to specific cells, dependent on intracellular delivery of agents impermeable to BBB. Polymer implants, convection enhanced delivery and degradable nanoparticles are some of the platform technologies for design of novel methods for treatment of glioblastoma. One strategy to optimize the efficacy of molecularly targeted radionuclide agents is to develop nanoparticle-based targeted delivery systems. An abundance of receptors at the surface of the BBB can be utilized by nanoparticles for enhanced brain uptake by coupling with receptorspecific molecules or analogues. The nanoparticles should be designed to bypass efflux transport systems present at the luminal side (such as MDR1). Instead, nanoparticles could be substrates of transport mechanisms enhancing the passage of specific molecules like GLUT-1, IGF-1, and IGF-2 across the BBB. Radiolabelled nanoparticles seem to be novel promising arsenal for potential neurotheranostics.

### *Radiolabelled Nanoparticles for Brain Targeting DOI: http://dx.doi.org/10.5772/intechopen.92668*

*Medical Isotopes*

6 and CED injection at day 12 [31].

longest measured time to progression [32].

bioluminescence live imaging [33].

**7. Conclusion**

survival time of more than 2.5 times that of the control group [29]. Similarly liposomes loaded with beta-negative emitters such rhenium-186 and demonstrated promising results when administered by CED in an orthotopic glioblastoma rat model [30]. Lipid nanocapsules loaded with rhenium-188 in a rat orthotopic model showed a significant survival benefit after intratumoral stereotactic injection at day

A recent approach using radionanoparticles consists of an active targeting approach where the nanoparticles are functionalized and directed against a tumor target. The aim of this active targeting is to optimize the spatial localization of the radioactivity close to the tumor cells. As an example, lipid nanocapsules can be loaded with rhenium-188 and coupled to a monoclonal antibody directed against the CXCR4 antigen. These CXCR4-recognizing immune-nanoparticles irradiate the tumor cells and have been shown to increase efficacy in an orthotopic mouse model. Recurrence for the passive protocol was observed at 65 versus 100 days for the active targeting approach, and this appears to be the most effective therapy with the

**6. Neural stem cells functionalized with radiolabeled nanoparticles**

Neural stem cells (NSCs) are increasingly being used as carriers for targeted delivery of therapeutics to glioblastoma. This requires multimodal dynamic in vivo imaging of NSC in the brain. Such type of technology is in development phase. Cheng et al. reported an innovative strategy for neural stem cell tracking in brain using silica nanoparticles via SPECT [33]. 111In radioisotopes were conjugated to porous silica nanoparticles having large surface area. A series of nanomaterial characterization assays were performed to evaluate the modified mesoporous silica nanoparticles. Loading efficiency and viability of NSCs with 111In-MSN complex was validated. Radiolabeled NSCs were administered to glioma-bearing mice via intracranial or systemic injection. SPECT and bioluminescence imaging were performed periodically after NSC injection. Histology and immunocytochemistry were performed to endorse the findings. 111In-MSN complexes showed minimal toxicity to NSCs and adequate in vitro and in vivo stability. Phantom studies establish possibility of mesoporous silica nanoparticles for NSC imaging. It was found that decayed 111In-MSN complexes exhibited significant fluorescent profiles in preloaded NSCs, thus validating ex vivo data. In vivo, SPECT images reveal actively migrating NSCs toward glioma xenografts in real time after both intracranial and systemic injection. This is in consonance with findings of histology, confocal microscopy and

An urgent requirement for rapid detection and diagnosis of diseases has led to development of contrast agents and imaging techniques. The present challenge is for fast and complete imaging of tissues and lesion categorization that could be obtained by development of nontoxic contrast agents with longer blood circulation time. Nanotechnology provides apt solution to this problem. Nanoparticle based contrast agents have been employed in most biomedical imaging techniques like MRI, fluorescence imaging, CT, ultrasound, PET and SPECT. However, these imaging techniques have certain limitations. These can be overcome by use of multifunctional nanoplatforms to enhance safety, efficacy and theranostic attributes. The WHO 2016 Classification is a major step forward toward a more precise

**122**

diagnosis of gliomas and will in the course of time certainly facilitate improved therapeutic management of the patients suffering from these tumors. The paradigm shift is IDH mutation as a marker in diffuse glioma classification and reclassification of glioblastoma. Novel drug delivery approaches have substantially influenced the glioblastoma treatment. There is urgent requirement of smart delivery systems for future therapies targeted to specific cells, dependent on intracellular delivery of agents impermeable to BBB. Polymer implants, convection enhanced delivery and degradable nanoparticles are some of the platform technologies for design of novel methods for treatment of glioblastoma. One strategy to optimize the efficacy of molecularly targeted radionuclide agents is to develop nanoparticle-based targeted delivery systems. An abundance of receptors at the surface of the BBB can be utilized by nanoparticles for enhanced brain uptake by coupling with receptorspecific molecules or analogues. The nanoparticles should be designed to bypass efflux transport systems present at the luminal side (such as MDR1). Instead, nanoparticles could be substrates of transport mechanisms enhancing the passage of specific molecules like GLUT-1, IGF-1, and IGF-2 across the BBB. Radiolabelled nanoparticles seem to be novel promising arsenal for potential neurotheranostics.
