Abstract/Video opens by clicking at the talk title.
Abstract/Video opens by clicking at the talk title.
Effects of alpha radiation on poorly differentiated thyroid cancer spheroids targeted using a 213Bi-labeled humanized aGalectin3-Fab (#574)
Francesco De Rose1, Emanuel Peplau2, Christof Seidl1, Frank Bruchertseifer3, Alfred Morgenstern3, Wolfgang A. Weber1, Armando Bartolazzi4, 5, Arne Skerra2, Calogero D’Alessandria1
1 Klinikum rechts der Isar, Technical University of Munich, Nuklearmedizinische Klinik und Poliklinik, München, Germany
Thyroid cancer (TC) incidence is increasing over the last years. Poorly differentiated (PDTC) and anaplastic TC cells are characterized by poor prognosis and limited treatment strategies1,2. Galectin-3 (Gal3) has been proved to be a reliable TC biomarker, due to its restricted expression to thyroid malignancies, and a useful target for immuno-PET diagnostic imaging3. Herein, we aimed to study the therapeutic potential of a new radio-immunotherapy approach based on alpha-emitters using a 213Bi-labeled humanized anti-Gal3 Fab targeting Gal3 and tested on TC microtumors cell spheroids.
A humanized anti-Gal3 Fab fused with a long PAS (Pro, Ala and Ser) chain to tune the plasma half-life was produced via phage display. The Fab was conjugated with CHX-A”-DTPA, labelled with 213Bi and characterized for stability and binding properties. The PDTC cells BcPAP (tested for Gal3 expression via WB and PCR) were cultured as monolayer and tumor spheroids, then incubated 3h at 37°C in presence of increasing or constant activities for dose-depending toxicity and cell surviving tests, respectively. After treatment, fluorescent anti γ-H2AX mAbs were used to visualize alpha-radiation induced DNA damage via fluorescence microscopy and flow cytometry, while cell proliferation was assessed via ELISA test using WTS-1. The growth of spheroids was monitored by confocal microscopy up to 4 weeks.
Functionalization and labelling of the α-radioimmunotracer were optimized obtaining a radiolabelling yield of 85±7%, radiochemical purity >98% and specific activity of 20±4 GBq/µg. High stability was measured in PBS, human serum and 50mM EDTA up to 4h showing low transchelation of 213Bi . Further characterization in vitro on monolayer BcPAP cells indicated a KD in nM range and an immunoreactivity of 37±3%.
Incubation of BcPAP cultured as monolayer and spheroids with 40 µCi/ml for 3h was found to be the optimal conditions for the treatment in dose-depending toxicity tests. Detection of γ-H2AX activation due to DNA damages repair was possible already 1h after treatment and was significant only for treated cells (Figure1). The proliferation of treated cells was reduced to 50% for spheroids and to 6% for monolayer after 7 days. The size of spheroids treated with 213Bi-labeled Fab was decreasing along 2 weeks, while blocked spheroids incubated continued to grow constantly (Figure2).
We demonstrated the potential of a radio-immunotherapeutic approach based on alpha-emitters by targeting Gal3 on TC cancer. In particular, the immunoprobe was effective in treating TC spheroids mimicking microtumors. The obtained results encourage further investigations of α-radioimmunoprobes based on humanized-aGal3-Fab in preclinical in vivo tests before translation in clinical setting.
Fluorescence microscopy shows higher expression of γ-H2AX in BCPAP spheroids after treatment with the 213Bi-labeled anti-Gal3 humanized Fab. The specificity of alpha radiation induced DNA damage is confirmed by absence of γ-H2AX expression in tumor spheroids blocked with an excess of haGal3-Fab.
Keywords: Galectin-3, Thyroid cancer, Spheroids, humanized Fab, Targeted alpha-particle therapy
Image-guided Boron Neutron Capture Therapy: Preliminary results (#541)
Ghadir Kalot1, Amélie Godard2, Simon Coninx3, Ulli Köster4, Ewen Bodio2, Vincent Motto-Ros5, Jean Luc Coll1, Benoit Busser1, 6, Rachel Auzély3, Christine Goze2, Lucie Sancey1
1 Université Grenoble Alpes, Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, La Tronche, France
Boron neutron capture therapy (BNCT) is a targeted form of radiotherapy. It relies on the sufficient and selective 10B accumulation at the tumor site, which is followed by a neutron beam irradiation. This later induces nuclear capture reactions in the 10B-rich tissues leading to their destruction.
Aza-BODIPY, a fluorescent probe for optical imaging in the NIR, was linked to the clinically available 10B-containing-compound, 10B-BSH. The obtained complex was either encapsulated in a biocompatible hyaluronic acid-based nanogel or evaluated as a free compound.
Efficient cell internalization was observed for both formulations. A faster and a deeper penetration was detected for the free compound, in 2D and 3D glioblastoma models respectively. In vivo, both formulations showed a favorable tumoral accumulation due to the enhanced permeability and retention effect.
The use of theranostic formulations is key in defining the neutron exposure protocol. Promising preliminary data regarding the tumor sizes were obtained, highlighting the potential of these novel formulations as BNCT agents. Experiments are ongoing to optimize the chemical formulations and the biological models in order to validate the results.
AcknowledgmentThe Authors acknowledge the following agencies for funding support: FRM ECO201806006861, ANR JCJC “SPID” ANR-16-CE07-0020, Project JCJC “WazaBY” ANR-18-CE18-0012, CNRS # 2015-9205AAO033S04139, MITI for the project BREVET-ISOTOP, France Life Imaging Thera-BODIPY, and the GEFLUC. The Authors acknowledge also the Optical Imaging platform OPTIMAL (Grenoble France) and the elemental imaging company Ablatom (Lyon, France) for technical collaboration.
(A) Biodistribution of the nanogel formulation in a glioblastoma-bearing chicken egg, obtained using optical imaging. (B) Exposure of a glioblastoma-bearing chicken egg to the PF1b neutron beam line at the Institut Laue-Langevin. (C) LIBS elemental imaging of a collected tumor: Boron is presented in green, phosphorus is presented in blue.
Keywords: Theranostic probes, Optical imaging fluorophores, Boron vectorization
Overcoming drug resistance by MRI-guided ultrasound therapy (#434)
Deyssy Patrucco1, Francesca Garello1, Enzo Terreno1
1 Università degli Studi di Torino, Department of Molecular Biotechnology and Health Sciences, Torino, Italy
The ovarian cancer relapse is characterized by multi-drug resistance (MDR), it is a cancer cell mechanism that origins a drug efflux out of the cells by specific transporters situated on the cell membrane . The aim of this study is to investigate the ability of ultrasound to induce the co-internalization of a chemotherapeutic drug (in nucleus) and an MRI contrast agent (CA) (in cytosol) in chemo-resistant cancer cells, in order to induce a therapeutic effect that can be monitored by MRI.
In vitro experiments were performed on drug-resistant and drug-sensitive human cancer cell lines (A2780 wt, A2780 adr, A2780 cis). They were incubated with an MRI contrast agent (Gadoteridol) and a fluorescent drug (Doxorubicin). The cell membrane permeabilization was produced by low intensity US waves generated for 1’ by a 1 MHz transducer (Precision Acoustics). After ultrasound exposure, cells were pelleted and T1w MRI images were acquired at 7 T MRI. T1 values were calculated and the amount of MRI contrast agent internalized was measured relaxometry/ICP-MS. The cell nucleus loading was assessed by confocal microscopy and spectrofluorimetry. The viability and the proliferation rate were tested using the Trypan Blue exclusion assay and the MTT assay.
The doxorubicin resistant cells (A2780 adr) incubated with the drug and a clinically approved MRI contrast agent (CA) and after the insonation they were able to internalize the fluorescent molecule in the nuclei and at the same time CA in the cytosol, as shown in Fig. 1, in contrast to cells not insonated , where doxorubicin is found only in the cytosol. So, the MRI CA could be used as an MRI reporter of the efficiency of the nuclear uptake. Cell proliferation rate and viability after the treatment were significantly reduced by the treatment as shown in Fig. 2 and could be correlated with the T1 contrast enhancement after the Gd complex internalization.
In vitro experiments suggest that the application of low intensity ultrasound to permeabilize the nuclear cell membrane could be an efficient method for overcoming the chemoresistance. Furthermore, MRI-guided ultrasound-based therapy could provide a fundamental tool for the quantification of the drug internalized in the tumour and the prediction of therapeutic efficacy in drug-resistant tumours.
 Vasey, PA 2003, 'Resistance to chemotherapy in advanced ovarian cancer: mechanisms and current strategies' British Journal of Cancer, 89(Suppl 3), S23 – S28, Cancer research UK: Nature Publishing Group
Keywords: MRI, Chemoresistance, Ovarian cancer, Ultrasound therapy
Improving the efficiency of MRI-guided chemotherapy using sonoporation (#38)
Deyssy Patrucco1, Giulia Tarso1, Chiara Furlan1, Francesca Garello1, Giuseppe Ferrauto1, Enzo Terreno1
1 Università degli Studi di Torino, Department of Molecular Biotechnology and Health Sciences, Torino, Italy
Sonoporation (SNP) is a suitable biophysical method to enhance the cell membrane permeability using ultrasound waves (1-3 MHz) . The cellular internalization of bioactive molecules, such as drugs and contrast agents, has great potential for diagnostic and chemotherapeutic purposes. The aim of this study is to assess the performance of SNP in the field of MRI-guided therapies through in vitro and in vivo cell labeling procedures using the clinically approved MRI contrast agent Gadoteridol. The results obtained with SNP will be compared with other, already validated, labeling methods .
SNP was produced by low intensity unfocused pulsed US waves generated by a 1 MHz piezoelectric transducer (Precision Acoustics). In vitro experiments were performed on different tumor cell lines: K562 (myelogenous leukemia cell line), A2780 (human ovarian cancer line), and TS/A (murine breast cancer cell line). They were suspended in a solution containing contrast agent (CA) and/or Propidium Iodide (PI), a not-permeable fluorescent dye here used as drug model. Finally, MRI-guided in vivo evaluation of the ability of CA to behave as an MRI reporter of the model drug was performed at 7 T MRI on K562 model tumor, while the co-internalization of the PI was confirmed by immunofluorescence. The amount of agent internalized was determined by relaxometry/ICP-MS (CA), and spectrofluorimetry (PI).
In terms of in vitro Gd-labeling efficiency, the SNP-based method performed well when compared with electroporation (EP), hypotonic swelling (HS), and pinocytosis. Importantly, the US exposure did not affect cell proliferation and viability, which resulted to be higher than the values reported using EP. The MRI images demonstrate the potential of this approach when compared with pinocytosis. Cell labeling by SNP takes very short time (1'), and the CA is confined in the cytosol, thus enhancing the ability to generate T1 contrast. Furthermore, and differently from HS and pinocytosis, SNP can be successfully applied in vivo. The internalization data reported in Fig. 1 show that CA may act as MRI reporter of the amount of the co-internalized PI, used as drug model. In preliminary in vivo experiments, the T1w images of mice tumor locally insonated immediately after the injection of the CA and PI, showed a contrast enhancement significantly higher than the not sonoporated group (Fig. 2).
The use of low intensity ultrasound to permeabilize the cellular membrane appears to be a fast and efficient method for cell labeling either for in vitro or in vivo applications. The in vivo SNP could be exploited by exposing a lesion (e.g. a tumour) to US after the co-injection of CA and a drug. Then, MRI T1 contrast could report about the internalization of the drug, and, consequently, predict on an individual basis the outcome of the therapy.
This work was supported by Compagnia San Paolo (n° CSTO165439) and by AIRC (IG 2018).
 Lentacker, EI, De Cock, I, Deckers, R, De Smedt , SC, Moonenb CTW 2014, 'Understanding ultrasound induced sonoporation: definitions and underlying mechanisms', Advanced Drug Delivery Review, 72, 49-64, Elsevier
 Di Gregorio, E, Ferrauto, G, Gianolio, E, Aime, S 2013, 'Gd loading by hypotonic swelling: an efficient and safe route for cellular labeling', Contrast Media Mol. Imaging., 8, 475-486 (2013), Wiley Online Library: John Wiley & Sons, Ltd
Keywords: MRI-guided therapy, Ultrasound, Sonoporation, chemotherapy, MRI
In vivo trafficking of the anti-cancer drug [Ga(oxinate) 3] (KP46) studied with gallium-68 PET imaging (#300)
Afnan Darwesh1, Julia Blower1, Joanna Bartnicka1, Fahad Al-salemee1, Michelle Ma1, Philip Blower1
1 King's College London, Department of Imaging, Chemistry & Biology, london, United Kingdom
Tris (8-hydroxyquinolinato) gallium (III), (KP46, [Ga(oxinate)3]) has been investigated in recent years as an orally administered anti-cancer drug.1Despite extensive preclinical and clinical evaluation of its efficacy, its trafficking to tumours and other tissues remains poorly understood. 68Ga is a readily available positron-emitting radionuclide used for positron emission tomography (PET), offering the opportunity to study the in vivo trafficking of KP46 by PET. Here we report findings of 68Ga trafficking in vitro and in vivo in mice after oral and intravenous administration of [68Ga]KP46
KP46 and [68Ga]KP46 were synthesised by literature methods2,3. Binding of [68Ga]KP46 to Apotransferrin and albumin was measured by size exclusion chromatography. In vivo: Mice in groups A, B and C (n = 3) carried A375 human melanoma xenografts. Group A were given intravenous injections of [68Ga]KP46 subjected to PET imaging over 4 h. Groups B and C were orally administered with [68Ga]KP46 or with [68Ga]KP46 combined with KP46 respectively. Mice were allowed to recover for 3 hours before being re-anaesthetised and scanned for 1 h. All groups were sacrificed for organ harvesting at 4h. Octanol extraction and tissue digestion was performed on tissue samples from groups B and C to test the form of [68Ga]KP46 and measure gallium-69 by ICP-MS
[68Ga]KP46 showed no binding to Apotransferrin and minimal binding to human serum albumin (HSA) indicating the stability of [68Ga]KP46. In group A mice, [68Ga]KP46 did not deliver 68Ga to tumour (2.6±0.9 %ID/g) and most activity concentrated in liver (28.4±6.6% ID/g) and heart (16.9±2.1%ID/g). 68Ga acetate, on the other hand, showed tumour accumulation (5.8±2.4 %ID/g) probably by transferrin dependant mechanism. In group B, most activity remained in the large intestine (61.8 ±21.5%ID/g), with minimal trafficking of radioactivity to other tissues. The majority of radioactivity in tissue samples was in a hydrophilic form, i.e. no longer in the form of [68Ga]KP46. Adding therapeutic dose of KP46 to group C showed no trafficking change and most activity remained in the large intestines (56.5±21.4%ID/g). ICP-MS measurement of gallium-69 in tissue samples was consistent with 68Ga trafficking results
After oral administration of [68Ga]KP46 either as tracer or as bulk drug, gallium is not absorbed from the gut and is not delivered to tumour within the timeframe investigated. We suggest that in this short timescale, delivery of gallium to tumour is not a significant component of the mode of action of this drug. Delivery of 8-hydroxyquinoline could be investigated in the future as an alternative hypothesis for its mode of action
AcknowledgmentThis work was supported by Saudi Arabian Cultural Bureau in The UK
 Chitamber, CR 2004, 'Gallium nitrate for the treatment of non-Hodgkin's Lymphoma', Expert Opin. Investig Drugs, 2004, 13, 531-541, USA: Ashley Publications.
 Colley, P, Domingo, JL, Keppler, BK 1996, 'Preclinical toxicology and tissue gallium distribution of a novel antitumour gallium compound: Tris (8-quinolinolato) gallium (III)', Anticancer Res, 16, 687–692, France.
 Yano, Y, Budinger, TF, Ebbe, SN, Mathis, CA, Singh, M, Brennan KM, Moyer, BR 1985, ' Gallium-68 Lipophilic Complexes for Labeling Platelets', J. Nucl. Med., 26, 1429–1437, USA
Keywords: KP46, Tris (8-hydroxyquinolinato) gallium (III), anti-cancer drug
Preclinical investigation of recombinant human Alpha-1-Microglobulin as an organ protective agent during 177Lu-PSMA-617 radionuclide therapy (#383)
Anders Örbom1, Sven-Erik Strand2, Amanda Kristiansson3, Jonas Ahlstedt4, Bo Åkerström3, Oskar Vilhelmsson-Timmermand5
1 Lund University, Department of Clinical Sciences Lund, Oncology and Pathology, Lund, Sweden
177Lu-PSMA-617 is a promising therapy for metastatic castration-resistant prostate cancer, but maximum accepted kidney absorbed dose limits the administered activity. A radioprotective agent reducing the biological effect to the kidney could increase activity and make therapy available for more patients. Alpha-1-microglobulin (A1M) is a small protein found in all tissues of vertebrates. A1M clears biological fluids from heme and free radicals. It was recently found to protect the kidneys during radionuclide therapy against neuroendocrine tumors , without affecting the therapy effect .
75 male BALB/c mice were included in the study, with sub-groups receiving either 0, 50 or 100 MBq of 177Lu-PSMA-617 and either co-injection with recombinant A1M or vehicle. Blood and urine samples from the mice were analyzed, and for some animals kidney function was tested using dynamic 99mTc-MAG3 renal imaging pre, and 3 and 6 months post, treatment. At 6 months, mice were sacrificed and kidney histology analyzed. In a second study, male BALB/c mice with LNCaP tumor xenografts were investigated. One group (n=8) received 177Lu-PSMA-617 (100 MBq) and A1M and one group (n=8) only 177Lu-PSMA-617 (100 MBq). 177Lu-activity in the tumors was imaged by SPECT and the tumor size monitored for 4 weeks.
No significant differences was found between groups in measurements of blood or urine markers of renal function. No significant difference was found between groups in 177Lu-uptake in the tumor at 24 h p.i. or in tumor size change over time. There is currently analysis of 99mTc-MAG3 renal imaging and evaluation of kidney histology. Preliminary results indicate altered renal function in the 177Lu-PSMA-617 (100 MBq) only group.
We will present the methods used for evaluating the organ protective characteristic of A1M in mice treated with 177Lu-PSMA-617 as well as results from kidney function measured by 99mTc-MAG3 scans and histology.
AcknowledgmentWe would like to acknowledge the contributions of Helena Karlsson and Wahed Zedan to this project.
 Kristiansson, A et al. 2019, ‘Protection of Kidney Function with Human Antioxidation Protein α1-Microglobulin in a Mouse 177Lu-DOTATATE Radiation Therapy Model’, Antioxidants & redox signaling, 30, 1746-1759
 Andersson, C, et al. 2019, ‘rA1M is a potential kidney protector in 177Lu-octreotate treatment of neuroendocrine tumors’, Journal of Nuclear Medicine, 60, 1594-1599
Keywords: psma, radionuclide therapy, α1-Microglobulin, prostate cancer, PRRT
Integrin-mediated delivery of ROS generators into tumor cells for targeted cancer therapy (#93)
Beatrice S. Ludwig1, Florian Reichart2, Stefano Tomassi3, Salvatore Di Maro3, Francesco S. Di Leva4, Luciana Marinelli4, Markus Nieberler5, Horst Kessler2, Ute Reuning6, Susanne Kossatz1
1 University Hospital rechts der Isar/Technical University Munich, Department of Nuclear Medicine, Munich, Germany
High levels of reactive oxygen species (ROS) in tumors have been shown to exert anti-tumor activity, leading to the concept of ROS induction as therapeutic strategy. Ferrocene, a sandwich-like organometallic compound generates ROS through a reversible one-electron oxidation via a Fenton-like reaction. While free ferrocene shows unfavorable pharmacokinetics for systemic therapy, its incorporation into a tumor targeting bioactive molecule could enhance its therapeutic activity. As target structure we chose the ανβ6 integrin which is overexpressed in tumors for intratumoral delivery of ferrocene.
Three RGD-based peptidic ferrocene derivatives with different linkers targeting ανβ6 were synthesized following standard peptide chemistry (Fmoc strategy). Integrin specificity and subtype selectivity of these compounds were determined by an ELISA-type solid-phase binding assay. In six cancer cell lines, ανβ6 expression was determined by immunocytochemical staining and by their capacity to bind a Cy5.5-conjugated ανβ6 ligand. The cytotoxic potential of the ferrocene derivatives was assessed in ανβ6+ and in ανβ6- cells via MTT cell proliferation assay (GI50 values and viability). In vivo, the therapeutic potential will be evaluated using an orthotopic patient derived xenotransplantmodel of head and neck cancer. We will monitor treatment response by integrin-PET and survival assessment.
The ανβ6 targeting ligand (Fig. 1A, 1)  was either conjugated by Cy5.5 or coupled to ferrocene carboxylic acid using three strategies: without a linker (2), with a ω-aminohexanoic acid linker (3), or with a polyethylene glycol (PEG) linker (4). By ELISA-type binding assays all three ligands exhibited high affinity to ανβ6 (IC50 1.19 – 9.49 nM) but not to ανβ3 and α5β1 respectively. In cell binding assays, the Cy5.5 conjugate demonstrated selective targeting of ανβ6-expressing cells (Fig. 1B). Consequently, exclusively in ανβ6+ cell lines (HN, BHY), the ferrocene derivatives provoked an up to 70% reduced cell proliferative activity (Fig. 1C). Corresponding GI50 values ranged between 0.6±0.19 and 31±2 µM. The ferrocene derivative encompassing a ω-aminohexanoic acid linker displayed highest anticancer activity and will be further evaluated with respect to its in vivo performance in a head and neck cancer mouse model by ανβ6-PET monitoring and tumor cell survival analysis.
In summary, it can be stated that in vitro the peptidic ferrocene derivatives proved their potential as promising new molecules for targeted cancer therapy. Especially the ανβ6-targeting peptide bearing a ω-aminohexanoic acid linker showed high ανβ6 selectivity and was most effective in tumor cell killing in an ανβ6-dependent manner. Thus, compound 3 will be selected as a lead molecule for future in vivo theranostic studies.
 O.V. Maltsev, U.K. Marelli, T.G. Kapp, F.S. Di Leva, S. Di Maro, M. Nieberler, U. Reuning, M. Schwaiger, E. Novellino, L. Marinelli, H. Kessler, Angew. Chem. Int. Ed., 55 (2016) 1535-1539.
Fig. 1: Design and in vitro evaluation of ανβ6 ligands.
A) Ferrocene ligand design based on . B) Immunocytochemistry of ανβ6 and binding of the ανβ6-Cy5.5 ligand was evaluated by confocal laser scanning microscopy in ανβ6+ oral squamous cell carcinoma cells (HN) and ανβ6- colon carcinoma cells (RKO). C) Cell viability/proliferative activity [determined by MTT-tests in %] of ανβ6+ and ανβ6- cells in the presence (3 h) of the ferrocene-linked ligands 2-4 compared to the effects of the unconjugated compound 1, was monitored over a cell cultivation period of 69 h in complete medium.
Keywords: ferrocene derivatives, integrins, avb6
Au@DTDTPA(Gd) nanoparticles for multimodality imaging and potential image guided-radiotherapy in cancer (#486)
Océane Campion1, Elodie Lelievre2, Maxime Durand4, Alicia Chateau4, Alexandre Berquand5, Gautier Laurent3, Rana Bazzi3, Stéphane Roux3, Sophie Pinel4, Jérôme Devy1
1 University of Reims Champagne Ardenne, UMR CNRS 7369, Reims, France
Multimodality imaging can provide overall structural, functional, and molecular information, offering the prospect of improved diagnostic and therapeutic monitoring abilities. It has already been demonstrated that gold nanoparticles functionalized by gadolinium chelates Au@DTDTPA(Gd) are able to induce in vitro and in vivo positive contrast in MR images .
In vitro, we look at the effect of Au@DTDTPA(Gd) on cell behaviors and properties such as viability, migration (2D and 3D), adhesion capacity (HA adhesion assays) and stiffness (AFM). The efficiency of Au@DTDTPA(Gd) nanoparticles, but this time, functionalized by molecules of cyanine-5 (near-infrared fluorophore) for 3T MRI and optical (Fluorescent Molecular Tomography) imaging in vivo and ex vivo has been studied in a human triple negative breast cancer (MDA-MB-231) xenograft model in mice.
In vitro, it has been shown that these nanoparticles do not have any effect on cellular viability but lead to a 50% decrease in U251 cells migration. (**p<0.01) By looking at one of the essential process of cell migration implementation, it has been shown that cellular adhesion is also significantly increased in Au@DTDTPA(Gd) treated U251 cells. Additional AFM experiments have shown that nanoparticles affect U87 and U251 cells stiffness. Using FMT in vivo, we could measure a preferential accumulation of the nanoparticles within tumors comparable to the use of a commercial probe (AngioSense680TM).
By acting on these in vitro processes associated with tumor progression, Au@DTDTPA(Gd) endocytosis could reinforce radiation therapy effects for glioblastoma, and on a larger scale, any cancer. This assumption is supported by in vivo nanoparticles tumoral accumulation. These results place our nanoparticles as a promising yet perfectible tool meant to be used for image-guided radiotherapy and/or drug carriers for therapeutic applications.
Keywords: gold nanoparticles, MRI, multimodality imaging, cancer therapy