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Nano Amplified Therapy. INFN-Milano, INFN-Torino, INFN-Pisa, INFN-Roma3 , CNR-Pisa, University of Torino -Biotechnology Department. Rational :.
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NanoAmplifiedTherapy INFN-Milano, INFN-Torino, INFN-Pisa, INFN-Roma3, CNR-Pisa, University of Torino -Biotechnology Department
Rational: • Hadrontherapy and Radiotherapy are well known and widely used methods to treat cancer when surgery is not suitable or as a complement to a surgical treatment. • The investigation of the use of nanoparticles to increase the average Z and therefore the interaction cross sections has already started. • Use of nanoparticles bound to FDG: no literature is available on a combined use of this approach: nanoparticles bound to FDG (glucose), when injected, should accumulate in the tumour volume at a rate higher than in other cells. • The purpose of the present proposal is to investigate the feasibility and the in-vitro net effect of the proposed approach, called nano-amplified therapy. • 2 years project
1° year • Nano-particles production • Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. For this project 18FDG-AuNPs and Glucose-AuNP (Glu-AuNPs) will be synthetized by University of Torino – Biotechnology Department
1° year • Nano-particles distribution and uptake • The first milestone is the evaluation of the differences in the distribution of FDG with respect to Au-FDG. It is a critical measurement, as it will allow to measure to what extent binding Au nanoparticles to FDG changes the radiotracer distribution and the uptake time. • In order to quantify the comparison, measurements with PET/CT on small animals will be carried out in collaborationbetween Torino and Pisa
1° year PET/CT-basedassesment on Small Animals The uptale of FDG inside differenttissuesshould be modeled with a compartment model estimating the influx and retentioncostant of FDG and FDG/Auseparately. Alternatively a simpleStandardizedUptake Value calculationcould be carried out to estimate the metabolic rate. Co-registered micro-CT and micro-PET images willallow the accurate localizzation of the nano-FDG distribution and willpermit to study the differences, ifany, respect to FDG case and the averagedtumor/normaltissuesratios. The micro-PET/CT scanwill be analyzed and the search for high uptakeregionswill be performed by means of SupportVector Machine and Virtual Antcolonies
IF THESE 1° YEAR MEASUREMENTS WILL BE SUCCESSFULL WE WILL PROCEED WITH THE NEXT YEAR
2° year • In-vitro beam test • Cultured human tumor cells will be used. The glioblastoma U373 and LN229 cell lines and the Non Small Cell Lung Cancer A549 line are already available at INFN-Milano (Radiobiology Laboratory. • All these cell lines are derived from tumors that, due to their resistance to conventional therapies, are eligible for multimodal therapies and hadrontherapy. • Dose- survival curves will be measured for cells irradiated with protons, C-ions and, for comparison, with 6 MeV photons. • Irradiations with protons (therapeutic beam) and C-ions (50 keV/um) will be performed at INFN-LNS. The 6 MeV photon beam will be made available by IstitutoTumori, Milano.
2° year • In-vitro beam test • The results will be analyzed following the linear quadratic model of cell survival, in order to determine the alpha and beta parameters. • RBE values for the different conditions will be determined and compared.