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Modulo 2:

Riferimento a linee guida

SCHEDA N: 18

AUTOVALUTAZIONE PROGRAMMA

3 Nome programma: Medical Physics

3 Responsabile programma

Giuliano Moschini

3 Obiettivi specifici del programma

We do Physics research of Medical interest and employ know-how and instrumentation mainly drawn from Nuclear and Particle Physics. Most projects exploit the facilities of the nearby Legnaro National Laboratories (LNL). Medium and small accelerators, like Tandem (15 MV), CN (7 MV), and AN (2 MV), provide an extended range of ions and energies to suit all the needs of the Medical Physics. Advanced equipment is available to analyze samples such as XRF (X-ray Fluorescence), PIXE (Proton Induced X-ray Emission) and MicroPIXE; to select single ions for radio-biological experiments and to produce neutrons for the Boron Neutron Capture Therapy (BNCT) tests. LNL facilities include two chemical labs for preparations of medical and environmental samples. A Nuclear Medicine program is carried out at the �Laboratory of Radioisotope and Radiopharmaceutical Studies� (LRRS), part of the Department of Pharmacology and Anesthesiology of the University of Padova and located again at LNL. The LRRS is fully authorized to a Nuclear Medicine practice and accordingly radio-protected. The proximity to the Agricultural and Veterinary Faculties (Agripolis) promotes cooperation on subjects of common interest and exchange of instrumentation and methodology, including the in-vivo experimentation. Finally, collaborations with national and foreign institutes offer further instrumentation and expertise for a wide range of scientific projects. In particular, the partnership with groups of the Padova�s Medical School is intense and continuative. We pursue six research lines, described in the following. Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy Nuclear medicine is a field of medical practice that involves oral or intravenous administration of radioactive materials for use in diagnostics and therapy. Most of radiopharmaceuticals available (95%) are used in diagnostics. These allow the determination of organ�s function, shape, or position or other clinical information from an image of the radioactivity distribution in the body. After administration, the radiopharmaceutical localizes in organs and tissues according to its biological or physiological properties. The gamma radiation from the radiopharmaceutical is externally detected and imaged through a device known as Gamma Camera (or Anger Camera). Two are the main goals of this research line A) We plan to study and develop innovative gamma detectors with sub-millimeter spatial resolution, to inspect structures in organs of small animals inoculated with gamma emitting radio-pharmaceuticals. We want to obtain morphological and especially functional information on organs and systems.

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A radiation emitting drug may also have a therapeutic impact, if able to selectively target tumor cells. To this purpose, one should select radio-nuclides capable of emitting, beside gammas used for imaging, beta or alpha radiations adequate to attacking tumor cells. We have employed the 188Re, featuring two main emissions: a beta component (85%) well suited for radiotherapy and a gamma component (15%) for scintigraphy. One can obtain the Rhenium-188 by simply purchasing a commercial generator 188W/188R that has a few months lifetime. The 188Re-labeling of bio-molecules may often follow the path already studied for Technetium, due to similar chemical properties, and so one can easily produce a similar bio-distribution. Moreover, one may exploit the same detector that is used for Tc, since Re emits gammas of similar energy. We currently employ 99Tc radio-pharmaceuticals during the tuning of the diagnostic, and 188Re radio-pharmaceutical in radiotherapy. B) We also plan to assess the effectiveness of some radio-pharmaceuticals to attack cancer and, generally, their radiation damage, by imaging their bio-distribution. In particular, we propose to study, employing a pre-clinic experimental model, the conjugate 188Rhenium-Hyaluronic acid (188Re-HA) and its therapeutic effectiveness on cancer that is located exclusively or preferentially in liver. This approach relies upon several results we already obtained, pointing out the HA or HA conjugates do nearly exclusively concentrate in liver after intravenous inoculation. This may suggest a true local-regional treatment, to be carried out with no risky and costly surgery, and moreover with high therapeutic effectiveness and no side effects. Early results show a dose-answer effect as for the tumor growing suppression, suggesting that this approach may be employed in vivo. Research Line 2. Trace elements in Biology and Medicine Living tissues carry all natural elements, while mostly in negligible quantity. Some elements, such as Aluminum, Iron, Copper, Zinc, Selenium, Cadmium, etc, present in trace, with a concentration of even less than 1 ppm, are significant because either they are essential to physiological processes, or may become toxic and even give rise to cancer. To measure them, one has to employ highly sensitive techniques. At LNL, we employ several analytical techniques like PIXE, XRF, PIGE, etc., which often outdo traditional analytical chemistry as for sensitivity and offer a nondestructive analysis of a matrix. A microbeam facility is also available, which employs a high intensity, micrometric proton beam to locally inspect a sample and produce maps of its elemental distribution. A chemical laboratory, especially committed to sample preparation, is a key point for a reliable measurement with no contamination, given the extremely low concentration of the elements one wants to measure. We have carried out several research programs addressing medical matters in collaboration with national and foreigner Universities and Institutes, and in particular with groups of the Padova�s Medical School. We have studied elements like Se, Cu, Zn and their role in enzymes operation and cancer development. We have also carried out environmental measures to assess how the intake of these elements, through nutrition and breathing, is correlated with pollutants. Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) The construction of a first phase (FI) of the SPES (Study and Production of Exotic nuclear Species) facility at LNL (Laboratori Nazionali di Legnaro) for the production of intense radioactive ion beams, has been recently approved by the INFN board. The

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SPES-FI facility corresponds to the first part of the driver linac, the RFQ, equipped with a neutron source (through (p,n) reaction on a Be target). This facility will be devoted to interdisciplinary applications, the most important of which will be the BNCT (Boron Neutron Capture Theraphy). The neutron source spectrum provided will be slowed down to the thermal energy range by a proper spectrum shifter device, in order to supply, at the irradiation beam port, a thermal neutron flux level at least of 109cm-2s-1 requested for patient treatment in BNCT applications. The LNL-BNCT facility is foreseen to explore the treatment of extended skin melanoma with such a therapeutic modality. An interdisciplinary research group has been gathered around BNCT project, formed by physicians, biologists, physicists, nuclear engineers belonging to different institutions (like IOV, Istituto Oncologico Veneto, Padova University, Milan Polytechnic, Molteni Pharmaceuticals, ENEA, INFN) aimed at the experimental program of an advanced radiotherapy application of skin melanoma treatment, through the combined application of two irradiation modalities, namely photodynamic therapy (PDT) and BNCT. The main items of the research program are being mainly focused on the neutron irradiation facility design, the development of a new boron carrier suitable both for PDT and BNCT and a new, on-line, biological dose monitoring in both tumor and healthy tissues. Research Line 4. Track-nanodosimetry Ionization events in nanometric biological targets, like DNA or chromatin fibre segments, are believed to have the main relevance for the occurrence of primary lesions, which will turn further on into the observable biological effect. From the point of view of these sub-cellular targets, the ionisation event trail due to a particle crossing is very large, extending to impact parameters much bigger than the target size. Therefore, the number of ionisation events that the biological structure experiences depends on its distance from the particle track. Besides, such targets are so small that the interactions due to the radiation are very few and it is necessary to consider the stochastics of the number and nature of primary interactions and of secondary processes in order to understand the subsequent biological effects. Track-nanodosimetry has the objective to investigate the stochastic aspect of ionization events in particle tracks, by evaluating the probability Pν(D;d) that exactly the number ν of ionizations is produced in a nanometric target volume of size D positioned at distance d from a particle track. In collaboration with the INFN and with the support of the Euratom in the III and IV EU framework programmes, we have developed a track-nanodosimetric counter, based on single electron detection, that is a gas detector able to measure the distributions of ionization events induced by a charged particle in nanometric volumes of tissue-equivalent matter, positioned at different distances from the track. The counter was used to measure the probability of the formation of ionization clusters by primary 244Cm α-particles at 5.4 MeV in sites equivalent to 20.6 nm and 24.0 nm up to impact parameters d of 70 nm. Research Line 5. Analysis and models of neural degeneration in clinical pathology Cognitive alterations are detectable not only in primary neurodegenerative disorders but also in several systemic disorders such as end-stage liver disease, renal failure, pulmonary failure, cardiovascular disease and diabetes. The detection and quantification of such alterations is important in that they can be considered surrogate outcomes for clinical research. At present, one of the cost-effective tools that can be used to this aim in a clinical setting is the electroencephalogram (EEG),

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which provides information on brain electrogenesis and, therefore, on brain functioning. The EEG signal analysis is usually performed in the frequency domain, as the power spectral density provides a method to assess metabolic encephalopathies of different levels of severity. In a clinical context, however, spectral values are generally computed disregarding an important aspect of a measurement: its accuracy. Accuracy depends on the apparatus and environment noise and on the computation algorithm, where the term algorithm refers both to the mathematical procedure and also to the parameters of signal digitization (i.e. sampling rate, amplitude resolution etc). Therefore the optimization of the EEG data acquisition and analysis is our main research goal. Efforts are also being devoted to a possible description of the EEG activity in terms of complexity and signal to internal noise ratio. As fractal (D1) and correlation (D2) dimension require very large data sets to be computed, a study has been performed to assess the relationship between the EEG sampling rate and the D1, D2 values. EEGs recorded from individuals with Alzheimer�s disease (AD) and healthy controls were analyzed. The serendipitous results showed that the EEG complexity of AD patients reaches and overtakes that of healthy controls at high sampling rate. Spectral and non linear methods for EEG analysis seem also promising in the study of EEG changes induced by Intermittent Photo-stimulation (IPS). IPS is one of the most common methods for the �activation� of the EEG, enhancing focal EEG abnormalities and inducing phenomena such as the light derived responses (PDR) and Spectral Harmonics (SH), which remain still poorly understood. A possible underlying mechanism is the stochastic resonance reproduced by neuro-dynamical non linear models. Research Line 6. High rate scintigraphy with a Xenon gas detector We invent and ameliorate new conception Medical Imaging Systems to be used in a Nuclear Medicine environment, and able to perform real-time clinical analysis in Cardiology and Oncology. We have already developed a novel type of gamma camera based on a Multi-Wire Proportional Chamber (MWPC), with pressurized Xenon, equipped with an advanced, high rate digital electronic read-out system (the �CaRDIS� camera). Compared to crystal cameras which are used today, this type of camera has the ability to image low energy ultra-short life radioisotopes enabling radiation doses absorbed by both patients and medical operators to be significantly reduced, giving the capability to perform successive analyses in a short time interval. At the same time, the CaRDIS camera improves count rates and spatial resolution taking advantage of better-targeted radiation doses. The low counting rate of crystal cameras, on the market today, does not allow dynamic cardiac imaging, where high count rates are required in order to obtain good image quality and accurate measurements. In Oncology the use of the imaging system, due to the extremely short life of the proposed isotope, allows the repetition of the analysis before and after the surgeon�s intervention. The total effective dose received by a patient from a first pass cardiac examination, with MWPC and Tantalum-178 radioisotope, is 1/40 of that received by the patient during an identical examination using a Technetium-99m radioisotope and a crystal camera. Unfortunately, the Tantalum-178 generator has never been delivered to the Consortium and all the clinical tests have been carried on using the Tallium generator already developed in the previous CRAFT project. Equipment was tested at the Niguarda

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Hospital (Milan, Italy)

3 Progetti in corso Research Line 1. Development of nuclear detectors and radiopharmaceuticals for

imaging and therapy Project 1.1: SCINTIRAD (INFN Gruppo V) National Coordinator: Prof. de Notaristefani, U. of Roma-3 and INFN Local Project Leader: Prof. Giuliano Moschini, U. of Padova and INFN-LNL This project employs a new design small gamma camera, equipped with a parallel hole collimator, and a highly segmented yttrium-aluminate perovskite (YAP) scintillator coupled to a position-sensitive photomultiplier (Hamamatsu R2486) that provides high resolution images (about 1 mm) on a field of about 4x4 cm. This setup is used to assess in vivo biodistribution, in mice, of 99Tc-labelled new prototype derivative bio-conjugates, consisting of cytotoxic drugs linked to biocompatible polysaccharides. The ongoing research is offering important clues on possible innovative therapeutic approaches with a special emphasis on loco-regional applications. So, preventive studies based on imaging analysis of new drugs may potentially dictate their therapeutic application in vivo. To enhance the YAP camera information, we are also developing SPECT (Single Photon Emission Computerized Tomography) instrumentation, capable of a tri-dimensional imaging and a bigger field of view. This latter, 10x5 cm2, allows the inspection of slightly larger animals, like rats or other rodents, mostly used in pre-clinic tests. Their size is also compatible with micro-surgery, like heart and kidney transplants, prostate manipulation, intra-portal inoculation, cathetering of femoral artery, etc., offering further important scintigraphic applications. We plan to realize this instrument in collaboration with the CAP Research srl., a spin-off of the University of Padova, benefiting from a national funding (art 11, DM 593/00). The new detector features high resolution position-sensitive photomultipliers (Hamamatsu PSPMT H 9500), a new design 256 channel front-end and acquisition electronics, and a high efficiency and energy resolution LaBr3 detector (50x50 mm2). The collimator is now substantially thicker (40 mm) and capable to stop also the 200 keV gamma emission of Re-188. Finally a micrometric stage allows a circular positioning of the detector around the test animal, in order to have different views of the same organ, avoid superposition of two organs and improve the general signal to noise ratio. Project 1.2. PRIN �BANDO 2005 TITLE: "Labelling studies with Tc-99m e Re-188, quality control and pharmacological aspects of targeting molecules in the diagnosis and therapy tyroid carcinoma derived from follicular epithelium non iodocapting." Responsible of the Unit of Padova: Prof. U. Mazzi. Dep. of Pharmaceutical Sciences, U. of Padova.

The project deals with the production of Tc-99m and Re-188 labelled octreotide derivatives, to certify the best ones for imaging tyroid carcinoma derived from follicular epithelium non iodocapting or to radiotherapy. Medical Physics contributes to the project by means of the YAP cameras. YAP camera is a small camera for gamma ray acquisition, equipped with YAP scintillators, which provides images with high spatial resolution (about 1 mm) in a square of 4x4 cm2 , when equipped with a suitable software for analysing the collected data. By means of

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this camera static and dynamic scintigraphic images will be collected and the pharmacokinetic and biodistribution profiles on healthy and tumour bearing small animals, following administration of the new labelled biomolecules, will be recovered. Pharmacological studies are usually performed by the animal sacrifice and the measurement of the activity percentage in different organs by counting their activity. With the YAP imaging techniques, it is possible to estimate qualitatively and quantitatively the distribution of the activity in vivo. Project 1.3. REGIONE VENETO: RICERCA SANITARIA FINALIZZATA- 2005. AZIENDA ULSS N. 8 ASOLO. Title: Diagnosis and Therapy in Oncology field with Radiopharmaceuticals: New Strategies of Molecular Delivery. Scientific Responsable. prof. U. Mazzi, Dep. of Pharmaceutical Sciences, U. of Padova Survivin has been defined as an universal tumour antigen and represents the fourth most significant transcriptosome expressed in human tumours. Survivin overexpression in cancer compared to normal tissues makes it a potentially attractive target for cancer therapeutics. Over the last few years, Peptide Nucleic Acids (PNA) have proven their powerful usefulness in molecular biology procedures, diagnostic assays and as antisense therapeutics. In this context, radiolabelled PNAs will be studied as potential new specific radiotherapeutics. In particular, this research line plans to exploit the unique properties of the PNA technology together with the peculiar expression of survivin in cancer cells to develop a novel tumour targeting strategy. This approach will pursued by developing 99Tc-labelled and 188Re-labelled survivin-specific PNAs which will be employed in both cancer diagnosis and therapy of survivin-expressing tumours. Project 1.4. REGIONE VENETO- Azione Biotec 2 Title: Biocompatible Polymers for Oncology Diagnosis and as Vectors of Anticancer Drug Development, Biodistribution Analysis and Evaluation of Therapeutic Activity Responsable: Prof. Alberto Amadori, Dep. of Oncology and Surgery Sciences, U. of Padova The projects relates to the general field of tumour radiotherapy, where the high potency of the therapeutic agent (the radionuclide) imposes particular care to the delivery strategy so that maximal radioactivity may be achieved in the target organ, while limiting the exposure to other tissues. The possibility of using 188Re in radiotherapy is relatively new to this field of research. So far, the main limiting factor to its use has been the lack of an efficient chelating agent, such molecule being a key element for the administration of the radionuclide to the patient. Recently, in the framework of the research project new bifunctional chelating agents (BFCA) with high affinity for Rhenium have been developed. These molecules allow further studies for the specific targeting of this promising radionuclide towards its practical use for cancer therapy. Indeed, preliminary results obtained by this project may pave the way towards the use of 188Re for both tumour therapy and imaging. The research line is based on what already developed by other scientists for the site-specific targeting of radionuclides others than 188Re (90Y, 99mTc, 68Ga), by using monoclonal antibodies and the avidin-biotin system. In particular, the specific goal is the targeting of prostate cancer in a translational xenogenic mouse model, where human prostate tumours will be implanted in immunodeficient mice and undergo imaging and radiotherapy with 99Tc-labelled and 188Re-labelled Prostate Specific Membrane Antigen (PSMA)-specific mAb.

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Project 1.6. In collaboration with the firm RGM S.p.A. Title: Evaluation of ElettroLaserDiadermic Efficiency of transdermic Transport of molecules Labelled with Tecnezio-99m Responsible: Dr.ssa Maria Cecilia Giron, Dept.of Pharmacology and Anaesthesiology, University of Padova. Elettroporation is a modern technique which allows a simple administration of drugs or chemical species. It consists in the transient formation of hydrophilic pores in the lipid matrix of the skin when pulse electric fields are applied to it with variable frequency in relationship to the deep which has to be reached from the active principle. The application of a pulsed current allows to open and close the tensioactive skin membrane so that the penetration of substances with therapeutic activity is facilitate. The present study has the aim to evaluate the efficacy of ELD in delivering drugs throughout the skin. With the purpose to demonstrate the effective adsorption induced from the presence of an electric field, the molecules of interest will be labelled with Tc-99m and their pathway from the application site to underskin tissues or in the whole body (when the radiopharmaceutical enters in the systemic circulation) will be imaged in vivo thanks to the use of a YAP Camera. Research Line 2. Trace elements in Biology and Medicine Project 2.1 Microelements in the seminal liquid (in collaboration with the Dep. of Medical and Surgical Sciences of the U. of Padova) Several factors, like ions and micro-elements, regulate spermatozoa operation and motility. Many authors have studied the exposure to metals such as cadmium, copper, zinc, and selenium. Cadmium is associated with a decrease of spermatozoa size. Reproductive parameters are correlated to blood content of lead and/or copper, zinc, and selenium. Selenium deficient animals featured low sperm production and poor sperm quality, including impaired motility. Selenium enzymes are in addition linked to the family of glutathione peroxidases. Many infertile humans show a marked decrease of polymerized GPX4 in their sperm. Trace elements in isolated spermatozoa and semen plasma are being measured at LNL by the PIXE method. We are considering the following elements: Na, K, Ca, P, Cl, Al, Cd, Cu and Se. Project 2.3. PIXE micro-beam in localizing metals released from dental and orthopedic implants (In collaboration with the Dental School of the U. of Padova) The release of metals and other elements from dental and orthopedic implants into tissues has been matter of numerous studies. PIXE microbeam is a powerful tool to image the diffusion gradient of such elements in the region of interest, well distinguishing real release from experimental contaminants. We have considered dental implants and rabbit bones sections, and materials such as commercially pure titanium, Ti-6Al-4V alloy and 316 LWM surgical steel. The alloys consisting of Ti, Cr and Ni do actually diffuse slightly in tissues, although much less than Aluminum. This conclusion supports other recent studies claiming Ti diffusion in trace and suggesting the development of more compatible and chemically stable implant coatings, such as calcium phosphates and bio-glasses, to reduce the metals release. In the last decades, many studies have tried to assess if amalgam fillings release mercury. To address this issue with a new method, we have analyzed the mercury

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content of the saliva of patients who underwent amalgam restorations. We have employed the TXRF (Total Reflection X-Ray Fluorescence) technique, capable of sensitivity higher than that of usual analytical techniques. Project 2.4 Environmental and nutritional studies (In collaboration with Agricultural and Veterinary Faculties of the U. of Padova) The �forest decline� occurrence in the regional reserve �Forest of Mesola� has been subject of several research projects for many years. Our group has evaluated the impact of pollutants on the decline of the oak trees, by inspecting the elemental content of their roots. The Fe/Ca ratio Vs the Zn/Ca ratio has been obtained for different classes of declining trees, indicating the role of these elements. We employed the EDXRF (energy dispersive X-ray fluorescence) setup of the Department of Interdisciplinary Physics at LNL. As part of a program of food safety and related human health risk, we have analyzed the elemental content of fish coming from the North Adriatic Sea. We have demonstrated bio-magnification and accumulation effects for some toxic elements, such as Hg, Ni, As, Cd, Pd, Cr. The selenium serum content plays an important role in the disease resistance in ruminants. It has been proved that Se deficiency may cause muscular dystrophy, cardio-myopathy and even death. The purpose of this study was to assess the Se serum content in 2-month-old sucking calves and the correlation with the dietary intake of this element. The samples were measured with the TXRF (Total Reflection X-Ray Fluorescence) setup at the ITAL STRUCTURES Research Laboratory in Riva del Garda (TN). Project 2.5. PIXE elemental analysis on Nigeria mineral talc for Pharmaceutical applications.(In collaboration with the U. of Obafemi Awolowo and the Dep. Of Mineralogy of the U. of Padova) Talc is a versatile industrial mineral that finds application in several areas including the use as pharmaceutical excipients. We have analyzed talc of several deposits of the 800 km long schist belt of Nigeria, to assess if they are of pharmaceutical grade according to British Pharmacopoeia standards. PIXE elemental analysis of these samples have shown that some of Nigeria talc deposits do contain toxic elements, such as mercury, while others are adequate for using in talc industry. This project provides baseline data for talc mine prospecting and exploration in Nigeria and offers a significant contribution to the economic development of this country Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) Project 3.1: Development on the new TEPCs for dosimetry and beam quality monitoring. Radiation dosimetry is quite complex in BNCT treatment because of co-presence of different radiation components with different biological effectiveness. Living cells experience in fact radiation events with a large LET spreading, ranging from few tenth of keV/µm (2.2 MeV gamma rays), to about 300 keV/µm (7Li ions of 870 keV of energy). Moreover, since the neutron spectrum changes with the depth, radiation components relative yield changes with depth in tissue. The radiation field can even change with the time, since the accelerator-based BNCT beam features can not be assumed constant in time. A detailed beam quality monitoring, providing the relative

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contribution of all dose components, has therefore to be taken into account. The total absorbed dose can be divided in the main three components having different biological effectiveness: the gamma dose, the neutron dose and the BNC dose, that means the dose arising from alpha and lithium ions of the 10B(n, α)7Li reaction. Still now, three different detectors are used to assess the three dose components: a gamma detector, a fast neutron detector and a thermal neutron detector. Our aim is having a single detector able to measure contemporary the all three components and their qualities. The experience gained in the last years led us to select the tissue-equivalent proportional counters (TEPC), which have been proved to be able to measure the absorbed dose and its quality with high accuracy both for high energy and low energy neutrons, as well as for fast neutron therapeutic beams and BNCT applications. A first TEPC prototype with an easy tissue equivalent A-150 plastic cathode shells replacement, with different 10B concentration ranging from 0 to 100 ppm, was constructed. Thanks to its large sensitive volume (2.3 cm3), the counter is able to measure in relatively weak radiation fields as those ones available at Legnaro laboratories. Other measurements were performed inside the irradiation cavity of TAPIRO ENEA fast reactor thermal column at very low (20 W) power level. This first TEPC is too large to work in the full-power 5kW TAPIRO radiation field. In order to prevent pile-up event distortions in microdosimetric spectra, a much smaller counter has been designed. The new counter is made of two cylindrical TEPCs (with sensitive volume of 0.6 mm3) with two cathode walls, both of them are of A-150 plastic, however one of them is loaded with 50 ppm of 10B. Having two TEPCs in the same counter satisfies the requirement to get all dosimetric data (gamma dose, neutron dose, BNC dose, plus their quality and the total radiation field quality) just in one measurement. Project 3.2: Optimization of TAPIRO reactor neutron radiation field In vitro and in vivo radiobiological experiments with B16F1 melanotic melanoma cells and C57BL/6 mice bearing a subcutaneous melanoma, aimed to test the potentiality of new boron carriers suitable both for PDT and BNCT, will be performed by the TAPIRO ENEA reactor. TAPIRO is a 5kW fast reactor, able to provide an intense neutron flux inside an irradiation vane. The neutron mean energy is however relatively high and therefore not suitable for the BNC reaction. To study the therapeutic effects of the new boron carriers, it is necessary to build a suitable moderating structure to shift the neutron energy spectrum. The ideal radiation field for BNCT consists of a pure neutron field whose energy is such to become thermal at the tumour location. The foreseen radiobiological experiments will therefore benefit from a pure thermal neutron field. The optimization of the radiation field will be pursued through the use of MCNP4C computer code simulation trials, calculating the thermal neutron flux over the total neutron flux ratio for different moderating structures. The final aim of the project is the construction of an irradiation vane of a few dm3, suitable for cells and small animals (mice) irradiation. Research Line 4. Track-nanodosimetry Project 4.1: Track-nanodosimetric measurements with heavy particles of radiobiological interest.

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To investigate the track structure of heavy particles of radiobiological interest (such as protons and carbon ions), the track-nanodosimetric counter is being installed at one of the beam lines of LNL TANDEM-ALPI ion accelerator (INFN supported experiment STARTRACK: nanodosimetric STructure of hAdRon TRACKs). Track nanodosimetry measurements with accelerated beams give rise to technical problems related to the necessity of reducing the beam intensity as low as about 103 particles mm-2s-1 and to the necessity of reducing to less than 10-5 the probability of cluster pile-up due to multiple events. Therefore, the experiment needs a beam profile detector to visualize very weak beams and a particle rejector detector for recognizing and discarding pile-upped cluster events. We have developed a beam profile detector based on MicroChannel plates to measure the cross sectional image of the accelerated beam, with spatial resolution better than 1 mm, down to beam intensity lower than 103 particle/mm2s-1. First experimental data about the beam-profile detector performances and track nanodosimetry measurements with proton beams are foreseen to be acquired during 2006. Project 4.2: Development of a trigger and particle rejector detector for track-nanodosimetry based on Leak Microstructure The accuracy of STARTRACK experimental data depends on the possibility of rejecting with high efficiency the ionisation events due to more than 1 primary particle. To accomplish this task, an efficient particle detection system made of a trigger and a rejector is necessary. As the simulation of nanometric sites is performed working at very low gas pressure (a few mbar), the trigger and the rejector operate at the same low gas pressure. In order to see if a Leak Microstructure detector (LM) can be used as rejector as well as trigger of STARTRACK, alpha particle detection measurements have been performed at low gas pressure (2-3 mbar) of propane. Experimental data showed that the LM detector works in proportional mode down to 2 mbar of propane with high gas gain. The gas gain is high enough to provide, on the mean, a detectable signal when dealing with single electrons due to the passage of low-ionizing charged particles. The project foreseen the design and construction of a detector based on Leak Microstructure with the double function of trigger and particle rejector for the STARTRACK experiment and the evaluation of its detection efficiency of low ionising primary particles. Project 4.3. Evaluation of the response function of the track-nanodosimetric counter (single electron and cluster detection efficiency) The ability of the track-nanodosimetric counter to detect all electrons of an ionization cluster depends not only on its efficiency ε in detecting single electrons but also on the size of the cluster. As the drift time of a single electron fluctuates around a mean value with a typical Gaussian distribution, the probability that two or more electrons will produce overlapping pulses increases with increasing cluster size. The efficiency of the detector in resolving a number of ν (with ν≤ µ) out of µ electrons of the cluster, Eµ(ν), will depend on the separation in time of the electrons reaching the counter detection stage and on the temporal width of single electron pulses. The single electron detection efficiency ε was calculated with a Monte Carlo code by simulation of the electron transport through the counter taking into account an exact description of the electric field inside the counter. The cluster detection efficiency Eµ(ν) has been estimated by using the mean and the standard deviation of the measured single electron drift time distribution and the FWHM of the pulses, assumed to correspond to the resolving time

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of the counter. The project foresee the construction of a new track-nanodosimetric detector which will allow to measure electrons alternatively, either by counting them one by one (single electron mode) or by counting them globally (proportional counter mode). The comparison, in different ionization density track positions, of the mean cluster size measured with the two modality, will allow to assess experimentally the cluster detection efficiency. Project 4.4: Bayesian reconstruction of nanodosimetric cluster distributions at 100% detection efficiency The track-nanodosimetric counter has a non-uniformly distributed detecting efficiency ε lower than 1. Therefore, the nanodosimetric spectra should be properly processed in order to reconstruct the frequency distribution of clusters produced in the irradiated tissue-equivalent gas. To reach this aim we have developed bayesian analysis methods, whose reliability has been tested on ionisation distributions (IDs) obtained by Monte Carlo calculations, simulating different detection efficiency conditions. In the case of uniform efficiency we have shown that Bayesian analysis provides a valid tool for reconstructing the true IDs, well beyond the maximum measured cluster size. In the case of non-uniform detection efficiency, like that of our track-nanodosimetric counter, it is necessary to take into account the impact parameter dependence of the detector mean efficiency and to subdivide the counter sensitive volume in more domains of different efficiency. The project is going on with the optimization of these analysis methods and foresee their application on the future experimental track-nanodosimetric measurements. Research Line 5. Analysis and models of neural degeneration in clinical pathology Project 5.1 Several possibilities for the optimization of spectral analysis have been tested on a large population of patients with different degrees of hepatic encephalopathy, a neuropsychiatric syndrome that complicates severe chronic liver disease. The EEG activity of healthy controls is also under study with the aim to evaluate its medium and long term stability. Stability is a crucial point for the significance of the measurement itself and for the comparison of results obtained in different laboratories. In the field of non linear analysis, for example, the sampling dependence of fractal and correlation dimension of healthy controls versus patients, originally limited to the occipital region, requires a systematic extension to the whole central nervous system (CNS). The explanation of phenomena induced by IPS and mobile phone pulsation, in terms of stochastic resonance, is in progress.

Research Line 6. High rate scintigraphy with a Xenon gas detector Project 6.1. The new CaRDIS detector Even though the front-end electronic of the existing CaRDIS detector has always showed very good performance, the assumption of the digital approach, with position determination without energy analysis of the pulses, was sufficiently showed to be inconsistent. A new proposal, partially funded by PRIN, is founded on a new idea of data acquisition that will provide at the same time hit position and energy deposition information at

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much reduced cost. At the same time we intend to re-launch the cooperation with Radiopharmacy for the development of a proper Tantalum-178 generator.

4.b Risorse personale [professori ordinari, associati, ricercatori e dottorandi, borsisti post dottorato, assegnasti,

personale tecnico-amministrativo] Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy Staff G. Moschini (PO) P. Rossi (PA) M. Laveder (RC) (P. Boccaccio, INFN-LNL) Assegnasti e Post-doc N. Uzunov, borsista-ICTP (from 2003 to 2005) Dottorandi Personale Tecnico M. Bello Research Line 2. Trace elements in Biology and Medicine Staff G. Moschini (PO) P. Rossi (PA) M. De Poli (INFN-LNL) Assegnasti e Post-doc N. Uzunov, borsista-ICTP (from 2003 to 2005) S. O. Olabanji, borsista-ICTP (from 2004 to 2005) Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) Staff G. Tornielli (PA) P. Colautti (INFN-LNL) V. Conte (INFN-LNL) Assegnisti L.De Nardo (from 2001 to 2005) Dottorandi D. Moro (U. of Ferrara, associate INFN-LNL, from 2003-2005) Research Line 4. Track-nanodosimetry Staff

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G. Tornielli (PA) P. Colautti (INFN-LNL) V. Conte (INFN-LNL) Assegnisti L.De Nardo (from 2001 to 2005) Dottorandi D. Moro (U. of Ferrara, associate INFN-LNL, from 2003-2005) Research Line 5. Analysis and models of neural degeneration in clinical pathology Staff Tullio Minelli (PA) (fino al 30.8.2003) Donatella Pascoli (PA) Dottorandi Valentina Nofrate (from 2001 to 2004) Research Line 6. High rate scintigraphy with a Xenon gas detector B. Baibussinov (INFN) S. Centro (PO) D. Gibin (Ric.) A. Guglielmi (INFN) G. Meng (INFN) F. Pieropaolo (INFN) S. Ventura (INFN)

5.b Risorse finanziarie [media quinquennale] [ la somma di finanziamento ordinario d�Ateneo finanziamenti specifici d�ateneo, finanziamenti

specifici da enti di ricerca locali, nazionali e internazionali, finanziamenti da contratti con enti privati.] Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy 2002 � 2005, Experiments Hirespet, Bioret, Scintirad, G.V INFN; 36 k€ 2003, MIUR ex 60%; 2.5 k€ 2004, MIUR ex 60%; 2.0 k€ 2005, PRIN, National project:�Molecular targeting and development of a new approach to radioreceptorial therapy of tyroid carcinoma derived from follicular epithelium non-iodocapting�; 51k€ 2005, REGIONE VENETO: RICERCA SANITARIA FINALIZZATA � 2005; AZIENDA ULSS N.8 ASOLO. 50k€ Funding Source Total 01-05 PRIN 51 k� Ex 60% 4.5 k� ATENEO 0 OTHERS MIUR 0

14

INFN 36 k� REGIONE VENETO 50 k�

Research Line 2. Trace elements in Biology and Medicine 2002-2003 Progetto di Ateneo �Deperimento del bosco: simbiosi micorrizica e inquiamento del suolo�, resp. Prof. L. Montecchio, Agricultural Faculty of the U. of Padova, 40 k�. 2004 PRIN, �Misure sperimentali e rinnovamento del sistema di acquisizione nel canale PIXE dell�acceleratore AN2000 dei Laboratori Nazionali di Legnaro�, resp. Prof. P. Passi, Dental School, U. of Padova Funding Source Total 01-05 PRIN 18 k� Ex 60% 0 k� ATENEO 40 k� OTHERS MIUR 0 INFN 0 REGIONE VENETO 0

Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) 2001, Esperimento Ater. Gruppo V INFN PD: 26ML 2003, Sviluppo di rivelatori miniaturizzati per il monitoraggio microdosimetrico di fasci neutronici per BNCT. Fondi quota ex60% 3.5 k� 2004, Sviluppo di rivelatori miniaturizzati per il monitoraggio microdosimetrico di fasci neutronici per BNCT. Fondi quota ex60% 3.5 k� 2005, Sviluppo di una metodologia innovativa per il trattamento del melanoma cutaneo mediante terapia per cattura neutronica del boro. Progetto di ricerca di ateneo (interarea). Responsabile: G. Jori. Bando 2004. 45 k� Funding Source Total 01-05 PRIN 0 Ex 60% 7.0 k� ATENEO 45.0 k� OTHERS F. MIUR 0 INFN 26 k� REGIONE VENETO 0

Research Line 4. Track-nanodosimetry 2001: Nanodosimetria di traccia con particelle alfa. Progetto giovani ricercatori (nota MURST 1707 del 22.7.1998) Bando 2000. 20 ML 2001: Misure di Nanodosimetria di traccia con un rivelatore di elettroni singoli. Fondi quota ex60% 6 ML 2002: Misure di Nanodosimetria di traccia con un rivelatore di elettroni singoli. Fondi quota ex60% 4 k� 2003: Esperimento Startrack. Gruppo V INFN PD: 18k� 2004: Esperimento Startrack. Gruppo V INFN PD: 15.5k� 2005: Esperimento Startrack. Gruppo V INFN PD: 14.5k� 2005: Sviluppo e test di un collettore di elettroni ad alta efficienza di raccolta per misure di nanodosimetria di traccia in siti di dimensioni pari a 10 nm. Fondi quota ex60% 3.5 k�

15

Funding Source Total 01-05 PRIN 0 Ex 60% 7.5 k� + 6 ML ATENEO 0 MURST-Giovani Ricercatori 20 ML INFN 48.0 k� REGIONE VENETO 0

Research Line 5. Analysis and models of neural degeneration in clinical pathology 2001, Analisi delle alterazioni neuroelettriche in patologie cliniche, MIUR ex60%, (2001) 5ML 2001-2004, �Patologie immunoinfiammatorie e degenerative del sistema nervoso: aspetti patofisiologici e sviluppo diagnostico e terapeutico�- sottoprogetto �Analisi dei segnali neuroelettrici per lo studio delle patologie immuno-infiammatorie e degenerative del sistema nervoso�, progetto MIUR nazionale (art.11, L. 451/1994), società affidataria del progetto: �Research & Innovation, (2001-2004), 50000 euro, al netto di trattenute, di cui 48000 per una borsa di studio. Funding Source Total 01-05 PRIN 0 Ex 60% 5 ML ATENEO 0 MIUR-art.11,L.451/94 50 k� INFN 0 REGIONE VENETO 0

Research Line 6. High rate scintigraphy with a Xenon gas detector Funding Source Total 01-05 PRIN 58 k�

GRAND TOTAL Funding Source Total 01-05 PRIN 127 k� Ex 60% 19 k� + 11 ML ATENEO 85 k� OTHERS F. MIUR 50 k� + 20 ML INFN 100 k� REGIONE VENETO 50 k� TOT 373 k� + 31 ML

7 Rapporti con altri istituti di ricerca a livello locale, nazionale e internazionale 7.a [specificare concretamente quanto indicato sotto collaborazioni istituzionalizzate indicate al

punto 1 della scheda di Dipartimento] Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy

16

INFN, Azienda Ospedaliera Di Padova Research Line 2. Trace elements in Biology and Medicine INFN, Azienda Ospedaliera Di Padova Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) National collaborations: INFN, ENEA, Politecnico di Milano Research Line 4. Track-nanodosimetry INFN Research Line 5. Analysis and models of neural degeneration in clinical pathology CIRMANMEC (Centro Interdipartimentale di Ricerca sulla Modellistica delle Alterazioni Neuropsichiche). Research & Innovation, Research Line 6. High rate scintigraphy with a Xenon gas detector

7.b [Indicare collaborazioni personali non istituzionalizzate ma rilevanti per il programma] Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy -Dep. of Physics of the U. of Bologna and INFN (D. Bollin, G. Navarria) -Dep. of Physics of the U. of Roma-3 and INFN (F. Denotaristefani) -Dep. of Physics of the U. of Roma-3 and INFN (R. Pani) -Dep. of Biology of the U. of Roma-3 (C. Tanzarella) -Dep. of Pharmaceutical Sciences (U.Mazzi, L.Melendez), -Dep. of Pharmacology and Anesthesiology (G.P.Giron, M.C.Giron, C.Ori), -Dep. of Clinical Veterinary Sciences (D.Bernardini, A.Zotti) -Dep. of Oncology and Surgery Sciences (A.Amadori, A.Rosato) -Dep. of Radiotherapy of the �Azienda Ospedaliera� of Padova (G. Sotti) -Dep. of Natural Sciences, Shumen University "K. Preslavsky", Shumen, Bulgaria (Nikolay Uzunov) Research Line 2. Trace elements in Biology and Medicine - Dep. of Medical and Surgical Sciences of the U. of Padova (D. Armanini) - Dental School of the U. of Padova (P. Passi) -Veterinary Faculties of the U. of Padova (D. Bernardini) -Agricultural Faculty of the U. of Padova (L. Montecchio) -Sandia National Laboratories, NM, USA, Dep. �Radiation Solid Interactions and Processing (Barney L. Doyle) -Institute Ruder Boskovic, Zagreb,Croatia (V. Vlakovič) -Univerity of Obafemi Awolowo, Nigeria (S. O. Olabanji) -Dep. of Natural Sciences, Shumen University "K. Preslavsky", Shumen, Bulgaria (Nikolay Uzunov) Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) Physikalisch-Technische Bundesanstalt (PDT), Braunschweig (Germany) Centre Antoine-Lacassagne Biomedical Cyclotron, Nice (France)

17

Swedish Radiation Protection Authority, SSI, Solna (Sweden) College of Physicians and Surgeons of the Columbia University (USA) Fachhochschule Aachen, Abteilung Jülich (Germany) Research Line 4. Track-nanodosimetry Physikalisch-Technische Bundesanstalt (PDT), Braunschweig (Germany) Weizmann Institut of Science (WIS), Rehovot (Israele) Centre de Physique des Plasmas et de leurs applications de Toulouse(CPAT), Toulouse (Francia) Soltan Institute for Nuclear Studies, Otwock/Swierk, Poland University of Ioannina Medical School (Greece) Swedish Radiation Protection Authority, SSI, Solna (Sweden) Research Line 5. Analysis and models of neural degeneration in clinical pathology -Unité pour la Reserche Neurophysiologique du Systeme Nerveux, Université de Louvain, Bruxelles. Belgium -Centre for Hepatology, Department of Medicine, Royal Free & University College Medical School, London, UK -Centro Diurno per l� Alzheimer, Villa Rota Barbieri - IPAB Vicenza Research Line 6. High rate scintigraphy with a Xenon gas detector

9 Altre attività rilevanti per la ricerca, a livello di Programma [organizzazione di seminari e convegni, partecipazione a seminari e convegni, ecc..]

Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy G. Moschini 1. Since 1985, Chairman of the �Advanced Course in Medical Radioprotection� jointly

sponsored by the U. of Padova and INFN that annually gather scholars and graduate students during one week.

2. Founder and Director of the Specialization School in Health Physics of the U. of Padova, since 2004.

3. Member of the Permanent Steering Committee of the 7th International Symposium on Technetium in Chemistry and Nuclear Medicine. Bressanone (Bz) Italy, September 6-9, 2006

Research Line 2. Trace elements in Biology and Medicine 1. BUOSO M C, GALASSINI S, MOSCHINI G., SCAPINELLI R, ZADRO A, CECCATO D,

UZUNOV N, ROSSI P, PASSI P. (2004).Possibilities of PIXE microbeam in localising metals around dental and orthopaedic implants. 9th International Conference on Nuclear Microprobe Technology and Applications - Cavtat, Dubrovnik,. Sept 13-17, 2004. Presentation by N. Uzunov.

2. BUSO GP, GALASSINI S, MOSCHINI G., PASSI P, UZUNOV N., DOYLE B.L., ROSSI P., PROVENCIO P. (2004). PIXE Microbeam analysis of the metallic debris release around endosseous implants. ECAART 8 CONFERENCE PARIS. Sept 20-24, 2004. Presentation by N. Uzunov.

3. S.O. OLABANJI, A.O. IGE, C. MAZZOLI, D. CECCATO, E.O.B. AJAYI, M. DE POLI,

18

MOSCHINI G. (2004). Quantitative elemental analysis of an industrial mineral talc, using accelerator-based analytical technique. ECAART 8 CONFERENCE PARIS. 20 - 24 SETTEMBRE 2004. Presentation by S. O. Olabanji.

4. S.O. OLABANJI, O.A. IGE, C. MAZZOLI, D. CECCATO, J.A. AKINTUNDE, M. DE POLI, MOSCHINI G. (2004). Accelerator-based analytical technique in the evaluation of some Nigeria�s natural minerals: fluorite, tourmaline and topaz. ECAART 8 CONFERENCE PARIS. 20 - 24 SETTEMBRE 2004. Presentation by S. O. Olabanji.

5. BUOSO MC, GALASSINI S, MOSCHINI G., SCAPINELLI R, ZADRO A, PASSI P. (2003). PIXE microbeam localisation of metals around dental and orthopaedic implants. 16th Intern Conf on Ion Beam Analysis, Albuquerque, New Mexico, USA. 29 Giugno - 4 luglio. (pp. 2-41).

6. S. BALZAN, C. BUOSO, D. CECCATO, M. DE POLI, V. GIACCONE, MOSCHINI G., E. NOVELLI, P. PASSI, V. TEPEDINO. (2003). Quantitative evaluation of essential and not essential metals in muscular, hepatic and renal tissue of horse by means of PIXE technique. The 16th International Conference on Ion Beam Analysis - Albuquerque, New Mexico, USA. June 29-July 4, 2003.

Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) 1. S. Agosteo, L. Casoli, V. Cesari, P. Colautti, N.Colonna, V. Conte, G. Curzio, L. De

Nardo, F. d�Errico, G. Donà, C. Fabris, G. Fortuna, G. Gambarini, M. Geronazzo, F. Giuntini, G. Jori, M. Lollo, G. Roncucci, G. Sotti, L. Tecchio, R. Tinti, G. Tornielli (2001). Advances in the INFN-Legnaro BNCT project for skin melanoma.International physical and clinical workshop on BNCT. Candiolo (Torino) 17 February 2001

2. P. Colautti, V. Cesari, V. Conte, L. De Nardo, G. Tornielli (2001). New TEPCs for Radiation Protection and Radiation Therapy. Neutron Spectrometry and Dosimetry: Experimental Techniques and MC Calculations. Workshop held by the Italian Institute of Culture of Stockholm, Sweden, 18-20 October 2001.

3. P. Colautti, V. Cesari, V. Conte, L. De Nardo, G.Tornielli (2001). Monitor microdosimetrici per fasci adronici.II Congresso Nazionale A.I.F.M. (Associazione Italiana di Fisica in Medicina), Brescia 12-16 giugno 2001

4. V. Cesari, P. Colautti, V. Conte, L. De Nardo, G. Tornielli, N.Iborra and P. Chauvel (2002). Microdosimetric Measurements with a Miniaturized TEPC at the Nice proton therapeutic beam. Workshop on Radiation Dosimetry: Basic Technologies, Medical Applications, Environmental Applications, Rome (Italy), February 5-6, 2002.

5. V. Cesari, P. Colautti, V. Conte, J. Esposito, L. De Nardo, G. Tornielli (2002). First microdosimetric measurements with a 10B-loaded TEPC. Workshop on Radiation Dosimetry: Basic Technologies, Medical Applications, Environmental Applications, Rome (Italy), February 5-6, 2002.

6. P. Colautti, V. Cesari, L. De Nardo (2002).Investigation about proton beam quality with mini TEPCs. XXXVI PTCOG meeting. Catania 28-31 May 2002

7. E. Seravalli, V. Conte, P. Colautti, J. Esposito, L. De Nardo, G. Tornielli, G. Rosi (2003). BNCT microdosimetry at the TAPIRO reactor thermal column. Ninth Symposium on Neutron Dosimetry, Delft, The Netherlands 28 September-3 October 2003.

10. L. De Nardo, P.Colautti, D.Moro, V.Conte, G.Tornielli, G.Cuttone (2003). Micro-dosimetric investigation at the therapeutic proton beam facility of CATANA. Ninth Symposium on Neutron Dosimetry, Delft, The Netherlands 28 September-3 October 2003

11. P. Colautti, V. Conte, L. De Nardo, G.Donà, M. Lollo, G. Tornielli (2004). Microdosimetry for BNCT: Instruments and Methods. Workshop on Current trends in Nanodosimetry and track-structure calculations. Stockholm 2-3 December 2004

12. D.Moro, P. Colautti, G. Gualdriniì, M. Masi, V. Conte, L. De Nardo, and G. Tornielli

(2005). Two miniaturized TEPCs in a single detector for BNCT microdosimetry. 14th Symposium on Microdosimetry, Venice, Italy, November 13-18 2005

Research Line 4. Track-nanodosimetry

19

1. L.De Nardo, P.Colautti, W. Y. Baek, B. Grosswendt, A.Alkaa, P.Ségur and G.Tornielli (2001).Track-nanodosimetry of an Alpha Particle. 13th Symposium on Microdosimetry, Stresa, Italy, May 27-June 1 2001

2. L. De Nardo, G. Tornielli, V. Cesari, P. Colautti, V. Conte, W. Y. Baek, B. Grosswendt, A. Alkaa, P. Ségur (2002).Track-nanodosimetry of an alpha particle. Workshop on Radiation Dosimetry: Basic Technologies, Medical Applications, Environmental Applications, Rome (Italy), February 5-6, 2002.

3. L. De Nardo, M. Lesimple, S. Canella, B. Grosswendt (2003). Reconstruction of cluster distributions at 100% detection efficiency for a track-nanodosimetric counter through a Bayesian analysis. Ninth Symposium on Neutron Dosimetry, Delft, The Netherlands 28 September-3 October 2003

4. L. De Nardo, A. Alkaa, C. Khamphan, P. Colautti, V. Conte (2003).Design of a 10 nm electron collector for a track-nanodosimetric counter. Ninth Symposium on Neutron Dosimetry, Delft, The Netherlands 28 September-3 October 2003

5. B. Grosswendt, L. De Nardo, P. Colautti, S. Pszona, V. Conte, G.Tornielli (2003). Experimental equivalent cluster-size distributions in nanometric volumes of liquid water. Ninth Symposium on Neutron Dosimetry, Delft, The Netherlands 28 September-3 October 2003

6. L. De Nardo, S. Canella, B. Grosswendt (2005). Bayesian Reconstruction of nanodosinetric cluster distributions at 100% detection efficiency. 14th Symposium on Microdosimetry, Venice, Italy, November 13-18 2005

7. L. De Nardo, P. Colautti, V. Conte, M. Poggi, S. Canella, M. Lombardi, G. Tornielli (2004). The INFN nanodosimetry experiment STARTRACK: status report. Workshop on Current trends in Nanodosimetry and track-structure calculations. Stockholm 2-3 December 2004

8. L. De Nardo, P. Colautti, B. Grosswendt (2005). Simulation of the measured ionization-cluster distributions of alpha-particles in nanometric volumes of propane. 14th Symposium on Microdosimetry, Venice, Italy, November 13-18 2005

Research Line 5. Analysis and models of neural degeneration in clinical pathology Donatella Pascoli Member of Scientific Committee of CIRMANMEC (from July 2001) Tullio Minelli Member of editorial Board of the Journal �Non Linear Dynamics in Psychology and life sciences�

Research Line 6. High rate scintigraphy with a Xenon gas detector

11 Prodotti della ricerca 11.b [per ogni anno del quinquennio la quantità totale dei prodotti del programma secondo la

tipologia CINECA, indicare anche eventuali prodotti che non rientrano in questa tipologia.] Legenda: J-ISI: papers on international journals with ISI classification J: other journals C: Congress Proceedings IR: Internal Reports B: Books or chapters of a book P: Patents O: Other products

20

Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy

Year J-ISI J C IR B P O 2001 1 2 2002 1 3 2003 1 2004 2 3 2005 1 1 1

Research Line 2. Trace elements in Biology and Medicine

Year J-ISI J C IR B P O 2001 1 5 2002 1 3 2003 6 3 2004 6 1 2005

Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT)

Year J-ISI J C IR B P O 2001 1 3 2002 3 3 2003 1 2004 4 2005 1

Research Line 4. Track-nanodosimetry

Year J-ISI J C IR B P O 2001 3 2002 3 1 1 2003 1 1 2004 3 1 2005 1

Research Line 5. Analysis and models of neural degeneration in clinical pathology

Year J-ISI J C IR B P O 2001 2002 1 2003 1 1 1 2004 2 2005 1 1

Research Line 6. High rate scintigraphy with a Xenon gas detector

Year J-ISI J C IR B P O 2001

21

2002 2003 2004 2005

GRAND TOTAL

Year J-ISI J C IR B P O 2001 2 1 4 10 0 0 0 2002 4 0 4 8 4 0 0 2003 2 1 8 5 0 0 0 2004 13 1 4 5 0 0 0 2005 2 1 0 2 0 1 0 TOT 23 4 20 30 4 1 0

11.c [indicare i prodotti più rappresentativi con un massimo di 5 per l�intero quinquennio] Research Line 1. Development of nuclear detectors and radiopharmaceuticals for imaging and therapy UZUNOV N., BELLO M., BOCCACCIO P., MOSCHINI G., BALDAZZI G., BOLLINI D., DE NOTARISTEFANI F., MAZZI U., RIONDATO M. (2005). Performance measurements of a high-spatial-resolution YAP camera. PHYSICS IN MEDICINE AND BIOLOGY. vol. 50, pp. N11-N21 ISSN: 0031-9155. PATENT REQUEST. �Measurement of the object distance by employing a high spatial resolution scintillating camera�. This request has been submitted to the INFN during year 2005 and approved in the current year (CD 23/02/2006). It is about a method to calculate the distance of the emitting gamma object by only employing a position sensitive detector (scintillating camera), with no detection of object movement (�statically�). This invention may help to localize lymph-nodes during biopsy or ablation. Research Line 2. Trace elements in Biology and Medicine G.P. BUSO, S. GALASSINI, MOSCHINI G., P. PASSI, A. ZADRO, N.M. UZUNOV, B.L. DOYLE, P. ROSSI AND P. PROVENCIO. (2005). PIXE microbeam analysis of the metallic debris release around endosseous implants. NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH. SECTION B, BEAM INTERACTIONS WITH MATERIALS AND ATOMS. vol. 240, pp. 91-94 ISSN: 0168-583X. Research Line 3. Microdosimetry for Boron Neutron Capture Therapy (BNCT) E. Seravalli, V. Conte, P. Colautti, J. Esposito, L. De Nardo, G. Tornielli, G. Rosi BNCT microdosimetry at the TAPIRO reactor thermal column. Radiat. Prot. Dosim. 110: 579-586 (2004) Research Line 4. Track-nanodosimetry L. De Nardo, P. Colautti, V. Conte, W. Y. Baek, B. Grosswendt and G. Tornielli

22

Ionization-cluster distributions of α-particles in nanometric volumes of propane: Measurement and calculation. Radiation and Environmental Biophysics 41:235-256 (2002) Research Line 5. Analysis and models of neural degeneration in clinical pathology F. Ferro Milone, F. Aporti, T.A. Minelli, V. Nofrate, A. Porro and A. Leon Cananzi: EEG patterns in Alzheimer�s disease: intermittent photic stimulation and sampling rate. European Journal of Neurology 10 (s1), 92-93 (2003).