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Meeting Report (Pdf) Nanosized Delivery of Radiopharmaceuticals 2nd Research Coordination Meeting of the CRP 5–9 October 2015 Padua, Italy (May (May 13) 1 4 - C FOREWORD The currently used therapeutic agents in nuclear medicine continue to pose medical challenges mainly due to the limited uptake of radiocompound within tumour sites. This limited accumulation accounts for the fact that current beta-emitting therapeutic nuclear medicine agents have failed to deliver optimum therapeutic payloads at tumour sites. Actually, no other radiolabelled therapeutic agent has been capable to get close to the remarkably high target accumulation that was demonstrated by the long-lasting radionuclide I-131 in thyroid cancer. This means that metastases of several different types of aggressive cancers cannot be controlled, making it difficult to treat cancer patients. Therefore, new delivery modalities that result in (i) effective delivery of therapeutic probes with optimum payloads, site specifically at the tumour sites, minimal/tolerable systemic toxicity, and (ii) higher tumour retention, would bring about a clinically measurable shift in the way cancers are diagnosed and treated. Nanotechnology has the potential to bring about this paradigm shift in the early detection and therapy of various forms of human cancers because radioactive nanoparticles of optimum sizes for penetration across tumour cell membranes can be engineered through a myriad of interdisciplinary approaches, involving teams of experts from nuclear medicine, materials sciences, physics, chemistry, tumour biology and oncologists. Therefore, the overall approach which encompasses application of nanoparticulate radioactive probes in combination with polymeric nanomaterials has a realistic potential to generate the next generation of tumour specific theranostic nanoradiopharmaceuticals and minimize/eliminate delivery and tumour accumulation problems associated with the existing traditional nuclear medicine agents. This CRP was formulated based on the conclusions and recommendations of a Consultants Meeting (27−31 May 2013), and is utilizing the knowledge and expertise in synthesizing polymer nanoparticles using radiation technologies developed under the framework of a completed CRP “Nanoscale Radiation Engineering of Advanced Materials for Potential Biomedical Applications”. The first RCM was held on 7–11 July 2014 in Vienna, Austria, where the participants reviewed the relevant work being carried out in their respective institutions, as well as discussed and adopted the work plan for the next period. The meeting report is available at: http://www- naweb.iaea.org/napc/iachem/working_materials/RCM1-F22064_REPORT.pdf. The second RCM was held on 5–9 October 2015 in Padua, Italy. The meeting report from that event is this Working Material. The IAEA wishes to thank all participants for their valuable contributions. The IAEA officer responsible for this publication was Agnes Safrany of the Division of Physical and Chemical Sciences. CONTENTS 1. SUMMARY ...................................................................................................................... 3 1.1. INTRODUCTION .............................................................................................. 3 1.1.1. Remaining Challenges ............................................................................ 3 1.1.2. Role of nanotechnology .......................................................................... 4 1.1.3. Research already in progress in Member States ..................................... 4 1.2. CRP OVERALL OBJECTIVE ........................................................................... 5 1.2.1. Specific Objectives ................................................................................. 5 1.2.2. Expected research outputs ...................................................................... 5 1.3. REVIEW OF THE PROGRESS OF THE WORK IN INDIVIDUAL INSTITUTIONS ............................................................................................... 12 1.3.1. Argentina .............................................................................................. 12 1.3.2. Brazil ..................................................................................................... 12 1.3.3. Egypt ..................................................................................................... 13 1.3.4. Iran ........................................................................................................ 14 1.3.5. Italy (Milan) .......................................................................................... 14 1.3.6. Italy (Padova) ........................................................................................ 15 1.3.7. Italy (Palermo) ...................................................................................... 16 1.3.8. Malaysia ................................................................................................ 16 1.3.9. Mexico .................................................................................................. 17 1.3.10. Pakistan ................................................................................................. 17 1.3.11. Poland ................................................................................................... 17 1.3.12. Poland- POLATOM .............................................................................. 18 1.3.13. Singapore .............................................................................................. 19 1.3.14. Thailand ................................................................................................ 19 1.3.15. United States of America ...................................................................... 20 1.4. 4. CONCLUSIONS AND RECOMMENDATIONS ....................................... 21 2. PREPARATION OF ALBUMIN AND GOLD/ALBUMIN NANO-PARTICLES BY RADIATION-INDUCED CROSS-LINKING ......................................................... 22 M. Grasselli, S. del Valle Alonso, E. Achilli, M. Sir, C. Flores 3. RADIO-INDUCED CROSSLINKING OF ALBUMIN NANOPARTICLES FOR RADIOPHARMACEUTICALS DELIVERY SYSTEM ............................................... 31 A. Benévolo Lugão , G.H.C. Varca; R.G. Queiróz; L. Goulart; A. Geraldes; J.G. Batista; A. Silva; Jessica Leal 4. RADIOSYNTHESIS, QUALITY CONTROL AND BIOLOGICAL STUDIES OF NANOSIZED RESVERATROL-AU-198 ............................................................... 38 T. Hafez, T.M. Sakr, H.A. Abd El-Rehim K.K. Katti, L. Watkinson, T. Carmack, C.J. Smith, C.S. Cutler, K.V. Katti, 5. DEVELOPMENT OF CHITOSAN-BASED NANOPARTICLES FOR MONOCLONAL ANTIBODY RADIOPHARMACEUTICALS DELIVERY ............ 42 S. Shanehsazzadeh, A.R. Jalilian (May (May 13) 1 4 - C 6. RADIOLABELED NANOSIZED DELIVERY SYSTEMS FOR THERANOSTICS OF PRIMARY AND METASTATIC COLORECTAL CANCER ........................................................................................................................ 48 L.Melendez Alafort, A.Rosato G., Pasut, C. Bolzati, S. Mocellin, N.Salverese, D.Carpanese 7. CANCER-FIGHTING DIAGNOSTIC AND THERAPEUTIC NANOGELS .............. 59 C.Dispenza, M.A. Sabatino, N. Grimaldi, L. Ditta, E. Murugan, M. Jonsson 8. NANOSIZED DELIVERY SYSTEMS FOR RADIOPHARMACEUTICALS ............ 72 S.N.M. Janib 9. NANOSIZED DELIVERY SYSTEMS FOR RADIOPHARMACEUTICALS: NANOSIZED RADIOLABELED POLYAMIDOAMINE DENDRIMERS FOR TUMOR IMAGING AND TARGETED THERAPY .................................................... 78 B.E. Ocampo-García, G. Ferro-Flores, F.D.E.M. Ramírez De La Cruz, C.L. Santos-Cuevas, E.P. Azorín- Vega, E. Orocio-Rodríguez 10. NANOSIZED DELIVERY SYSTEMS FOR RADIOPHARMACEUTICALS ............ 89 I.U. Khan, R. Zahoor, A. Shahid, F. Iram1, 11. NANOSIZED DELIVERY SYSTEMS BASED RADIOPHARMACEUTICALS IN POLAND ................................................................................................................... 99 M. Maurin 12. POLYMER-BASED NANOCARRIERS FOR RADIOPHARMACEUTICALS ....... 107 P.Ulanski 13. DEVELOPING DELIVERY SYSTEMS FOR RADIOPHARMACEUTICALS........ 130 S.C.J. Loo 14. GREEN SYNTHESIS OF POLYSACCHARIDE AND POLYPEPTIDE-BASED NANOPARTICLE TOWARD THE CREATION OF STABLE AND FUNCTIONALIZED RADIOPHARMACEUTICS FOR DIAGNOSIS AND THERAPY .................................................................................................................... 139 W. Pasanphan, T. Rattanawongwiboon, S.Wongkrongsak, T. Tangthong 15. IN VIVO STUDIES AND PRODUCTION OF NANOSIZED DELIVERY SYSTEMS FOR RADIOPHARMACEUTICALS ....................................................... 153 K.V. Katti 1 2 1. SUMMARY 1.1. INTRODUCTION Nuclear medicine is an important medical specialty involving the application of radioactive substances in the diagnosis and treatment of diseases. There are a number of diagnostic and therapeutic radiopharmaceuticals that are FDA approved for use in human patients. These radiopharmaceuticals, once administered to the patient, can localize to specific organs or cellular receptors. This property of radiopharmaceuticals allows nuclear medicine the ability to image the extent of a disease process in the body, based on the cellular function and physiology, rather than relying on physical changes in the tissue anatomy. Nuclear medicine has the ability to identify medical problems at an earlier stage than other diagnostic tests. Nuclear medicine is often compared to "radiology done inside out", or "endo-radiology", because it records radiation emitting from within the body rather than radiation that is generated by
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