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Cu-61 production and purification
Abstracts / Nuclear Medicine and Biology 37 (2010) 677–726 −
With 6.90 days half-life the low energy β emitter Tb is very similar to 177 Lu. It emits only a few photons useful for visualization by means of gamma camera. In contrast, 161Tb emits a significant amount of conversion and auger electrons with energies between 3 and 50 keV which contribute 27% of the beta energy but provide much higher local dose density due to their shorter range in tissue (0.5–30 μm). Here, the crossfire effect of beta particles can be enhanced by additionally emitted low energy electrons and greater therapeutic effects of 161Tb-radiopharmaceuticals can be expected. 161 Tb was produced as no-carrier-added by neutron irradiation of massive 160 Gd targets via indirect nuclear reaction 160Gd(n,γ)161Gd→161Tb. The separation by means of cation-exchange chromatography was developed and applied for production of up to 15 GBq of 161Tb with a specific activity of about 85 Ci/mg. 161Tb was successfully used in radiolabelling reactions with DOTA-Tyr3-octreotate. The radiolabelling efficiency and tracer stability was compared with commercially available n.c.a. 177Lu, confirming applicability of 161Tb with already established radiolabelling strategies. 161
719
columns was applied which allows recycling of the target material for uncomplicated electro deposition for the next irradiation cycle. The abandonment of heating and drying steps, applying pumps or any pressure to the columns makes this process suitable for remote handling in hot cells and causing fewer sources of contaminants and enables good/reasonable yields. An overview of the key data (yield at EOB and after processing, specific activity and radiochemical purity) will be presented. doi:10.1016/j.nucmedbio.2010.04.049 Multifunctional radionanomedicine: a new theranostic approach Sabbioni Enricoa, Olivato I a, Bonardi Mauro Lb, Groppi Flaviab, Manenti Simoneb, Manzo Lc a ECSIN, Veneto Nanotech, Rovigo, Italy b Università degli Studi and INFN Milano, Italy c University of Pavia, Italy
doi:10.1016/j.nucmedbio.2010.04.152 Radionuclidic impurities in CNEN-SP
90
90
Sr/ Y generators: Experience at IPEN/
Graciela Barrio, João A. Osso Instituto de Pesquisas Energéticas e Nucleares - IPEN/CNEN-SP Radiosynovectomy has been pursued as an effective alternative to chemical and surgical synovectomy for treatment of arthritis. Because of its favorable physical characteristics, 90Y is used in radiosynovectomy for treatment of rheumatoid arthritis. It has a half-life of 64.1 h and high energy β− radiation (Emax=2.28 MeV). The major advantage is the availability of 90Y from a 90Sr/90Y generator, since the 28.8-year half-life of 90Sr makes it an attractive generator system for long-term usage. Actually, the Radiopharmacy Department of IPEN/CNEN-SP imports 90Y and distributes in 90Y-HA form for Clinics and Hospitals in Brazil, and a project aiming the preparation of 90Sr/90Y generators by ion exchange is under away. The objective of this study is to compare different techniques for determination of 90Sr impurity in 90Y eluted from home made 90Sr/90Y generators due to the high toxicity of 90Sr that is fixed in bone (limit: 74 kBq/ injection). Four different analytical techniques were employed for the evaluation of 90Sr: (i) Beta scintillation counting (Hydex 300 SL) after complete 90Y decay, (ii) Beta dose calibrator (Capintec CRC-15 beta) for evaluation of 90Y half-life, (iii) ICP-OES (Varian Vista-MPX) for evaluation of Sr and (iv) extraction paper chromatography (EPC) using PC-88A and 8-hidroxiquinoline as Y-complexants. The results obtained from the techniques are being compared and validated. Preliminary results show that both ICP-OES and EPC can give accurate and fast results compared with the traditional techniques. doi:10.1016/j.nucmedbio.2010.04.072 Cu-61 production and purification Stefan Thieme, Martin Walther, Hans-Jürgen Pietzsch, Jörg Steinbach Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, PF 510119, 01314 Dresden, Germany Cu-61 (T1/2=3.32 h, Eβ+=1.22 MeV 60%) is a positron emitter from the set of medically useful copper radioisotopes. Its nuclear properties and ease of production make it suitable for positron emission tomography imaging. The 64Zn (p,α)61Cu reaction with enriched Zn-64 as target material seems to be more convenient for the routine production of Cu-61 than the 61Ni(p,n)61Cu route, due to the higher costs of enriched Ni-61. As reported, the 64Zn(p,α)61Cu reaction delivers adequate yields of Cu-61 in an energy window of 19à10 MeV with low contaminants like Cu-60/62 which occur at higher proton energies. Cu-61 was generated using the 64Zn(p,α)61Cu reaction utilizing 16 MeV. For the purification of Cu-61, a system of cation- and anion-exchange
Theranostic nanomedicine is a new integrated nanotherapheutic system which can diagnose, deliver targeted therapy and monitor the response to therapy. This multifunctional nanoplatform is an emerging highlight in nanomedicine that combines both diagnostic/imaging and therapeutic aspects, with a great potential for effective cancer imaging and therapy. In this context, multifunctional radionanomedicine [radionuclide (incorporated for both imaging and therapy]-encapsulated nanocarriers) finds its place. In particular, multifunctional/theranostic radionanomedicines would be able to deliver the radionuclide in a targeted manner to cancer cells, to improve the efficacy and safety of both cancer imaging and therapy with the help of a cancer-targeting ligand. Moreover, the development of multifunctional/ theranostic radionanomedicine is become a possible state-of-the-art in nanomedicine research. Liposomes, dendrimers, quantum dots, iron oxide, nanomicelles, erflurocarbon and carbon nanotubes are commonly used carriers for the development of radionanomedicines. The radioisotopes used in the radionanomedicines for therapy are α-particle emitters (225Ac, 211At ), β-particle emitters (67Cu, 131I, 186Re, 188Re, 90Y) and Auger electron emitters (125I, 111In). Radioisotopes used for imaging are γ emitters (111In, 99m Tc) and β-particle emitters (64Cu, 18F, 124I, 86Y). The aim of this work is to provide an overview of the current status of multifunctional radionanomedicine, and discuss issues to be addressed before exploiting the clinical benefits of radionanomedicines (radionuclide stability in the nanomedicines, radionuclide leakage from nanomedicines, possible interaction between the drug and radionuclide, nanoparticles toxicity). doi:10.1016/j.nucmedbio.2010.04.189
Session C: Clinical Applications of Radiophramaceuticals Carrying Radiometals Oral Presentations A new tumor pretargeting approach based on a bio-orthogonal chemical reaction Raffaella Rossin, Pascal Renart Verkerk, Sandra M. van den Bosch, Roland C.M. Vulders, Iris Verel, Johan Lub, Marc S. Robillard Philips Research Europe, Eindhoven, The Netherlands We designed a novel pretargeting approach based on the inverse-electrondemand Diels-Alder reaction, employing a trans-cyclooctene (TCO) conjugated mAb and a radiolabeled tetrazine (Fig. 1). CC49-TCO, a TAG72 specific mAb, and DOTA-tetrazine were labeled with 125I and 111In. Stability and reactivity of these species were demonstrated in vitro in phosphate-buffered saline, serum and blood. In vivo pretargeting in LS174T xenografts was assessed by SPECT/CT. In mice treated with CC49-TCO
With 6.90 days half-life the low energy β emitter Tb is very similar to 177 Lu. It emits only a few photons useful for visualization by means of gamma camera. In contrast, 161Tb emits a significant amount of conversion and auger electrons with energies between 3 and 50 keV which contribute 27% of the beta energy but provide much higher local dose density due to their shorter range in tissue (0.5–30 μm). Here, the crossfire effect of beta particles can be enhanced by additionally emitted low energy electrons and greater therapeutic effects of 161Tb-radiopharmaceuticals can be expected. 161 Tb was produced as no-carrier-added by neutron irradiation of massive 160 Gd targets via indirect nuclear reaction 160Gd(n,γ)161Gd→161Tb. The separation by means of cation-exchange chromatography was developed and applied for production of up to 15 GBq of 161Tb with a specific activity of about 85 Ci/mg. 161Tb was successfully used in radiolabelling reactions with DOTA-Tyr3-octreotate. The radiolabelling efficiency and tracer stability was compared with commercially available n.c.a. 177Lu, confirming applicability of 161Tb with already established radiolabelling strategies. 161
719
columns was applied which allows recycling of the target material for uncomplicated electro deposition for the next irradiation cycle. The abandonment of heating and drying steps, applying pumps or any pressure to the columns makes this process suitable for remote handling in hot cells and causing fewer sources of contaminants and enables good/reasonable yields. An overview of the key data (yield at EOB and after processing, specific activity and radiochemical purity) will be presented. doi:10.1016/j.nucmedbio.2010.04.049 Multifunctional radionanomedicine: a new theranostic approach Sabbioni Enricoa, Olivato I a, Bonardi Mauro Lb, Groppi Flaviab, Manenti Simoneb, Manzo Lc a ECSIN, Veneto Nanotech, Rovigo, Italy b Università degli Studi and INFN Milano, Italy c University of Pavia, Italy
doi:10.1016/j.nucmedbio.2010.04.152 Radionuclidic impurities in CNEN-SP
90
90
Sr/ Y generators: Experience at IPEN/
Graciela Barrio, João A. Osso Instituto de Pesquisas Energéticas e Nucleares - IPEN/CNEN-SP Radiosynovectomy has been pursued as an effective alternative to chemical and surgical synovectomy for treatment of arthritis. Because of its favorable physical characteristics, 90Y is used in radiosynovectomy for treatment of rheumatoid arthritis. It has a half-life of 64.1 h and high energy β− radiation (Emax=2.28 MeV). The major advantage is the availability of 90Y from a 90Sr/90Y generator, since the 28.8-year half-life of 90Sr makes it an attractive generator system for long-term usage. Actually, the Radiopharmacy Department of IPEN/CNEN-SP imports 90Y and distributes in 90Y-HA form for Clinics and Hospitals in Brazil, and a project aiming the preparation of 90Sr/90Y generators by ion exchange is under away. The objective of this study is to compare different techniques for determination of 90Sr impurity in 90Y eluted from home made 90Sr/90Y generators due to the high toxicity of 90Sr that is fixed in bone (limit: 74 kBq/ injection). Four different analytical techniques were employed for the evaluation of 90Sr: (i) Beta scintillation counting (Hydex 300 SL) after complete 90Y decay, (ii) Beta dose calibrator (Capintec CRC-15 beta) for evaluation of 90Y half-life, (iii) ICP-OES (Varian Vista-MPX) for evaluation of Sr and (iv) extraction paper chromatography (EPC) using PC-88A and 8-hidroxiquinoline as Y-complexants. The results obtained from the techniques are being compared and validated. Preliminary results show that both ICP-OES and EPC can give accurate and fast results compared with the traditional techniques. doi:10.1016/j.nucmedbio.2010.04.072 Cu-61 production and purification Stefan Thieme, Martin Walther, Hans-Jürgen Pietzsch, Jörg Steinbach Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, PF 510119, 01314 Dresden, Germany Cu-61 (T1/2=3.32 h, Eβ+=1.22 MeV 60%) is a positron emitter from the set of medically useful copper radioisotopes. Its nuclear properties and ease of production make it suitable for positron emission tomography imaging. The 64Zn (p,α)61Cu reaction with enriched Zn-64 as target material seems to be more convenient for the routine production of Cu-61 than the 61Ni(p,n)61Cu route, due to the higher costs of enriched Ni-61. As reported, the 64Zn(p,α)61Cu reaction delivers adequate yields of Cu-61 in an energy window of 19à10 MeV with low contaminants like Cu-60/62 which occur at higher proton energies. Cu-61 was generated using the 64Zn(p,α)61Cu reaction utilizing 16 MeV. For the purification of Cu-61, a system of cation- and anion-exchange
Theranostic nanomedicine is a new integrated nanotherapheutic system which can diagnose, deliver targeted therapy and monitor the response to therapy. This multifunctional nanoplatform is an emerging highlight in nanomedicine that combines both diagnostic/imaging and therapeutic aspects, with a great potential for effective cancer imaging and therapy. In this context, multifunctional radionanomedicine [radionuclide (incorporated for both imaging and therapy]-encapsulated nanocarriers) finds its place. In particular, multifunctional/theranostic radionanomedicines would be able to deliver the radionuclide in a targeted manner to cancer cells, to improve the efficacy and safety of both cancer imaging and therapy with the help of a cancer-targeting ligand. Moreover, the development of multifunctional/ theranostic radionanomedicine is become a possible state-of-the-art in nanomedicine research. Liposomes, dendrimers, quantum dots, iron oxide, nanomicelles, erflurocarbon and carbon nanotubes are commonly used carriers for the development of radionanomedicines. The radioisotopes used in the radionanomedicines for therapy are α-particle emitters (225Ac, 211At ), β-particle emitters (67Cu, 131I, 186Re, 188Re, 90Y) and Auger electron emitters (125I, 111In). Radioisotopes used for imaging are γ emitters (111In, 99m Tc) and β-particle emitters (64Cu, 18F, 124I, 86Y). The aim of this work is to provide an overview of the current status of multifunctional radionanomedicine, and discuss issues to be addressed before exploiting the clinical benefits of radionanomedicines (radionuclide stability in the nanomedicines, radionuclide leakage from nanomedicines, possible interaction between the drug and radionuclide, nanoparticles toxicity). doi:10.1016/j.nucmedbio.2010.04.189
Session C: Clinical Applications of Radiophramaceuticals Carrying Radiometals Oral Presentations A new tumor pretargeting approach based on a bio-orthogonal chemical reaction Raffaella Rossin, Pascal Renart Verkerk, Sandra M. van den Bosch, Roland C.M. Vulders, Iris Verel, Johan Lub, Marc S. Robillard Philips Research Europe, Eindhoven, The Netherlands We designed a novel pretargeting approach based on the inverse-electrondemand Diels-Alder reaction, employing a trans-cyclooctene (TCO) conjugated mAb and a radiolabeled tetrazine (Fig. 1). CC49-TCO, a TAG72 specific mAb, and DOTA-tetrazine were labeled with 125I and 111In. Stability and reactivity of these species were demonstrated in vitro in phosphate-buffered saline, serum and blood. In vivo pretargeting in LS174T xenografts was assessed by SPECT/CT. In mice treated with CC49-TCO