166Ho-microspheres as a promising radiopharmaceutical for therapy

XXVI Congreso Brasileño de Medicina Nuclear 11 de octubre al 14 de octubre de 2012 Salvador de Bahía, Brasil
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INTRODUCTION: Liver cancer is not among the most prevalent cancer in Brazil. However, high technology is required for its proficient diagnosis and treatment. According to the consolidated data on cancer mortality in Brazil, this disease is not in the top ten incidents with incidence rate between 1.07 to 9.34/100,000 for men and 0.28 to 7.04/100,000 for women. Therefore, liver metastases frequently occur during the progression of various solid tumors, especially colorectal cancers with 14/100,000 incidence rate for women and 15/100,000 for men. One type of therapy of this disease can be an alternative radiotherapy mode with the use of radioactive microspheres injection in liver’s artery with a diameter between 20 and 50 μm. The basis for such therapy is that tumors are usually rich in vasculature and that liver metastases are almost exclusively dependent on arterial blood supply. Polymeric and glass compounds is the optimal for preparing microspheres labeled with holmium. The potential use of microspheres labeled with 166Ho combines biocompatibility microspheres and immobilization of 166Ho, which has favorable physical characteristics for image guided radionuclide therapy. The 166Ho decay by beta emission (T1/2=26.8h, Emax=1.84 MeV) for therapeutic purposes and gamma emission (80.6 keV – 6.7%) that can be used for image produce. The 166Ho is produced by exposing suitable target materials containing 166Ho to the neutron flux in a nuclear reactor for an appropriate time to occur the (n,?) reaction. Target purity is important to avoid radionuclidic impurities after irradiation. The possible contaminants of holmium targets are rare earths such as Ytterbium, Lutetium, Lanthanum and Cerium.

MATERIALS AND METHODS: This study used microspheres samples produced by Biotechnology and Science and Technology of Materials Center. The samples were irradiated with a neutron flux in a 1.0x1013 n.cm-2s-1 for 1 hour at the IEA-R1 nuclear reactor. After the irradiation the samples were analyzed by Gamma Spectrometry detector to measure the 166Ho activity and also the level of radionuclidic impurities.

RESULTS AND CONCLUSIONS: The highest specific activities obtained were 21.3 GBq.g-1. Some undesirable contaminants were found in some samples. The radionuclidic impurities levels are altered when different activation times, neutron flux and decay time are applied. This occurs due the different physical properties as cross-section and decay constant. Considering contamination level by each rare earth of 0.1% (w/w of Ho) and 7 days after EOB the maximum of radionuclidic impurities would be in 10-2. Nowadays, the IEA-R1 reactor facilities at IPEN/CNEN-SP are suitable for production of 166Ho microspheres (glass or polymeric). The experimental activation process was performed with low neutron flux and time to test. However, can use higher neutron flux and irradiation time to produce microspheres with therapeutically activities. New studies about the microspheres structural integrity and their stability were started and “in vivo” phase will be after preliminary results and collaboration with other research centers.