3rd-INCC

Gamma-ray spectroscopic characterization of radioactive preparation for production process validation in a PET cyclotron facility

22 Sept 2011, 17:30

1h 30m

Paladini (Città del Mare, Terrasini - Palermo - Sicily - Italy)

poster Health Physics and Radiation Chemistry Poster Section 2

Speaker

Dr Ignazio Vilardi (Nuclear Medicine Department, Multimedica Scientific Institute, Sesto San Giovanni (MI), Italy)

Description

Introduction The Pharmaceutical Industry in European Community applies very strict rules for quality assurance in production and control of pharmaceuticals. A manufacturer’s authorization guarantees that all authorized pharmaceuticals satisfy the Good Manufacturing Practice (GMP) requirements for medicinal products. Many national Governments have created their own GMP guidelines. In Italy, the supplement of Gazzetta Ufficiale of Italian Republic n° 274 (23 November 2010) states the guidelines to define and to control manufacturing processes, and for inspections in pharmaceutical laboratories. One of the requirements is related to validation: a new process or after significant changes to the facilities, the equipments or the process, which may affect the quality of the product, should be validated. This validation is requested to verify the accuracy of parameters included in the process and the reproducibility. GMP guidelines fixes to 0.1% for 18F and 1% for 11C and 13N the limits of the total radioactivity due to radionuclide impurities present in the pharmaceutical preparation at the administration time. In this study gamma-ray spectroscopic characterization of radioactive preparation from proton bombardment for production process validation of 11C, 13N and 18F are presented. Materials and methods The PET centre at San Raffaele Scientific Institute is equipped with two cyclotrons, IBA Cyclone (18/9 MeV) and CTI Eclipse (11 MeV). 11C is produced with both cyclotrons by 14N(p,n)11C nuclear reaction with Al target and Havar foils (CTI) or Al foils (IBA), respectively. With CTI 12.4±0.2 GBq are produced with a 60 min irradiation at a beam current of 25 microAmpere, while with IBA 59.7±5.3 GBq are produced with a 60 min irradiation at a beam current of 35 microAmpere. 13N is produced with CTI by 16O(p,alpha)13N nuclear reaction with Al target and Ti foils. Produced 0.23±0.01 GBq/ml, with a 20 min irradiation at a beam current of 40 microAmpere. 18F is produced with both cyclotrons by 18O(p,n)18F nuclear reaction: CTI uses Ag/Nb target (dual bombardment) and Havar foils, while IBA uses Nb target and Havar foils, respectively. With CTI 2.1±0.2 GBq/ml are produced with a 60 min irradiation at a beam current of 20 microAmpere, while with IBA 0.7±0.1 GBq/ml are produced with a 10/12 min irradiation at a beam current of 32 microAmpere. Spectroscopic measurements were performed using an High-Purity Germanium detector with 18% relative efficiency and 0.14% energy resolution at 1332 keV. Detector calibrations were performed with 152Eu and 133Ba certified sources. For the detection and quantification of impurities, the preparations were examined, after an adequate time to allow the decay of nuclide to a level that permits the detection of impurities, for at least 24 hours. The measured activity values were normalized at the end of bombardment and to the preparation volume. Results Analysis of produced radioactive preparations showed the presence of impurities: 44Sc, 44mSc, 46Sc, 47Sc, 48V, 52Mn, 56Co for a 13N sample, 52Mn, 54Mn, 56Co, 57Co, 58Co, 67Ga, 109Cd for a 18F-CTI sample and 51Cr, 52Mn, 55Co, 56Co, 57Co, 57Ni, 58Co, 67Ga for a 18F-IBA. No nuclide was detected on 11C sample of both cyclotrons. The 13N sample showed also the presence of 18F, identified with its lifetime. Measured impurities activities ranged from 120 Bq to 700 Bq, resulting in 2.7±0.1•10-6 % for 13N, 6.9±1.5•10-7 % for 18F-CTI and 4.0±1.4•10-6 % for 18F-IBA. The type of radionuclides found in this study are inherent with the targets and foils employed for proton irradiation. In particular Sc is likely obtained from the nuclear reaction Ti(p,x)Sc, 48V from 48Ti(p,n)48V, all Co isotopes from natFe(p,x)Co or natNi(p,x)Co, Mn isotopes from 54Fe(p,x)Mn, 51Cr from 54Fe(n,alpha)51Cr, 57Ni from 58Ni(p,d)57Ni, 67Ga from 67Zn(p,n)67Ga and 109Cd from 109Ag(p,n)109Cd. Conclusion Measured activities of impurities are much less than the fixed limit, therefore the production processes of 11C, 13N and 18F can be considered validated concerning the radionuclide purity. We conclude that our production processes have a high degree of confidence and can permit to detect and correct deviations which could cause problems during nuclide production.