Samenvatting
During the last decades the use and development of nuclear medicine practices for diagnosis and therapy have been increasing steadily. This is partly due to the advent of more efficient and dedicated accelerators that allow for production of larger activities of those radionuclides that have already an established status but also to the possibility that high power beams offer for development of promising new radionuclides. Effective use in clinical applications asks for some common characteristics for all radionuclides: non-toxicity at the level of mass quantities injected, high specific activity meaning availability in a no carrier added form, minimal disturbance of the image quality or therapeutic effect by the presence of contaminating radionuclides, safe production conditions respecting local dose rate limits to personnel and availability in sufficient amounts at a reasonable cost. Several of these parameters are determined by a strict control and knowledge of the production conditions of the radioactive material. Hence a systematic study of the pathways and of the optimization of radiochemical procedures are needed to obtain a suitable diagnostic or therapeutic radionuclide. A first need to study possible production routes for radionuclides is the understanding of the fundamental rules governing nuclear reactions induced by charged particles and the significance of threshold and Coulomb barrier. This work hence starts by describing the influence of the stopping and energy degradation by electronic interaction of the bombarding particles on the fact that the probability of the nuclear interaction, expressed by the cross section and excitation function, is not constant throughout the depth of a bombarded target layer. Knowledge of the excitation functions is essential to calculate yields of the desired radionuclide and of the radionuclidic contaminants. VUB cyclotron laboratory has a long tradition of experimental determination of the excitation functions and collaborates with authors and developers of different theoretical codes to validate the excitation functions based on models of the structure of the nucleus and its interactions with accelerated particles. The comparison between experimental and theoretical data are far from excellent. Hence more experimental data are needed to refine and improve the description of the more complex reaction pathways. In the VUB Cyclotron lab excitation functions are determined experimentally through the stacked foil activation technique where target foils of interest are interleaved with monitor foils used to obtain reliable information about beam energy and particle flux. In order to derive these parameters from the measurements a Visual Basic interactive algorithm has been developed. Procedures for accurate energy and photopeak efficiency calibration of HPGe spectrometers are developed. From the measurement of the induced activity in the target foils on calibrated ??spectrometers, the cross sections (and excitation functions) are calculated using analytical formulae. The total yield for thick targets, reducing the exit energy of the incident particles to a value below the threshold, in saturation conditions (YSAT in GBq/µA) is derived in functions of energy depending cross sections and stopping power and target and beam characteristics. All derived formulas are used in the experimental study of bombarding particle-target combinations:- the formation of 114mIn and 117mSn is investigated by measurement of the excitation
functions of alpha induced reactions on enriched 116Cd and 114Cd;
- the excitation functions of proton induced reactions on enriched 64Ni targets for the
production of 64Cu are determined;
- the excitation functions of deuteron induced reactions on natural thallium for the
production of no carrier added 203Pb and possible contaminants.
As these experiments use either enriched isotopes or targets that are made of an element that is not commercially available in foil format, custom preparation of targets is needed. The techniques and conditions used in the electrodeposition of 3 types of targets are discussed. After description of irradiation conditions, methods for activity assessment and data analysis, the results for the cross sections for production of all activation products are discussed.
Comparison with literature values and with the results of the TENDL2010 database built on the a-priori calculation with the code TALYS 1.2 are given.The thick target yields for-production of the medically relevant 117mSn, 64Cu and 203Pb are derived. As it is well known that apart from the radionuclide of interest, other radionuclides of the same element or another element can be produced in the same energy range, it is important to study the possible means to reduce these contaminants. This is done in the second optimization step: the evaluation of the incident particle energy, of the thickness of the target layer, and of the irradiation and decay times. As an example, the optimum parameters for the production of the201Tl radioisotope, widely used in nuclear medicine, are determined. Therefore an Excel Yield&Shield worksheet has been developed. The worksheet makes use of the discrete data for the excitation functions and for the stopping power of the thallium target material which are approximated by continuous functions: a polynomial (or a set of polynomials) for the cross section and a sum of three exponential decay terms for the stopping power. When both approximations are used in an Excel sheet with stepwise increase of thickness of the target layer as argument, a set of discrete points of the saturation curve is obtained. The best fit for each of the resulting saturation curves proves to be a Gompertz function. This method of approximation combined with a powerful Visual Basic macro, based on Divide et Impera and binary search method, gives as output the optimum irradiation parameters in less than 100 iteration, so it can be run on any standard personal computer. The production parameters were evaluated taking the European Pharmacopoeia's requirements regarding radionuclidic impurity as boundary conditions. The developed algorithm has been adapted for the production of other medical important radionuclides i.e. 67Ga and 111In. At the same time the optimum thickness of the lead shield of the processing hotcells resulting in an outside gamma dose rate during the separation chemistries that meets the locally accepted dose rate level for a controlled area, has been calculated. For that an optimization algorithm based on binary search method has been developed. The algorithm makes use of the gamma dose rate per unit of flux, the Taylor build-up coefficients and the attenuation coefficient of lead approximated by appropriate functions. The algorithm outputs the required thickness of the lead shield of the processing hotcell and the half value layer thickness of the shielding material. To complete this optimization study, two PC-controlled radiochemistry systems for the industrial production of 111In and 64Cu have been developed. a) In the 111In radiochemistry system, 111In is produced by irradiation of enriched 112Cd with medium energy protons (i.e. 24.3 MeV). The system includes the time-controlled preparation of the high quality enriched 112Cd targets layers by the constant current electrolysis technique from an alkaline ammonia bath. Upon irradiation the 112Cd target layer containing 111In, is stripped from the copper carrier in a flow-through stripper. Further on, analytical separation techniques like co-precipitation, solvent/solvent extraction and anion exchange chromatography are used for the separation of the no carried added 111In. Tracer experiments using 111In tracer revealed that the overall separation yield is higher than 95%. Photometric and Stripping voltammetric analysis of 111In bulk solutions shows that the chemical quality satisfies the European Pharmacopoeia requirements. The recovery of the enriched 112Cd was done using controlled cathode potential electrolysis, CCPE. Several recovery tests showed that using the CCPE method, the recovery yield is higher than 99.9%.
b) The second developed PC-controlled radiochemistry system is for the separation of no carrier added 64Cu produced by proton irradiation of enriched 64Ni target. To avoid contamination of the final 64Cu bulk with cold copper from the target carrier upon dissolution of the irradiated 64Ni layer, the latter is plated on a gold coated target carrier. The thickness of the 64Ni layer, plated out from alkaline ammonia solutions, amounts to about 62 µm, thickness required to take optimum benefit of the excitation function of the 64Ni(p,n)64Cu threshold reaction when a 64Ni layer target is irradiated with 18 MeV protons in a 6 degree beam/target angle. Upon irradiation 64Ni layer is quantitatively dissolved in a heated flow-through stripper applying 2N nitric acid. Solvent/solvent extraction and ion exchange chromatography techniques are then used to separate efficiently the 64Cu from the 64Ni target material. Using 64Cu as tracer, the efficiency of the radiochemistry system was determined as being about 96%, a quite acceptable value. Taking into account the dilution of the 64Cu bulk prior to dispensing and dose distribution, the chemical purity (Ni <0.003 ppm, Cu <0.005 ppm) of the bulk is acceptable. Recovery of Ni from a partially depleted plating bath and from the combined recovery solutions of four processed 64Ni targets is done by constant current electrolysis, DC¬CCE at 3 A. The recovery yield is excellent (> 99.9%).
Further research should involve testing of the targets and the radiochemistry systems at high beam power, followed by labeling experiments with compounds of biochemical interest i.e. useful for tumour tracing and tumour radiotherapy.
| Datum prijs | 23 jun 2011 |
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| Originele taal | English |
| Begeleider | Alex Hermanne (Promotor), Pierre Van Den Winkel (Promotor), Catherine De Clercq (Jury), Jorgen D'Hondt (Jury), Iris De Graeve (Jury), Jan Danckaert (Jury), D. Schlyer (Jury) & O. Lebeda (Jury) |