CERN Accelerating science

Thesis
Report number	CERN-THESIS-2020-257
Title	Production of mass separated $^{11}$C beams for PET-aided hadron therapy
Author(s)	Stegemann, Simon (KU Leuven)
Thesis note	PhD : KU Leuven : 2020
Thesis supervisor(s)	Cocolios, Thomas Elias
Note	Presented 31 Aug 2020
Subject category	Accelerators and Storage Rings ; Health Physics and Radiation Effects
Accelerator/Facility, Experiment	CERN ISOLDE
Study	MEDICIS
Abstract	Ever since the first discovery of an artificially-generated radionuclide, the production of radioisotopes and radioactive ion beams has been an essential tool in nuclear physics research for the study of the atomic nucleus and its properties. Furthermore, the very same discovery is considered as one of the cornerstones in nuclear medicine, where radioisotopes are exploited for the diagnosis and therapy of cancer. This thesis liaises these two fields by utilizing the concept of radioactive ion beam production for the development of a $^{11}$C based hadron therapy protocol. Hadron therapy, and particularly $^{12}$C therapy is a promising treatment modality for non-metastatic cancers, which uses energetic ion beams to irradiate the tumor, and which allows to distribute the dose to the cancerous tissue while sparing the surrounding healthy tissue. One of the main obstacles in the success of hadron therapy is the correct prediction of the ion beam's range, which in practice suffers from significant uncertainties. \textit{In vivo} range verification based on PET-imaging techniques is considered as a promising method to overcome this hurdle. This thesis is dedicated to such an approach where the stable $^{12}$C beam is replaced by its $\beta^+$-emitting radioisotope $^{11}$C, which thus allows to combine hadron therapy with on-line PET-imaging. The main difficulty in this respect is the production of a sufficiently intense $^{11}$C radioactive ion beam, since effective treatments require $\sim 4 \cdot 10^8$ ions per second delivered to the patient. To date, no radioactive ion beam production system exists that can be implemented into existing treatment facilities and which meets the aforementioned beam intensity requirement with appropriate beam properties. It was therefore the objective to develop such a system. For this purpose, the isotope separation on-line method was selected, specifically for the production of intense mass separated $^{11}$CO$^+$ beams. A target-ion source unit tailored for $^{11}$CO$^+$ production was developed, which comprises a porous boron nitride target, operated with a controlled oxygen leak, and an electron cyclotron ion source. The main focus of this thesis was the fabrication and systematic characterization of the porous boron nitride target with a controlled microstructure for enhanced $^{11}$C release efficiency. Spark plasma sintering was employed as processing route, yielding a rigid pre-sintered powder compact with $21\%$ open porosity and an average grain size of $1.7\ \mu \textrm{m}$. The porous BN target was characterized with respect to its operational limitations in high temperatures and controlled oxidizing atmospheres, where the applicability of temperatures up to $1500\ \degree \textrm{C}$ and oxygen potentials below $-300\ \textrm{kJ mol}^{-1}$ was proven. A 10$\%$ release efficiency of $^{11}$C from the BN target operated at the aforementioned conditions was extrapolated from an off-line fractional release study performed at CERN MEDICIS, by exploiting the aforementioned microstructural properties obtained from systematic target characterization studies. A conceptual study, examining possible implementation scenarios of the developed $^{11}$CO$^+$ production system into existing hadron therapy centers, demonstrated its feasibility of producing sufficiently intense $^{11}$CO$^+$ radioactive ion beams, which as a result ensure the delivery of the required beam intensity to the patient room after beam manipulation and post-acceleration.

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