Im Rahmen dieser Arbeit wurde eine Frisch-Gitterionisationskammer zum Messen kleinster spezifischer Alphaaktivitäten realisiert. Im konkreten Fall soll der Detektor dafür genutzt werden, die Halbwertszeit von 144Nd erneut zu bestimmen. Da diese sehr lang (T1/2 = (2,29 ± 0,16) · 10^15 Jahre) und die Reichweite der emittierten Alphateilchen in Feststoffen sehr gering ist, können nur sehr dünne Proben untersucht werden. Die Fläche der Proben sollte sehr groß sein, um die nötige Aktivität zu erhalten. Im Vergleich haben sich Gitterionisationskammern als das geeignetste Detektorkonzept erwiesen. Es wurde eine Kammer realisiert, welche aus zwei Gitterionisationskammern mit geteilter Anode besteht. Mit Hilfe dieses Aufbaus ist es möglich den Detektornulleffekt zu reduzieren. Die Auslese der auf den Detektorelektroden induzierten Ladung erfolgt mit Hilfe eines Analog-Digital-Konverters. Die Auswertung der gewonnenen Daten wird vollständig nach der Messung durchgeführt. Anhand einer Pulsformanalyse können verschiedene Informationen über jedes, im Detektor stattgefundene, Ereignis gewonnen werden. So ist es möglich den Gitterdurchgriff und die damit verbundene Winkelabhängigkeit der Pulshöhen zu korrigieren und somit die Energieauflösung des Detektors zu verbessern. Es wird eine Energieauflösung von 0,86 % bei 5,1 MeV erreicht. Die Charakterisierung der Ereignisse wird außerdem für die Reduktion des Detektornulleffekts herangezogen. Aufgrund verschiedener Bedingungen, die für ein zu erwartendes Alphaereignis notwendig sind, kann ein Großteil der, die Messung störenden Ereignisse, unterdrückt werden. So kann der Nulleffekt im Energiebereich von 1 MeV bis 2,2 MeV von 435 Ereignissen pro Tag ohne Charakterisierung um etwa ein Faktor 20 auf 21,6 Ereignisse pro Tag mit Charakterisierung reduziert werden. Die Nachweiseffizienz wird davon nicht merklich beeinträchtigt. Für ausreichend lange Messzeiten ist eine Nachweisgrenze von weniger als 10 Ereignissen pro Tag zu erwarten. Für eine, für diesen Aufbau geeignete, Targetgeometrie ist mit etwa 50 Alphazerfällen des 144Nd pro Tag zu rechnen. Mit einer Nachweiseffizienz von etwas unter 50 % sollte die Messung am 144Nd gut möglich sein. / The realization of this work was the usage of a Frisch grid ionization chamber for measuring the lowest specific alpha activity. In the practical case the detector should be used to remeasure the half life of 144Nd. Only very thin targets can be used, due to the extreme long half life and the very short range of alpha particles in matter. The area of the samples must be big enough to get the required activity. In comparison gridded ionization chambers are the most practical devices. The chamber was realized in that way, that two gridded chambers shares a common anode. This could be used to minimize the detector background. The charge, which was induced in the detector electrodes, is acquired by an analog to digital converter. The full analysis of the data is done after the measurement. With the pulse form analysis it is possible to extract information about every event occurring in the detector. It is also possible to correct the grid inefficiency and the correlated angle dependence of the pulse height. This improves the energy resolution. A resolution of 0.86 % at 5.1 MeV is possible. The characterization of the events is also used for the suppression of the detector background. Due to different conditions for an assumed alpha event the majority of the events which disturbs the measurement could be removed. So it is possible to suppress the background in the range between 1 MeV to 2.2 MeV of 435 events per day without the characterization to 21.6 events per day with characterization, which is a factor of roughly 20. The detection efficiency is not noticeably effected. For sufficiently long measurements a lowest limit of detection of 10 counts per day is expectable. For a target geometry which can be used with this setup, about 50 alpha decays of 144Nd per day will occur. With a detection efficiency a bit below 50 % the measurement on Nd should be possible.

The most promising applications for targeted alpha-therapy with astatine-211 (At-211) include treatments of disseminated microscopic disease, the major medical problem for cancer treatment. The primary advantages of targeted alpha-therapy with At-211 are that the alpha-particle radiation is densely ionizing, translating to high relative biological effectiveness (RBE), and short-range, minimizing damage to surrounding healthy tissues. In addition, theranostic imaging with I-123 surrogates has shown promise for developing new therapies with At-211 and translating them to the clinic. Currently, Canada does not have a way of producing At-211 by conventional methods because it lacks alpha-particle accelerators with necessary beam energy and intensity. The work presented here was aimed at studying the Rn-211/At-211 generator system as an alternative production strategy by leveraging TRIUMF's ability to produce rare isotopes. Recognizing that TRIUMF provided production opportunities for a variety of astatine isotopes, this work also originally hypothesized and evaluated the use of At-209 as a novel isotope for preclinical Single Photon Emission Computed Tomography (SPECT) with applications to At-211 therapy research. At TRIUMF's Isotope Separator and Accelerator (ISAC) facility, mass separated ion beams of short­-lived francium isotopes were implanted into NaCl targets where Rn-211 or At-209 were produced by radioactive decay, in situ. This effort required methodological developments for safely relocating the implanted radioactivity to the radiochemistry laboratory for recovery in solution. For multiple production runs, Rn-211 was quantitatively transferred from solid NaCl to solution (dodecane) from which At-211 was efficiently extracted and evaluated for clinical applicability. This validated the use of dodecane for capturing Rn-211 as an elegant approach to storing and shipping Rn-211/At-211 in the future. Po-207 contamination (also produced by Rn-211 decay) was removed using a granular tellurium (Te) column before proceeding with biomolecule labelling. Although the produced quantities were small, the pure At-211 samples demonstrated these efforts to have a clear path of translation to animal studies. For the first time in history, SPECT/CT was evaluated for measuring At-209 radioactivity distributions using high energy collimation. The spectrum detected for At-209 by the SPECT camera presented several photopeaks (energy windows) for reconstruction. The 77-90 Po X­-ray photopeak reconstructions were found to provide the best images overall, in terms of resolution/contrast and uniformity. Collectively, these experiments helped establish guidelines for determining the optimal injected radioactivity, depending on scan parameters. Moreover, At-209-based SPECT demonstrated potential for pursuing image-­based dosimetry in mouse tumour models, in the future. Simultaneous SPECT imaging with At-209 and I-123 was demonstrated to be feasible, supporting the future evaluation of At-209 for studying/validating I-123 surrogates for clinical image-based At-211 dosimetry. This work also pursued a novel strategy for labelling cancer targeting peptides with At-211, using octreotate (TATE, a somatostatin analogue for targeting tumour cells, mostly neuroendocrine tumours) prepared with or without N-terminus PEGylation (PEG2), followed by conjugation with a closo-decaborate linking moiety (B10) for attaching At-211. Binding affinity and in vivo biodistributions for the modified peptides were determined using iodine surrogates. The results indicated that B10-PEG2-TATE retained target binding affinity but that the labelling reaction with iodine degraded this binding affinity significantly, and although having high in vivo stability, no I-123-B10-PEG2-TATE tumour uptake was observed by SPECT in a mouse tumour model positive for the somatostatin receptor (sstr2a). This suggested that further improvements are required for labelling. A new method for producing At-211 at TRIUMF is established, and At-209-­based SPECT imaging is now demonstrated as a new preclinical technology to measure astatine biodistributions in vivo for developing new radiopharmaceuticals with At-211. Combined with the theranostic peptide labelling efforts with iodine, these efforts provide a foundation for future endeavours with At-211-­based alpha-therapy at TRIUMF. All procedures were performed safely and rapidly, suitable for preclinical evaluations. All animal studies received institutional ethics approval from the University of British Columbia (UBC). / Graduate