Applications of metrological techniques for clinical implementation of dosimetry and radiobiology in molecular radiotherapy

Molecular radiotherapy (MRT) is a fast developing and promising treatment for metastasised neuroendocrine tumours. Efficacy of MRT is based on the capability to selectively "deliver" radiation to tumour cells, minimizing administered dose to normal tissues. Outcome of MRT depends on the individual patient characteristics. For that reason, personalized treatment planning is important to improve outcomes of therapy. Dosimetry plays a key role in this setting, as it is the main physical quantity related to radiation effects on cells. Dosimetry in MRT consists in a complex series of procedures ranging from imaging quantification to dose calculation. This doctoral thesis focused on several aspects concerning the clinical implementation of absorbed dose calculations in MRT. Accuracy of SPECT/CT quantification was assessed in order to determine the optimal reconstruction parameters. A model of PVE correction was developed in order to improve the activity quantification in small volume, such us lesions in clinical patterns. Advanced dosimetric methods were compared with the aim of defining the most accurate modality, applicable in clinical routine. Also, for the first time on a large number of clinical cases, the overall uncertainty of tumour dose calculation was assessed. As part of the MRTDosimetry project, protocols for calibration of SPECT/CT systems and implementation of dosimetry were drawn up in order to provide standard guidelines to the clinics offering MRT. To estimate the risk of experiencing radio-toxicity side effects and the chance of inducing damage on neoplastic cells is crucial for patient selection and treatment planning. In this thesis, the NTCP and TCP models were derived based on clinical data as help to clinicians to decide the pharmaceutical dosage in relation to the therapy control and the limitation of damage to healthy tissues. Moreover, a model for tumour response prediction based on Machine Learning analysis was developed.

Hybrid lead-halide perovskites as novel materials for thin film direct and flexible ionizing radiation detectors

Ionizing radiations are important tools employed every day in the modern society. For example, in medicine they are routinely used for diagnostic and therapy. The large variety of applications leads to the need of novel, more efficient, low-cost ionizing radiation detectors with new functionalities. Personal dosimetry would benefit from wearable detectors able to conform to the body surfaces. Traditional semiconductors used for ionizing radiation direct detectors offer high performance but they are intrinsically stiff, brittle and require high voltages to operate. Hybrid lead-halide perovskites emerged recently as a novel class of materials for ionizing radiation detection. They combine high absorption coefficient, solution processability and high charge transport capability, enabling efficient and low-cost detection. The deposition from solution allows the fabrication of thin-film flexible devices. In this thesis, I studied the detection properties of different types of hybrid perovskites, deposited from solution in thin-film form, and tested under X-rays, gamma-rays and protons beams. I developed the first ultraflexible X-ray detector with exceptional conformability. The effect of coupling organic layers with perovskites was studied at the nanoscale giving a direct demonstration of trap passivation effect at the grain boundaries. Different perovskite formulations were deposited and tested to improve the film stability. I report about the longest aging studies on perovskite X-ray detectors showing that the addition of starch in the precursors’ solution can improve the stability in time with only a 7% decrease in sensitivity after 630 days of storage in ambient conditions. 2D perovskites were also explored as direct detector for X-rays and gamma-rays. Detection of 511 keV photons by a thin-film device is here demonstrated and was validated for monitoring a radiotracer injection. At last, a new approach has been used: a 2D/3Dmixed perovskite thin-film demonstrated to reliably detect 5 MeV protons, envisioning wearable dose monitoring during proton/hadron therapy treatments.