In the last decades, the sources of ionizing radiation have been used more and in various branches of medicine, industries, agriculture and research. Like each human activity, the usage of the sources of ionizing radiation is also connected with possible occurrences of accidents and emergencies. Such events can then cause damage to a person health or the environment . The usage of sources of ionizing radiation belongs to those few human activities in the world, where a big attetion is paid not only to the development of appli-cations but also to their safety. However, despite all of it, it is not possible to eliminate the risk of accidents and emergencies. Recently, there has been some talk of possible misuses of the sources of ionizing radiation. Such extraordinary events place high on the first response forces. One of the first re-sponse forces is Fire Rescue Service of the Czech Republic, the forces of which are lo-cated over the Cezch Republic. This thesis shall provide these forces with such infor-mation that they should be able, along with the authorities responsible for the radiation protection, to evaluate the situation and minimise effects on health, lives and environ-ment in the event of radiation extraordinary event. The purpose of this thesis is to solve local extraordinary radiation events (such as acci-dents during the transport of the sources of ionizing radiation, discovery of an unknown radiator). It does not deal with nuclear emergencies and accidents of other equipment, where the scope of the event and its consequences are of nation-wide importance. The first part of the thesis includes basic terms of the ionizing radiation and radiation pro-tection. The other part is focused on the radiation research, monitoring, response system and dosimetry devices. This part also includes materials for trainings and drills focusing on early identification of raiation hazards of an extraordinary event.

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Inorganic colloids are ubiquitous in environmental waters and are thought to be potential transporters of radionuclides and other toxic metals. Colloids present large surface areas to pollutants and contaminants present in waters and are therefore capable of sorbing and transporting them via groundwater and surface water movement. Much research has been and is currently being undertaken to understand more fully the stability of colloids in different water chemistries, factors which affect metal sorption onto colloids, and the processes which affect metal-colloid transport. This thesis first investigates ground water and surface water sampling and characterisation techniques for the investigation of the colloids present in and around a low-level waste repository. Samples were collected anaerobically using micro-purge low-flow methodology (MPLF) and then subjected to sequential ultrafiltration, again anaerobically. After separation into size fractions the solids were analysed for radiochemical content, colloid population and morphology. It was found that colloids were present in large numbers in the groundwaters extracted from the trench waste burial area (anaerobic environment), but in the surface drain waters (aerobic environment) colloid population was comparable t6 levels found in waters extracted from' above the trenches. There was evidence that the non-tritium activity was associated with the colloids and particulates in the trenches, but outside of the trenches the evidence was not conclusive because the activity and colloid concentrations were low. Secondly this thesis investigates the stability of inorganic colloids, mainly haematite, in the presence of humic acid, varying pH and electrolyte concentrations. The applicability of the Schulze-Hardy rule to haematite and haematitelhumic acid mixtures was investigated using photon correlation spectroscopy to measure the rate of fast and slow coagulation after the addition of mono, di and trivalent ions. It was found that humic coated colloids follow the Schulze-Hardy rule for mono and divalent cations, with the exception of copper ions. Trivalent ions do not follow the Schulze-Hardy rule because of their relatively strong complexation with humates. It was also found that the size of the ion has an effect on destabilisation, irrespective of charge.

Abstract A large body of animal studies indicates that reinforcement from alcohol is associated with dopaminergic neurotransmission in the mesocorticolimbic pathway. However, as most psychiatric phenomena cannot be studied with animals, human studies are needed. Furthermore, because of the fluctuating nature of phenomena regarding the status of abuse and withdrawal, repeated observations of the same study subjects under different situations can elucidate a variety of pathophysiological mechanisms. In this study 42 alcoholics were monitored during withdrawal and 30 alcoholics after four weeks of abstinence. 123I-β-CIT SPET was used as a method for the semi quantification of their striatal dopamine transporter (DAT) densities reflecting the function and structure of the dopaminergic system. DAT density was markedly lower during withdrawal among alcoholics as compared to control subjects, but it elevated during abstinence to the level of healthy volunteers. This increases in DAT density during withdrawal and afterwards correlated with the depression scores of alcoholics. DAT density correlated with the Novelty Seeking (NS) personality trait, especially among abstinent alcoholics. After four weeks of controlled abstinence alcoholics with an A1 allele of dopamine receptor D2 were found to have higher DAT densities than alcoholics without it. The results indicate that striatal DAT density is associated with mood, personality, A1 genotype and the length of the abstinence period after heavy alcohol drinking.

ABD-Derived Affinity Proteins (ADAPTs) is a novel class of small engineered scaffold proteins based on albumin-binding domain (ABD) of streptococcal protein G. High affinity ADAPT  binders against various therapeutic targets can be selected.  In this thesis, we report a development of ADAPT-based radionuclide imaging agents providing high sensitivity and specificity of molecular imaging of HER2 expression in disseminated cancers. We investigated the feasibility of the use of ADAPTs as imaging agents and influence of molecular design and radiolabeling chemistry on in vivo targeting and biodistribution properties of the tracers. In Paper I we demonstrated the feasibility of the use of anti-HER2 ADAPT6 molecule as a high contrast imaging agent; In Paper II we evaluated the influence of composition of histidine-containing tag on in vivo biodistribution of ADAPT-based tracers labeled with 99mTc using 99mTc(CO)3 binding to histidine-containing tags and 111In using DOTA chelator at N-terminus; In Paper III we evaluated the influence of different aspects of N-terminus leading sequence on targeting including effect of sequence size on clearance rate and effect of the composition of the sequence on biodistribution profile; In Paper IV, we evaluated the influence of residualizing properties and positioning of the label on biodistribution and targeting; and In Paper V, we compared tumor-targeting properties of the ADAPT6 labeled at C-terminus with 99mTc using N3S chelator and 111In using DOTA chelator. In conclusion, ADAPTs constitute a very promising class of targeting probes for molecular imaging providing high contrast. Molecular design of the ADAPT proteins and chelators/linkers for labeling has an appreciable effect on their imaging properties.

Targeted radionuclide therapy is becoming a widely used cancer treatment strategy. By radiolabeling receptor-specific peptides, cancer cells overexpressing the receptor can be selectively targeted, and the cytotoxic radionuclide can be delivered to the target cell or tissue for therapeutic or diagnostic purposes. Bombesin analogues have been previously developed and utilized to target the gastrin-releasing peptide receptor (GRPR), a receptor commonly overexpressed in prostate cancer cells. The RM26 analogue derived from the native bombesin is an antagonistic ligand of GRPR and a possible candidate for targeted radiotherapy. Prolonging the half-life of the molecule is an important aspect of developing a new protein therapeutic. Using albumin binding domain (ABD) for this purpose is an emerging strategy in recent years. ABD is able to bind to serum albumin and thus remains in the blood circulation for a long period of time. It is also a scaffold for protein engineering efforts and by coupling receptor-specific ligands to ABD, the target-specific binding along with extended in vivo halflife can be achieved. In this project, an RM26 analogue with a PEG linker and ABD with a DOTA chelator for future radiolabeling were synthesized with solid phase peptide synthesis (SPPS), conjugated, purified by RP-HPLC and analyzed by mass spectrometry. The binding properties of the conjugate were evaluated by SPR-based biosensory studies, and further experiments are planned for the testing the product and its potential application in radionuclide therapy. / Riktad radioterapi är en allt vanligare metod för behandling av cancer. Genom att radioinmärka receptor-specifika peptider kan dessa selektivt levereras till tumörceller som uttrycker receptorn. Radioterapi kan användas för diagnostik eller terapi, beroende på kopplad radionuklid. Bombesinanaloger har utvecklats och använts för att selektivt binda gastrinfrisättande peptidreceptor (gastrin-releasing peptide receptor, GRPR), en receptor som ofta är överuttryckt i prostatacancer. Bombesinanalogen RM26, som har sitt ursprung från nativt bombesin, är en antagonist till GRPR och kan möjligen användas för riktad radioterapi av prostatacancer. Vid utvecklingen av nya proteinläkemedel är halveringstiden i serum en viktig aspekt. En nyligen utvecklad strategi för att förlänga halveringstiden i serum är fusion av det  tumörspecifika proteinet till en albumin-bindande domän (ABD). ABD binder till albumin, ochsåledes kan fusionsproteinet bevaras i blodcirkulationen under en längre tid. I detta projekt, har både RM26 med en PEG-linker, och ABD med en DOTA kelator syntetiserats med fastfaspeptidsyntes (solid phase peptide synthesis, SPPS). RM26-PEG och DOTA-ABD har därefter konjugerats, renats med RP-HPLC och analyserats med massspektrometri. Bindning till albumin har utvärderats med ytplasmonresonans (surface plasmon resonance, SPR). Vidare studier planeras för att utvärdera peptid-proteinkonjugatet och dess potential för riktad radioterapi.

Background: Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine. Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH). Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic “Working Group Radiochemistry and Radiopharmacy” (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN. Results: In total, 42 cyclotrons were identified that are currently being operated for medical radionuclide production for imaging and therapy in Nuclear Medicine clinics, 32 of them in Germany, 4 in Austria and 6 in Switzerland. Two thirds of the cyclotrons reported (67%) are operated by universities, university hospitals or research institutions close to a university hospital, less by/in cooperation with industrial partners (29%) or a non-academic clinic/ PET-center (5%). Most of the cyclotrons (88%) are running with up to 18 MeV proton beams, which is sufficient for the production of the currently most common cyclotron-based radionuclides for PET imaging. Discussion: The data presented provide an academically-updated overview of the medical cyclotrons operated for the production of radiopharmaceuticals and their use in Nuclear Medicine in the D-A-CH countries. In this context, we discuss current developments and trends with a view to the cyclotron infrastructure in these countries, with a specific focus on organizational aspects.

Recent years have seen the establishment of several radionuclides as medicinal products in particular in the setting of theranostics and PET. [177Lu]Lutetium Chloride or [64Cu]Copper Chloride have received marketing authorization as radionuclide precursor, [68Ga]Gallium Chloride has received regulatory approval in the form of different 68Ge/68Ga generators. This is a formal requirement by the EU directive 2001/83, even though for some of these radionuclide precursors no licensed kit is available that can be combined to obtain a final radiopharmaceuticals, as it is the case for Technetium-99m. In view of several highly promising, especially metallic radionuclides for theranostic applications in a wider sense, the strict regulatory environment poses the risk of slowing down development, in particular for radionuclide producers that want to provide innovative radionuclides for clinical research purposes, which is the basis for their further establishment. In this paper we address the regulatory framework for novel radionuclides within the EU, the current challenges in particular related to clinical translation and potential options to support translational development within Europe and worldwide.