Differentielle Zellzykluskontrolle bei Spiraliern und ihre Bedeutung für die Determination der Blastomeren

Bei inäqual furchenden Spiraliern, wie Platynereis dumerilii, entstehen durch die ersten beiden Furchungen vier unterschiedlich große und auch bereits unterschiedlich determinierte Blastomeren. Im allgemeinen ist die größte der vier Blastomeren die Gründerzelle des D-Quadranten (Dorresteijn und Fischer 1988). Dieser Quadrant etabliert die dorsoventrale Körperachse im Keim, indem er das Schicksal benachbarter Blastomeren über Zell-Zell-Interaktionen positionsgerecht bestimmt (Damen und Dictus 1996). Der D-Quadrant erhält bei Platynereis einen überproportional großen Anteil (60%) des gesamten dotterfreien Zytoplasmas im Keim (Dorresteijn 1990). Sein Schicksal wird durch morphogenetische Faktoren innerhalb des dotterfreien Zytoplasmas bestimmt. Der Gehalt an dotterfreiem Zytoplasma bestimmt nicht nur das Schicksal der Blastomeren, sondern korreliert auch direkt mit den jeweils unterschiedlichen Zellzyklusgeschwindigkeiten der Blastomeren. Die plasmareichen Zellen des D-Quadranten, aber auch bereits die Vorläuferzelle CD, teilen sich im Vergleich mit den jeweils anderen Blastomeren im Keim besonders rasch (Dorresteijn 1990). In dieser Arbeit wurde unter verschiedenen Aspekten untersucht (a) inwieweit die Etablierung der dorsoventralen Körperachse von der raschen Proliferation der D-Zellinie abhängt, (b) inwieweit Zellzyklusregulatoren Bestandteil der oben genannten morphogenetischen Faktoren sein könnten und (c) wie die unterschiedlichen Zellzyklusgeschwindigkeiten auf molekularer Ebene reguliert werden.Zum einen wurden die frühen Furchungsstadien von Aplysia californica volumetrisch vermessen. Anders als bei den meisten inäqual furchenden Spiraliern wird bei Aplysia nicht der größte, sondern einer der kleineren embryonalen Quadranten als D-Quadrant determiniert. Ich konnte zeigen, daß die CD-Blastomere (27% des Eivolumens) dennoch, ähnlich wie bei Platynereis, bei der ersten Furchungsteilung überproportional viel dotterfreies Zytoplasma (40%) erhält und so als Vorläuferzelle des D-Quadranten determiniert wird. Bei der zweiten Furchung teilt sich die CD-Blastomere jedoch, anders als bei Platynereis, symmetrisch. Welche der beiden Tochterzellen von CD als definitiver D-Quadrant determiniert wird, erfordert also zusätzliche (induktive?) Mechanismen. Auch bei Aplysia sind die Zellzyklusgeschwindigkeiten der Blastomeren mit ihren jeweiligen Anteilen am dotterfreiem Zytoplasma korreliert. Das Postulat, daß die rasche Proliferation des D-Quadranten und seiner Vorläuferzelle CD für die Etablierung der dorsoventralen Körperachse und für die Determination der Blastomeren in Keimen inäqual furchender Spiralier erforderlich sind, konnte ich zusätzlich bestätigen, indem ich die Teilungsabfolge im Keim von Platynereis mit Hilfe des Cdc2-spezifischen Inhibitors Olomoucin experimentell abänderte. Durch pulse chase-Behandlung mit Olomoucin wurde erreicht, daß die Blastomeren die vierte Mitose, anders als im normalen Keim, synchron einleiteten. Die so behandelten Keime entwickelten sich zu Trochophorae, die keine oder nur eine stark reduzierte dorsoventrale Polarität erkennen ließen. Das dorsoventrale Muster entsteht in Keimen von Spiraliern durch die Organisatorwirkung der Blastomeren 3D und 4d und bei Platynereis eventuell auch 2d (Damen und Dictus 1996, Dorresteijn und Eich 1991). Der Teilungsvorsprung, den diese Blastomeren normalerweise gegenüber anderen Zellinien haben, war in den mit Olomoucin-behandelten Keimen stark vermindert. Dadurch haben diese Blastomeren ihre induktiven Kapazitäten möglicherweise nicht, oder nicht rechtzeitig erwerben können, um die benachbarten Zellen gemäß ihrer Position entlang der dorsoventralen Körperachse zu determinieren. Insofern ist die differentielle Zellzyklusregulation fest in das Determinationsgeschehen integriert. Das bedeutet auch, daß zellzyklusregulierende Faktoren Bestandteil der anfangs genannten

Markierung der Zellinien im Embryo von Platynereis

Die Zellgenealogie des Polychaeten Platynereis dumerilii wurde durch Farbstoffinjektion in die Blastomeren des 2-, 4- und 8-Zellstadiums, sowie die Zellen 2d, 2d112, 4d und 4d1 untersucht. Injektionen gelangen durch Aufweichung der Vitellinhülle mittels Dithioerythritol und Trypsin. Die injizierten Keime wurden zur Trochophora bzw zum dreisegmentigen Jungwurm aufgezogen, fixiert und mit dem konfokalen Rasterlichtmikroskop dreidimensional aufgenommen. Die animal-vegetale Achse des Frühkeims entspricht der antero-posterioren Achse des Jungwurms. Die Mikromeren des ersten Quartetts sind radiär um die antero-posteriore Achse angeordnet und bilden den Kopf. Die Mikromere 2d proliferiert bilateralsymmetrisch von der dorsalen Mittellinie aus und liefert das gesamte Rumpfektoderm. Indirekt ließ sich ableiten, daß die Mikromeren 2a1 bis 2c1 schmale ektodermale Streifen zwischen Kopf und Rumpf bilden und aus 2a2 und 2c2 das ektodermale Stomodaeum hervorgeht. Die Mikromeren des dritten Quartetts sowie möglicherweise 2b2 bilden 'Ektomesoderm'. 4d proliferiert ebenfalls bilateralsymmetrisch von der dorsalen Mittellinie aus zum Rumpfmesoderm und liefert vielleicht noch kleine Beiträge zum Aufbau des Darmes. Der Mitteldarm stammt von den dotterreichen Makromeren 4A bis 4D.

Unconventional correlated systems

This work comprises three different types of unconventional correlated systems.rnChapters 3-5 of this work are about the open shell compounds Rb4O6 and Cs4O6. These mixed valent compounds contain oxygen in two different modifications: the closed-shell peroxide anion is nonmagnetic, whereas the hyperoxide anion contains an unpaired electrons in an antibonding pi*-orbital. Due to this electron magnetic ordering is rendered possible. In contrast to theoretical predictions, which suggested half-metallic ferromagnetism for Rb4O6,rndominating antiferromagnetic interactions were found in the experiment. Besidesrna symmetry reduction due to the mixed valency, strong electronic correlations of this highly molecular system determine its properties; it is a magnetically frustrated insulator. The corresponding Cs4O6 was found to show similar properties.rnChapters 6-9 of this work are about intermetallic Heusler superconductors. rnAll of these superconductors were rationally designed using the van Hove scenario as a working recipe. A saddle point in the energy dispersion curve of a solid leads to a van Hove singularity in the density of states. In the Ni-based and Pd-based Heusler superconductors presented in this work this sort of a valence instability occurs at the high-symmetry L point and coincides or nearly coincides with the Fermi level. The compounds escape the high density of states at the Fermi energy through a transition into the correlated superconducting state.rnChapter 10 of this work is about the tetragonally distorted ferrimagnetic DO22 phase of Mn3Ga. This hard-magnetic modification is technologically useful for spin torque transfer applications. The phase exhibits two different crystallographic sites that are occupied by Mn atoms and can thus be written as Mn2MnGa. The competition between the mainly itinerant moments of the Mn atoms at the Wyckoff position 4d and the localized moments of the Mn atoms at the Wyckoff position 2b leads to magnetic correlations. The antiferromagnetic orientation of these moments determines the compound to exhibit a resulting magnetic moment of approximately 1 µB per formula unit in a partially compensated ferrimagnetic configuration.

N-Heterocyclic carbene complexes of rhodium: structures, dynamics and catalysis

A series of imidazolium salts of the type [BocNHCH2CH2ImR]X (Boc = t-Bu carbamates; Im = imidazole) (R = Me, X = I, 1a; R = Bn, X = Br, 1b; R = Trityl, X = Cl, 1c) and [BnImR’]X (R’ = Me, X = Br, 1d; R’ = Bn, X = Br, 1e; R’ = Trityl, X = Cl, 1g; R’ = tBu, X = Br, 1h) bearing increasingly bulky substituents were synthetized and characterized. Subsequently, these precursors were employed in the synthesis of silver(I)-N-heterocyclic (NHC) complexes as transmetallating reagents for the preparation of rhodium(I) complexes [RhX(NBD)(NHC)] (NHC = 1-(2-NHBoc-ethyl)-3-R-imidazolin-2-ylidene; X = Cl; R = Me, 4a; R = Bn, 4b; R = Trityl, 4c; X = I, R = Me, 5a; NHC = 1-Bn-3-R’-imidazolin-2-ylidene; X = Cl; R’ = Me, 4d, R’ = Bn, 4e, R’ = Trityl, 4g; R’ = tBu, 4h). VT NMR studies of these complexes revealed a restricted rotation barriers about the metal-carbene bond. While the rotation barriers calculated for the complexes in which R = Me, Bn (4a,b,d,e and 5a) matched the experimental values, this was not true for the complexes 4c,g, bearing a trityl group for which the values are much smaller than the calculated ones. Energy barriers for 4c,g, derived from a line shape simulation, showed a strong dependence on the temperature while for 4h the rotational energy barrier is stopped at room temperature. The catalytic activity of the new rhodium compounds was investigated in the hydrosilylation of terminal alkynes and in the addition of phenylboronic acid to benzaldehyde. The imidazolium salts 1d,e were also employed in the synthesis of new iron(II)-NHC complexes. Finally, during a six-months stay at the University of York a new ligand derived from Norharman was prepared and employed in palladium-mediated cross-coupling.

Development and evaluation of a 44 Ti, 44 Sc radionuclide generator and labeling of biomolecules with 44 Sc and 68 Ga for PET imaging

Non-invasive molecular-imaging technologies are playing a key role in drug discovery, development and delivery. Positron Emission Tomography (PET) is such a molecular imaging technology and a powerful tool for the observation of various deceases in vivo. However, it is limited by the availability of vectors with high selectivity to the target and radionuclides with a physical half-life which matches the biological half-life of the observed process. The 68Ge/68Ga radionuclide generator makes the PET-nuclide anywhere available without an on-site cyclotron. Besides the perfect availability 68Ga shows well suited nuclide properties for PET, but it has to be co-ordinated by a chelator to introduce it in a radiopharmaceuticals.rnHowever, the physical half-life of 68Ga (67.7 min) might limit the spectrum of clinical applications of 68Ga-labelled radiodiagnostics. Furthermore, 68Ga-labelled analogues of endoradiotherapeuticals of longer biological half-live such as 90Y- or 177Lu-labeled peptides and proteins cannot be used to determine individual radiation dosimetry directly. rnThus, radionuclide generator systems providing positron emitting daughters of extended physical half-life are of renewed interest. In this context, generator-derived positron emitters with longer physical half-life are needed, such as 72As (T½ = 26 h) from the 72Se/72As generator, or 44Sc (T½ = 3.97 h) from the 44Ti/44Sc generator.rnIn this thesis the implementation of radioactive gallium-68 and scandium-44 for molecular imaging and nuclear medical diagnosis, beginning with chemical separation and purification of 44Ti as a radionuclide mother, investigation of pilot generators with different elution mode, building a prototype generator, development and investigation of post-processing of the generator eluate, its concentration and further purification, the labeling chemistry under different conditions, in vitro and in vivo studies of labeled compounds and, finally, in vivo imaging experiments are described.

Valutazione della qualità delle immagini e della dose in multi-slice computed tomography per l'ottimizzazione dei protocolli clinici che impiegano sistemi di modulazione automatica

In questo studio ci siamo proposti di investigare i sistemi di modulazione automatica della dose sui sistemi TC Multislice (Automatic Exposure Control – AEC) da tre diversi produttori, aventi differenti indicatori di qualità delle immagini. Il presente lavoro è stato svolto presso il Servizio di Fisica Sanitaria dell’Azienda Ospedaliera Universitaria - Policlinico Sant’Orsola-Malpighi di Bologna e consiste in un’analisi quantitativa della dose impiegata durante esami di Tomografia Computerizzata Multi-Slice (TCMS) e delle rispettive immagini radiologiche. Le immagini sono state acquisite con : GE LightSpeed VCT 64 e GE LightSpeed 16 (AEC AutomA 3D longitudinale e angolare), Siemens Sensation 16 (AEC CARE Dose 4D combinato), Philips Brilliance 16 e iCT 64 (separati in AEC ZDOM longitudinale e AEC DDOM angolare). Le acquisizioni TCMS sono state effettuate a differenti kV e mA di riferimento, al fine di investigarne gli effetti sulla modulazione, impiegando algoritmi di ricostruzione standard presenti su ogni macchina. Due fantocci antropomorfi simulanti la zona del torace e dell’addome sono stati utilizzati per simulare un paziente standard posizionato come in un esame clinico di routine ; a questo proposito, sono stati impiegati protocolli elicoidali standard con e senza modulazione. Sono inoltre stati testati differenti valori di indice di qualità delle immagini. Il profilo dei mA lungo la lunghezza è stato ottenuto utilizzando ImageJ, un programma open source comunemente utilizzato per l’elaborazione di immagini; i mAs sono stati normalizzati ad un fattore che tiene conto delle differenti geometrie e delle filtrazioni dei diversi scanner tomografici analizzati nell’esperienza. Il rumore è stato valutato tramite la scelta di determinate ROI (Region Of Interest) localizzate in aree il più possibili uniformi disponibili lungo i fantocci. Abbiamo registrato che una variazione del Noise Index o dei mAs di riferimento a seconda della tipologia di macchina analizzata risulta in uno shift dei profili di dose; lo stesso si è verificato quando sono stati cambiato kV o mA nella scout di acquisizione. Sistemi AEC longitudinali e combinati hanno mostrato profili di mAs normalizzati simili tra loro, con valori elevati evidenziati nella zona delle spalle e zona pelvi; sono state osservate differenze del 30-40% tra i differenti scanner tomografici. Solo in un caso di macchina analizzata si è verificato un comportamento opposto rispetto alle altre due tipologie di macchina in esame. A dispetto della differente natura dei sistemi AEC, i risultati ottenuti dai protocolli combinati e longitudinali sono simili tra loro. Il rumore presente nelle immagini è aumentato ad un livello accettabile e la sua uniformità lungo la direzione di scan è migliorata.

Implementation of a VLSI amplifier interfaced with biomedical sensors for ultra wide band data transmission

This thesis presents a CMOS Amplifier with High Common Mode rejection designed in UMC 130nm technology. The goal is to achieve a high amplification factor for a wide range of biological signals (with frequencies in the range of 10Hz-1KHz) and to reject the common-mode noise signal. It is here presented a Data Acquisition System, composed of a Delta-Sigma-like Modulator and an antenna, that is the core of a portable low-complexity radio system; the amplifier is designed in order to interface the data acquisition system with a sensor that acquires the electrical signal. The Modulator asynchronously acquires and samples human muscle activity, by sending a Quasi-Digital pattern that encodes the acquired signal. There is only a minor loss of information translating the muscle activity using this pattern, compared to an encoding technique which uses astandard digital signal via Impulse-Radio Ultra-Wide Band (IR-UWB). The biological signals, needed for Electromyographic analysis, have an amplitude of 10-100μV and need to be highly amplified and separated from the overwhelming 50mV common mode noise signal. Various tests of the firmness of the concept are presented, as well the proof that the design works even with different sensors, such as Radiation measurement for Dosimetry studies.

Il modello di Kaluza: unificazione tra gravità ed elettromagnetismo

Una teoria di unificazione ha il notevole compito di fornire un modello in grado di unificare le forze fondamentali della natura in una sola. Storicamente uno dei primi tentativi è rappresentato dal modello di Kaluza, che propone una formulazione unificata di gravità ed elettromagnetismo. In 4 dimensioni il campo gravitazionale e il campo elettromagnetico sono entità nettamente separate. Tale dualismo può essere superato estendendo la teoria della Relatività Generale ad uno spaziotempo a 5 dimensioni. Se alle consuete 4 si aggiunge una quinta dimensione spaziale, allora si dimostra che la gravità e l’elettromagnetismo possono essere visti come la manifestazione di un unico campo di forza, che è interpretabile in termini della geometria dello spaziotempo a 5 dimensioni. Nonostante i suoi intrinseci limiti, il modello di Kaluza rappresenta comunque un punto di partenza per molte altre teorie di campo unificato più moderne e a più di 5 dimensioni. L'obiettivo è di sviluppare le linee fondamentali del modello di Kaluza. Preliminarmente si riportano i risultati principali dell'elettromagnetismo e della Relatività Generale, dato che il modello si formula a partire da questi. Si stabilisce la condizione di cilindro, secondo cui le quantità fisiche non subiscono variazioni nella quinta dimensione. Si ipotizza un ansatz per il tensore metrico 5D e si scrivono le equazioni di campo unitario e della geodetica, come estensioni a 5 dimensioni di quelle in 4. Si dimostra che il campo unitario in 4 dimensioni si separa nel campo scalare costante, nel campo elettromagnetico e nel campo gravitazionale. Le componenti quadridimensionali della geodetica 5D riconducono a quella 4D e alle leggi del moto 4D in presenza dei campi gravitazionale ed elettromagnetico. Inoltre si interpreta la carica elettrica come la quinta componente della velocità covariante 5D.

Procedural and dosimetric aspects in peripheral angiography using CO2 as contrast medium

Lo scopo di questa tesi è lo studio degli aspetti procedurali e dosimetrici in angiografie periferiche che utilizzano la CO2 come mezzo di contrasto. La tecnica angiografica consiste nell’imaging radiologico di vasi sanguigni tramite l’iniezione di un mezzo di contrasto, e il suo uso è in costante incremento a causa dell’aumento di pazienti con malattie vascolari. I mezzi di contrasto iodati sono i più comunemente utilizzati e permettono di ottenere immagini di ottima qualità, ma presentano il limite di una elevata nefrotossicità. La CO2 è considerata un’interessante alternativa al mezzo iodato, per la sua acclarata biocompatibilità, soprattutto per pazienti con elevati fattori di rischio (diabete e/o insufficienza renale). Il suo utilizzo presenta comunque alcuni aspetti problematici, dovuti allo stato gassoso e al basso contrasto intrinseco rispetto alla soluzione iodata. Per quest’ultimo motivo si ritiene generalmente che l’utilizzo della CO2 comporti un aumento di dose rispetto ai mezzi di contrasto tradizionali. Il nostro studio, effettuato su diversi apparati radiologici, ha dimostrato che i parametri di emissione radiologica sono gli stessi per i protocolli di angiografia tradizionale, con iodio, e quelli che utilizzano CO2. Questa evidenza suggerisce che i protocolli CO2 operino solo sul trattamento delle immagini ottenute e non sulla modalità di acquisizione, e dal punto di vista dosimetrico l’angiografia con CO2 è riconducibile all’angiografia tradizionale. L’unico fattore che potrebbe portare a un effettivo incremento di dose al paziente è un allungamento dei tempi di scopia e di procedura, che andrebbe verificato con una campagna di misure in ambito clinico. Sulla base della stessa evidenza, si ritiene che la visualizzazione della CO2 possa essere ulteriormente migliorata attraverso l’ottimizzazione dei parametri di emissione radiologica (kVp, frame rate e durata degli impulsi) attualmente predisposti per l’uso di mezzi di contrasto iodati.

Novel materials for direct X-ray detectors based on semiconducting organic polymers

Conventional inorganic materials for x-ray radiation sensors suffer from several drawbacks, including their inability to cover large curved areas, me- chanical sti ffness, lack of tissue-equivalence and toxicity. Semiconducting organic polymers represent an alternative and have been employed as di- rect photoconversion material in organic diodes. In contrast to inorganic detector materials, polymers allow low-cost and large area fabrication by sol- vent based methods. In addition their processing is compliant with fexible low-temperature substrates. Flexible and large-area detectors are needed for dosimetry in medical radiotherapy and security applications. The objective of my thesis is to achieve optimized organic polymer diodes for fexible, di- rect x-ray detectors. To this end polymer diodes based on two different semi- conducting polymers, polyvinylcarbazole (PVK) and poly(9,9-dioctyluorene) (PFO) have been fabricated. The diodes show state-of-the-art rectifying be- haviour and hole transport mobilities comparable to reference materials. In order to improve the X-ray stopping power, high-Z nanoparticle Bi2O3 or WO3 where added to realize a polymer-nanoparticle composite with opti- mized properities. X-ray detector characterization resulted in sensitivties of up to 14 uC/Gy/cm2 for PVK when diodes were operated in reverse. Addition of nanoparticles could further improve the performance and a maximum sensitivy of 19 uC/Gy/cm2 was obtained for the PFO diodes. Compared to the pure PFO diode this corresponds to a five-fold increase and thus highlights the potentiality of nanoparticles for polymer detector design. In- terestingly the pure polymer diodes showed an order of magnitude increase in sensitivity when operated in forward regime. The increase was attributed to a different detection mechanism based on the modulation of the diodes conductivity.

Tetraamine-derived bifunctional chelators for technetium-99m labelling: synthesis, bioconjugation and evaluation as targeted SPECT imaging probes for GRP-receptor-positive tumours

Owing to its optimal nuclear properties, ready availability, low cost and favourable dosimetry, (99m)Tc continues to be the ideal radioisotope for medical-imaging applications. Bifunctional chelators based on a tetraamine framework exhibit facile complexation with Tc(V)O(2) to form monocationic species with high in vivo stability and significant hydrophilicity, which leads to favourable pharmacokinetics. The synthesis of a series of 1,4,8,11-tetraazaundecane derivatives (01-06) containing different functional groups at the 6-position for the conjugation of biomolecules and subsequent labelling with (99m)Tc is described herein. The chelator 01 was used as a starting material for the facile synthesis of chelators functionalised with OH (02), N(3) (04) and O-succinyl ester (05) groups. A straightforward and easy synthesis of carboxyl-functionalised tetraamine-based chelator 06 was achieved by using inexpensive and commercially available starting materials. Conjugation of 06 to a potent bombesin-antagonist peptide and subsequent labelling with (99m)Tc afforded the radiotracer (99m)Tc-N4-BB-ANT, with radiolabelling yields of >97% at a specific activity of 37 GBq micromol(-1). An IC(50) value of (3.7+/-1.3) nM was obtained, which confirmed the high affinity of the conjugate to the gastrin-releasing-peptide receptor (GRPr). Immunofluorescence and calcium mobilisation assays confirmed the strong antagonist properties of the conjugate. In vivo pharmacokinetic studies of (99m)Tc-N4-BB-ANT showed high and specific uptake in PC3 xenografts and in other GRPr-positive organs. The tumour uptake was (22.5+/-2.6)% injected activity per gram (% IA g(-1)) at 1 h post injection (p.i.). and increased to (29.9+/-4.0)% IA g(-1) at 4 h p.i. The SPECT/computed tomography (CT) images showed high tumour uptake, clear background and negligible radioactivity in the abdomen. The promising preclinical results of (99m)Tc-N4-BB-ANT warrant its potential candidature for clinical translation.

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.

Effectiveness of protective patient equipment for CT: an anthropomorphic phantom study

Protective patient equipment for CT examinations is not routinely provided. The aim of this study was to determine whether, and if so what, specific protective equipment is beneficial during CT scans. The absorbed organ doses and the effective doses for thorax, abdomen/pelvis and brain CT investigation with and without the use of protective patient equipment have been determined and compared. All measurements were carried out on modern multislice CT scanner using an anthropomorphic phantom and thermoluminescence dosemeters. The measurements show that protective equipment reduces the dose within the scattered beam area. The highest organ dose reduction was found in organs that protrude from the trunk like the testes or the female breasts that can largely be covered by the protective equipment. The most reduction of the effective dose was found in the male abdomen/pelvis examination (0.32 mSv), followed by the brain (0.11 mSv) and the thorax (0.06 mSv). It is concluded that the use of protective equipment can reduce the applied dose to the patient.

Generation and characterization of stable, highly concentrated titanium dioxide nanoparticle aerosols for rodent inhalation studies

The intensive use of nano-sized titanium dioxide (TiO2) particles in many different applications necessitates studies on their risk assessment as there are still open questions on their safe handling and utilization. For reliable risk assessment, the interaction of TiO2 nanoparticles (NP) with biological systems ideally needs to be investigated using physico-chemically uniform and well-characterized NP. In this article, we describe the reproducible production of TiO2 NP aerosols using spark ignition technology. Because currently no data are available on inhaled NP in the 10–50 nm diameter range, the emphasis was to generate NP as small as 20 nm for inhalation studies in rodents. For anticipated in vivo dosimetry analyses, TiO2 NP were radiolabeled with 48V by proton irradiation of the titanium electrodes of the spark generator. The dissolution rate of the 48V label was about 1% within the first day. The highly concentrated, polydisperse TiO2 NP aerosol (3–6 × 106 cm−3) proved to be constant over several hours in terms of its count median mobility diameter, its geometric standard deviation, and number concentration. Extensive characterization of NP chemical composition, physical structure, morphology, and specific surface area was performed. The originally generated amorphous TiO2 NP were converted into crystalline anatase TiO2 NP by thermal annealing at 950 °C. Both crystalline and amorphous 20-nm TiO2 NP were chain agglomerated/aggregated, consisting of primary particles in the range of 5 nm. Disintegration of the deposited TiO2 NP in lung tissue was not detectable within 24 h.

Alpha- versus beta-particle radiopeptide therapy in a human prostate cancer model (213Bi-DOTA-PESIN and 213Bi-AMBA versus 177Lu-DOTA-PESIN)

Recurrent prostate cancer presents a challenge to conventional treatment, particularly so to address micrometastatic and small-volume disease. Use of α-radionuclide therapy is considered as a highly effective treatment in such applications due to the shorter range and exquisite cytotoxicity of α-particles as compared with β-particles. (213)Bi is considered an α-emitter with high clinical potential, due to its short half-life (45.6 minutes) being well matched for use in peptide-receptor radionuclide α-therapy; however, there is limited knowledge available within this context of use. In this study, two novel (213)Bi-labeled peptides, DOTA-PEG(4)-bombesin (DOTA-PESIN) and DO3A-CH(2)CO-8-aminooctanoyl-Q-W-A-V-G-H-L-M-NH(2) (AMBA), were compared with (177)Lu (β-emitter)-labeled DOTA-PESIN in a human androgen-independent prostate carcinoma xenograft model (PC-3 tumor). Animals were injected with (177)Lu-DOTA-PESIN, (213)Bi-DOTA-PESIN, or (213)Bi-AMBA to determine the maximum tolerated dose (MTD), biodistribution, and dosimetry of each agent; controls were left untreated or were given nonradioactive (175)Lu-DOTA-PESIN. The MTD of (213)Bi-DOTA-PESIN and (213)Bi-AMBA was 25 MBq (0.68 mCi) whereas (177)Lu-DOTA-PESIN showed an MTD of 112 MBq (3 mCi). At these dose levels, (213)Bi-DOTA-PESIN and (213)Bi-AMBA were significantly more effective than (177)Lu-DOTA-PESIN. At the same time, (177)Lu-DOTA-PESIN showed minimal, (213)Bi-DOTA-PESIN slight, and (213)Bi-AMBA marked kidney damage 20 to 30 weeks posttreatment. These preclinical data indicate that α-therapy with (213)Bi-DOTA-PESIN or (213)Bi-AMBA is more efficacious than β-therapy. Furthermore, (213)Bi-DOTA-PESIN has a better safety profile than (213)Bi-AMBA, and represents a possible new approach for use in peptide-receptor radionuclide α-therapy treating recurrent prostate cancer.