991 resultados para Radiology, nuclear medicine


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This study examined the effect of fast-velocity concentric isokinetic resistance training (FV) on the rate of force development (RFD) at early (<100ms) and late phases (>100ms) of rising muscle force. Nine men participated in a 6-week resistance training intervention for the lower body, and nine matched subjects participated as controls (CON). During concentric isokinetic (180s-1) knee extension training, subjects were instructed to do each contraction 'as fast and forcefully as possible'. Maximal muscle strength (MVC) and RFD (0-10, 0-20, ..., 0-250ms from the onset of contraction) were measured during maximal voluntary isometric contraction of the knee extensors (KE). There were no significant changes in MVC of KE in both groups after intervention (FV=31421011 versus 3387880N{bullet operator}m, P>005; CON=2933948 versus 2800 722N{bullet operator}m, P>005). The RFD increased 39-71% at time intervals up to 90ms from the onset of the contraction (P<005), whereas no change occurred at later time intervals. Similarly, relative RFD (i.e.%MVC{bullet operator}s-1) (RFDr) increased 33-56% at time intervals up to 70ms from the onset of the contraction (P<005). It can be concluded that a short period of resistance training performed with concentric fast-velocity isokinetic muscle contractions is able to enhance RFD and RFDr obtained at the early phase of rising muscle force. 2013 The Authors Clinical Physiology and Functional Imaging 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

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The purpose of this study was to investigate the influence of exercise order on one-repetition maximum (1-RM) and ten-repetition maximum (10-RM) strength gains after 6 weeks of resistance training (RT) in trained men. Sixteen men were randomly assigned into two groups based on the order of exercises performed during training sessions: a group that performed large muscle group exercises first and progressed to small muscle group exercises (LG-SM); while a second group performed the opposite sequence and started with small muscle group exercises and progressed to large muscle group exercises (SM-LG). Four sessions of RT were conducted per week; all exercises were performed for three sets of 8-12 repetitions with 1-min rest intervals between sets. Maximal and submaximal strength were assessed at baseline and after 6 weeks of RT with 1-RM and 10-RM testing for the bench press (BP), lat pulldown (LPD), triceps pulley extension (TE) and biceps curl (BC), respectively. Two-way ANOVA for the 1-RM and 10-RM tests indicated a significant group x time interaction. The 1-RM values significantly increased for all exercises in both groups (P<0.05), but were not significantly different between groups. However, effect size (ES) data indicated that the LG-SM group exhibited a greater magnitude of gains (1-RM and 10-RM) for the BP and LPD exercises. Conversely, ES indicated that the SM-LG group exhibited a greater magnitude of gains (1-RM and 10-RM) for the TE and BC exercises. In conclusion, the results suggest that upper body movements should be prioritized and performed according to individual needs to maximize maximal and submaximal strength. 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine.

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Ps-graduao em Biologia Geral e Aplicada - IBB

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Ps-graduao em Pesquisa e Desenvolvimento (Biotecnologia Mdica) - FMB

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The SPECT (Single Photon Emission Computed Tomography) systems are part of a medical image acquisition technology which has been outstanding, because the resultant images are functional images complementary to those that give anatomic information, such as X-Ray CT, presenting a high diagnostic value. These equipments acquire, in a non-invasive way, images from the interior of the human body through tomographic mapping of radioactive material administered to the patient. The SPECT systems are based on the Gamma Camera detection system, and one of them being set on a rotational gantry is enough to obtain the necessary data for a tomographic image. The images obtained from the SPECT system consist in a group of flat images that describe the radioactive distribution on the patient. The trans-axial cuts are obtained from the tomographic reconstruction techniques. There are analytic and iterative methods to obtain the tomographic reconstruction. The analytic methods are based on the Fourier Cut Theorem (FCT), while the iterative methods search for numeric solutions to solve the equations from the projections. Within the analytic methods, the filtered backprojection (FBP) method maybe is the simplest of all the tomographic reconstruction techniques. This paper's goal is to present the operation of the SPECT system, the Gamma Camera detection system, some tomographic reconstruction techniques and the requisites for the implementation of this system in a Nuclear Medicine service

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The 131I (radioactive iodine) is one of the most used radionuclides in nuclear medicine for diagnosis and treatment. The present study evaluates the dosimetric aspects related to radioiodine therapy after thyroidectomy in patients with thyroid cancer. The samples were studied with 50 patients undergoing treatment, by assessing the exposures of workers (nursing assistants, staff hygiene, medical and physical), the general public (accompanying and family members) and on the environment. To evaluate the workers, was made a survey of the environmental conditions of the room radioiodine and routines adopted by them during the treatment period. Estimating the dose equivalent per month for each employee, we observed that the maximum levels obtained for nursing assistants, the team of hygiene, medical and physicians were considered low in relation to the extent permitted by law. In order to assess the public, some situations have been suggested for the calculation of equivalent doses in which it was possible to verify the fundamental importance of isolating the patient in the 2 days first. Regarding the environment, the radioactive waste generated by patient had volume of 1.0 m3 and activity estimated at 0.91 mCi, taking a decay time for eliminating them about 75 days to reach the allowable value of 2 Ci / kg system of collecting garbage. Therefore, all radioactive waste removed from the patient's room should be sent to the warehouse for temporary storage of radioactive waste, located away from normal work areas

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Radiopharmaceuticals are substances marked with radionuclides that can be used for detection and treatment of cancer, infections and inflammatory diseases. They emit several types of radiation through different decay routes, each radioisotope with its specific properties and uses. They can usually be produced from several different materials, by bombardment with particle beams in a nuclear research reactor or cyclotron, depending on their characteristics. Brazil has four public institutions which produce - or import - and distribute radiopharmaceuticals to hospitals and clinics throughout its territory. The largest such institution, Ipen, distributes 97% of radiopharmaceuticals used in the country. Some radiopharmaceuticals decay very quickly, meaning they must be produced and quickly administered to the patient in the same location, presenting a logistical challenge. Nuclear medicine in Brazil is a promising field and has been steadily growing, although rigid laws and a lack of qualified work force hinder Research and Development efforts for new radiopharmaceuticals. The construction of a new nuclear research reactor, in 2016, should generate self-sufficiency and economy in radiopharmaceutical production and avoid a future crisis in the supply of technetium-99m, the most important radioisotope, used in over 80% of procedures with radiopharmaceuticals.

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Abstract Background In patients with advanced non-ischemic cardiomyopathy (NIC), right-sided cardiac disturbances has prognostic implications. Right coronary artery (RCA) flow pattern and flow reserve (CFR) are not well known in this setting. The purpose of this study was to assess, in human advanced NIC, the RCA phasic flow pattern and CFR, also under right-sided cardiac disturbances, and compare with left coronary circulation. As well as to investigate any correlation between the cardiac structural, mechanical and hemodynamic parameters with RCA phasic flow pattern or CFR. Methods Twenty four patients with dilated severe NIC were evaluated non-invasively, even by echocardiography, and also by cardiac catheterization, inclusive with Swan-Ganz catheter. Intracoronary Doppler (Flowire) data was obtained in RCA and left anterior descendent coronary artery (LAD) before and after adenosine. Resting RCA phasic pattern (diastolic/systolic) was compared between subgroups with and without pulmonary hypertension, and with and without right ventricular (RV) dysfunction; and also with LAD. RCA-CFR was compared with LAD, as well as in those subgroups. Pearson's correlation analysis was accomplished among echocardiographic (including LV fractional shortening, mass index, end systolic wall stress) more hemodynamic parameters with RCA phasic flow pattern or RCA-CFR. Results LV fractional shortening and end diastolic diameter were 15.3 3.5 % and 69.4 12.2 mm. Resting RCA phasic pattern had no difference comparing subgroups with vs. without pulmonary hypertension (1.45 vs. 1.29, p = NS) either with vs. without RV dysfunction (1.47 vs. 1.23, p = NS); RCA vs. LAD was 1.35 vs. 2.85 (p < 0.001). It had no significant correlation among any cardiac mechanical or hemodynamic parameter with RCA-CFR or RCA flow pattern. RCA-CFR had no difference compared with LAD (3.38 vs. 3.34, p = NS), as well as in pulmonary hypertension (3.09 vs. 3.10, p = NS) either in RV dysfunction (3.06 vs. 3.22, p = NS) subgroups. Conclusion In patients with chronic advanced NIC, RCA phasic flow pattern has a mild diastolic predominance, less marked than in LAD, with no effects from pulmonary artery hypertension or RV dysfunction. There is no significant correlation between any cardiac mechanical-structural or hemodynamic parameter with RCA-CFR or RCA phasic flow pattern. RCA flow reserve is still similar to LAD, independently of those right-sided cardiac disturbances.

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Micelles composed of amphiphilic copolymers linked to a radioactive element are used in nuclear medicine predominantly as a diagnostic application. A relevant advantage of polymeric micelles in aqueous solution is their resulting particle size, which can vary from 10 to 100 nm in diameter. In this review, polymeric micelles labeled with radioisotopes including technetium (99mTc) and indium (111In), and their clinical applications for several diagnostic techniques, such as single photon emission computed tomography (SPECT), gamma-scintigraphy, and nuclear magnetic resonance (NMR), were discussed. Also, micelle use primarily for the diagnosis of lymphatic ducts and sentinel lymph nodes received special attention. Notably, the employment of these diagnostic techniques can be considered a significant tool for functionally exploring body systems as well as investigating molecular pathways involved in the disease process. The use of molecular modeling methodologies and computer-aided drug design strategies can also yield valuable information for the rational design and development of novel radiopharmaceuticals.

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Untersuchungen zur stereokontrollierten Synthese von 3-Mercaptolysinderivaten: 3-Mercaptolysin und Peptide mit einer 3-Mercaptolysin-Einheit sind als Liganden fr Nukleardiagnostika in der Kontrastmittelforschung von groem Interesse. Fr das Screening Gewebe-selektiver Diagnostika sollten Mercaptolysinderivate, die sich fr den Einbau in Peptide eignen, stereokontrolliert aufgebaut werden. Als Grundlage wurde im Rahmen dieser Arbeit eine sehr effiziente Synthese von Methoxymethyl-(4-oxo-butyl)-carbaminsure-tert-butylester aus Pent-4-en-1-ol entwickelt. Nach Olefinierung des Aldehyds konnten Auxiliar-substituierte 6-Amino-hexensure-derivate in guten Ausbeuten erhalten werden. Diese bildeten die Startmaterialien fr auxiliargesteuerte Aziridinierungen mit anschlieender Ringffnung durch Schwefel-Nukleophile. Zudem wurden Azidierungen an Auxiliar-bewehrten Substraten, Michael-Additionen von Schwefel-Nukleophilen an Dehydroaminosuren und viele weitere Reaktionen untersucht. Es galt dabei auf patentrechtlich geschtzte Reaktionen zu verzichten, weil die Produkte ggf. in groem Mastab kommerziell genutzt werden sollen. Dabei konnten alle vier stereoisomeren 2-Acetylamino-6-(tert-butoxycarbonyl-methoxymethyl-amino)-3-(4-methoxy-benzylsulfanyl)-hexansurementhylester in guter Ausbeute synthetisiert werden. Nach Herstellung grerer Mengen der entsprechenden am Schwefelatom ungeschtzten N-Fmoc-Aminosurederivate sollen alle vier Stereoisomere in Peptide eingebaut und auf ihre Eignung als Liganden in Nukleardiagnostika untersucht werden. Untersuchungen zur Synthese neuartiger Ansa-Steroide: ber die Synthese von Ansa-Seco-Steroiden mittels eine Kaskade von intermolekularer Diels-Alder-Reaktion und anschlieender Retro-Diels-Alder-Reaktion an 5,6,7,8-Tetradehydrosteroiden wurde erstmals 1986 von E. Winterfeldt et al. berichtet. Die damit erffnete Mglichkeit eines vllig neuen Zugangs zu pharmakologisch interessanten Makrolid-Substraten konnte aber bislang nicht effektiv genutzt werden, weil insbesondere im Zusammenhang mit der Diels-Alder-Reaktion erhebliche prparative Probleme auftraten: Brauchbare Reaktivitt nur bei sehr wenigen Dienophilen, Regioselektivittsprobleme, etc. Hier galt es zu untersuchen, inwiefern sich diese Probleme durch die intramolekulare Reaktionsfhrung der Cycloaddition unterdrcken lassen knnen. Fr die intramolekulare Diels-Alder-Reaktion zwischen der 5,7-Dien-Einheit des Steroids und einer an das Substrat gebundenen Dienophil-Einheit ist die Mglichkeit einer gnstigen Anordnung der beiden Reaktanden-Gruppen entscheidend. Dafr wurden umfangreiche Untersuchungen zur alpha-konfigurierten Anbindung eines Dienophils in die 3-Position an 3-Hydroxy-5,6,7,8-Tetradehydrosteroiden durchgefhrt: Mitsunobu-Reaktionen, Oxidations-Reduktions-Sequenzen, Oxidations-Ketalisierungs-Sequenzen, etc. Hierbei wurden zahlreiche neue Steroide synthetisiert. Es gelang jedoch nicht, 5,6,7,8-Tetradehydrosteroide mit axial in Position 3 eingebundenen Dienophilen in prparativ nutzbaren Mengen zu synthetisieren. Bei der Untersuchung intermolekularer Diels-Alder-Reaktionen zwischen Ergosterol und Brommaleinsureanhydrid wurde vorzugsweise die Bildung der Addukte des 7,8,14,15-Tetradehydroisomers des Ergosterols beobachtet.

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Radiometals play an important role in nuclear medicine as involved in diagnostic or therapeutic agents. In the present work the radiochemical aspects of production and processing of very promising radiometals of the third group of the periodic table, namely radiogallium and radiolanthanides are investigated. The 68Ge/68Ga generator (68Ge, T = 270.8 d) provides a cyclotron-independent source of positron-emitting 68Ga (T = 68 min), which can be used for coordinative labelling. However, for labelling of biomolecules via bifunctional chelators, particularly if legal aspects of production of radiopharmaceuticals are considered, 68Ga(III) as eluted initially needs to be pre-concentrated and purified. The first experimental chapter describes a system for simple and efficient handling of the 68Ge/68Ga generator eluates with a cation-exchange micro-chromatography column as the main component. Chemical purification and volume concentration of 68Ga(III) are carried out in hydrochloric acid acetone media. Finally, generator produced 68Ga(III) is obtained with an excellent radiochemical and chemical purity in a minimised volume in a form applicable directly for the synthesis of 68Ga-labelled radiopharmaceuticals. For labelling with 68Ga(III), somatostatin analogue DOTA-octreotides (DOTATOC, DOTANOC) are used. 68Ga-DOTATOC and 68Ga-DOTANOC were successfully used to diagnose human somatostatin receptor-expressing tumours with PET/CT. Additionally, the proposed method was adapted for purification and medical utilisation of the cyclotron produced SPECT gallium radionuclide 67Ga(III). Second experimental chapter discusses a diagnostic radiolanthanide 140Nd, produced by irradiation of macro amounts of natural CeO2 and Pr2O3 in natCe(3He,xn)140Nd and 141Pr(p,2n)140Nd nuclear reactions, respectively. With this produced and processed 140Nd an efficient 140Nd/140Pr radionuclide generator system has been developed and evaluated. The principle of radiochemical separation of the mother and daughter radiolanthanides is based on physical-chemical transitions (hot-atom effects) of 140Pr following the electron capture process of 140Nd. The mother radionuclide 140Nd(III) is quantitatively absorbed on a solid phase matrix in the chemical form of 140Nd-DOTA-conjugated complexes, while daughter nuclide 140Pr is generated in an ionic species. With a very high elution yield and satisfactory chemical and radiolytical stability the system could able to provide the short-lived positron-emitting radiolanthanide 140Pr for PET investigations. In the third experimental chapter, analogously to physical-chemical transitions after the radioactive decay of 140Nd in 140Pr-DOTA, the rapture of the chemical bond between a radiolanthanide and the DOTA ligand, after the thermal neutron capture reaction (Szilard-Chalmers effect) was evaluated for production of the relevant radiolanthanides with high specific activity at TRIGA II Mainz nuclear reactor. The physical-chemical model was developed and first quantitative data are presented. As an example, 166Ho could be produced with a specific activity higher than its limiting value for TRIGA II Mainz, namely about 2 GBq/mg versus 0.9 GBq/mg. While free 166Ho(III) is produced in situ, it is not forming a 166Ho-DOTA complex and therefore can be separated from the inactive 165Ho-DOTA material. The analysis of the experimental data shows that radionuclides with half-life T < 64 h can be produced on TRIGA II Mainz nuclear reactor, with specific activity higher than any available at irradiation of simple targets e.g. oxides.

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In this work, the well-known MC code FLUKA was used to simulate the GE PETrace cyclotron (16.5 MeV) installed at S. Orsola-Malpighi University Hospital (Bologna, IT) and routinely used in the production of positron emitting radionuclides. Simulations yielded estimates of various quantities of interest, including: the effective dose distribution around the equipment; the effective number of neutron produced per incident proton and their spectral distribution; the activation of the structure of the cyclotron and the vault walls; the activation of the ambient air, in particular the production of 41Ar, the assessment of the saturation yield of radionuclides used in nuclear medicine. The simulations were validated against experimental measurements in terms of physical and transport parameters to be used at the energy range of interest in the medical field. The validated model was also extensively used in several practical applications uncluding the direct cyclotron production of non-standard radionuclides such as 99mTc, the production of medical radionuclides at TRIUMF (Vancouver, CA) TR13 cyclotron (13 MeV), the complete design of the new PET facility of Sacro Cuore Don Calabria Hospital (Negrar, IT), including the ACSI TR19 (19 MeV) cyclotron, the dose field around the energy selection system (degrader) of a proton therapy cyclotron, the design of plug-doors for a new cyclotron facility, in which a 70 MeV cyclotron will be installed, and the partial decommissioning of a PET facility, including the replacement of a Scanditronix MC17 cyclotron with a new TR19 cyclotron.

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Nuclear medicine imaging techniques such as PET are of increasing relevance in pharmaceutical research being valuable (pre)clinical tools to non-invasively assess drug performance in vivo. Therapeutic drugs, e.g. chemotherapeutics, often suffer from a poor balance between their efficacy and toxicity. Here, polymer based drug delivery systems can modulate the pharmacokinetics of low Mw therapeutics (prolonging blood circulation time, reducing toxic side effects, increasing target site accumulation) and therefore leading to a more efficient therapy. In this regard, poly-N-(2-hydroxypropyl)-methacrylamide (HPMA) constitutes a promising biocompatible polymer. Towards the further development of these structures, non-invasive PET imaging allows insight into structure-property relationships in vivo. This performant tool can guide design optimization towards more effective drug delivery. Hence, versatile radiolabeling strategies need to be developed and establishing 18F- as well as 131I-labeling of diverse HPMA architectures forms the basis for short- as well as long-term in vivo evaluations. By means of the prosthetic group [18F]FETos, 18F-labeling of distinct HPMA polymer architectures (homopolymers, amphiphilic copolymers as well as block copolymers) was successfully accomplished enabling their systematic evaluation in tumor bearing rats. These investigations revealed pronounced differences depending on individual polymer characteristics (molecular weight, amphiphilicity due to incorporated hydrophobic laurylmethacrylate (LMA) segments, architecture) as well as on the studied tumor model. Polymers showed higher uptake for up to 4 h p.i. into Walker 256 tumors vs. AT1 tumors (correlating to a higher cellular uptake in vitro). Highest tumor concentrations were found for amphiphilic HPMA-ran-LMA copolymers in comparison to homopolymers and block copolymers. Notably, the random LMA copolymer P4* (Mw=55 kDa, 25% LMA) exhibited most promising in vivo behavior such as highest blood retention as well as tumor uptake. Further studies concentrated on the influence of PEGylation (stealth effect) in terms of improving drug delivery properties of defined polymeric micelles. Here, [18F]fluoroethylation of distinct PEGylated block copolymers (0%, 1%, 5%, 7%, 11% of incorporated PEG2kDa) enabled to systematically study the impact of PEG incorporation ratio and respective architecture on the in vivo performance. Most strikingly, higher PEG content caused prolonged blood circulation as well as a linear increase in tumor uptake (Walker 256 carcinoma). Due to the structural diversity of potential polymeric carrier systems, further versatile 18F-labeling strategies are needed. Therefore, a prosthetic 18F-labeling approach based on the Cu(I)-catalyzed click reaction was established for HPMA-based polymers, providing incorporation of fluorine-18 under mild conditions and in high yields. On this basis, a preliminary PET study of a HPMA-based polymer radiolabeled via the prosthetic group [18F]F-PEG3-N3 was successfully accomplished. By revealing early pharmacokinetics, 18F-labeling enables to time-efficiently assess the potential of HPMA polymers for efficient drug delivery. Yet, investigating the long-term fate is essential, especially regarding prolonged circulation properties and passive tumor accumulation (EPR effect). Therefore, radiolabeling of diverse HPMA copolymers with the longer-lived isotope iodine-131 was accomplished enabling in vivo evaluation of copolymer P4* over several days. In this study, tumor retention of 131I-P4* could be demonstrated at least over 48h with concurrent blood clearance thereby confirming promising tumor targeting properties of amphiphilic HPMA copolymer systems based on the EPR effect.

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Die Nuklearmedizin ist ein modernes und effektives Werkzeug zur Erkennung und Behandlung von onkologischen Erkrankungen. Molekulare Bildgebung, die auf dem Einsatz von Radiopharmaka basiert, beinhaltet die Einzel-Photonen-Emissions-Tomographie (SPECT) und Positronenemissionstomographie (PET) und ermglicht die nicht-invasive Visualisierung von Tumoren auf nano-und picomolarer Ebene.rnDerzeit werden viele neue Tracer fr die genauere Lokalisierung von kleinen Tumoren und Metastasen eingefhrt und hinsichtlich ihrer Eignung untersucht. Die meisten von ihnen sind Protein-basierte Biomolekle, die die Natur selbst als Antigene fr die Tumorzellen produziert. Dabei spielen Antikrper und Antikrper-Fragmente eine wichtige Rolle in der Tumor-Diagnostik und Behandlung. Die PET-Bildgebung mit Antikrpern und Antikrperfragmenten bezeichnet man als immuno-PET. Ein wichtiger Aspekt hierbei ist, dass entsprechende Radiopharmaka bentigt werden, deren Halbwertszeit mit der Halbwertszeit der Biomolekle korreliert ist.rnIn neueren Arbeiten wird 90Nb als potenzieller Kandidat fr die Anwendung in der immuno-PET vorgeschlagen. Seine Halbwertszeit von 14,6 Stunden ist geeignet fr die Anwendung mit Antikrperfragmenten und einige intakten Antikrpern. 90Nb hat eine relativ hohen Anteil an Positronenemission von 53% und eine optimale Energie fr die +-Emission von 0,35 MeV, die sowohl eine hohe Qualitt der Bildgebung als auch eine niedrige Aktivittsmenge des Radionuklids ermglicht.rnErsten grundlegende Untersuchungen zeigten: i) dass 90Nb in ausreichender Menge und Reinheit durch Protonen-Bombardierung des natrlichen Zirkonium Targets produziert, ii) aus dem Targetmaterial in entsprechender radiochemischer Reinheit isoliert und iii) zur Markierung des monoklonalen Antikrpers (Rituximab) verwendet werden kann und iv) dieser 90Nb-markierte mAb eine hohe in vitro Stabilitt besitzt. Desweiteren wurde eine alternative und schnelle Abtrennungsmethode entwickelt, die es erlaubt 90Nb, mit einer geeigneten radiochemischen und radionuklidischen Reinheit fr eine anschlieende Markierung von Biomoleklen in einer Stunde zu aufzureinigen. Schlielich wurden erstmals 90Nb-markierte Biomoleklen in vivo untersucht. Desweiteren wurden auch Experimente durchgefhrt, um den optimalen bifunktionellen Chelatbildner (BFC) fr 90Niob zu finden. Mehrere BFC wurden hinsichtlich Komplexbildung mit NbV untersucht. Desferrioxamin (Df) erwies sich als geeignetster Chelator fr 90Nb. Der monoklonale Antikrper Bevacizumab (Avastin) wurde mit 90Nb markiert und eine Biodistributionsstudie und eine PET-Untersuchung durchgefhrt. Alle diese Ergebnisse zeigten, dass 90Nb ein vielversprechendes Radionuklid fr die Immuno-PET ist, welches sogar fr weitere kommerzielle Anwendungen in der klinischen Routine geeignet zu sein scheint.rn