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PubMed2005

Highlights of the Annual Congress of the European Association of Nuclear Medicine, Helsinki 2004, and a dash of horizon scanning.

The Annual Congress of the European Association of Nuclear Medicine represents the major scientific and professional event in the field of nuclear medicine in Europe. Specialists from all allied professions meet to discuss the latest findings and discoveries. A very large industrial exhibition demonstrates the latest technological innovations and developments. This Highlights Lecture summarises the scientific and medical advances discussed at this important gathering. The lecture covers a significant proportion of the data presented and/or discussed in up-to-date reviews, and places some of the trends encountered in the context of the evolution of the field as a whole. There is much food for thought in most areas of nuclear medicine: advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in known areas of clinical application such as neurology and psychiatry, cardiology, oncology, endocrine disorders, paediatrics, nephro-urology and musculoskeletal disorders. This Highlights Lecture is, however, only a brief resume of the vast amount of data discussed, which can be found in much greater detail in the Congress Proceedings, published as volume 31, supplement 2 of Eur J Nucl Med Mol Imaging in August 2004.

Nuclear Medicine↗

PubMed2007

Highlights of the European Association of Nuclear Medicine Congress, Athens, Greece, 30 September to 4 October 2006.

The 2006 EANM Congress, held in Athens, Greece, was once again a major event in the nuclear medicine scientific and educational calendar. The scientific programme, which included the second biennial ISRTRD meeting, confirmed the major developments taking place in (1) the diagnostic and prognostic uses of nuclear medicine imaging (both in PET and in single-photon studies), (2) radionuclide therapies, (3) radiochemistry and radiopharmacy, and (4) physics. This paper outlines the major findings in each of these areas.

Clinical Trials as Topic↗

PubMed2006

Highlights of the Annual Congress of the European Association of Nuclear Medicine, Istanbul, 2005: The incremental value of nuclear medicine for patient management and care.

The 2005 Annual Congress of the European Association of Nuclear Medicine (EANM) took place in Istanbul on October 15-19, under the chairmanship of Professor Hatice Durak. The programme was of excellent quality and represented a further step towards the achievement of a standardized EANM congress structure. A large industrial exhibition demonstrated the latest technological innovations and developments within the field. The congress was a great success: there were more than 4,000 participants, and 1,670 abstracts were received. Of these, 1,399 were accepted for oral or poster presentations, with a rejection rate of 16.2%. The original investigations presented were related to different areas of nuclear medicine, and addressed particularly advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in well-established areas of clinical application, such as oncology, cardiology, neurology, psychiatry, endocrinology, paediatrics, nephrology, and infection and inflammation. It is noteworthy that a number of studies presented at this congress focussed on the quantitative interpretation of the imaging data and on pragmatic endpoints, such as adverse outcomes, and identified when nuclear medicine procedures achieved clinical effectiveness for patient care and management. These and many other studies presented at the congress demonstrate once more the crucial role that nuclear medicine has to play in contemporary medicine. This highlights lecture is only a brief summary of the large amount of data presented and discussed, which can be found in much greater detail in the congress proceedings book, published as volume 32, supplement 1 of the Eur J Nucl Med Mol Imaging in September 2005.

Biomedical Research↗

PubMed2001

Imaging infection/inflammation in the new millennium.

In the closing half of the past century a wide variety of approaches were developed to visualise infection and inflammation by gamma scintigraphy. Use of autologous leucocytes, labelled with indium-111 or technetium-99m, is still considered the "gold standard" nuclear medicine technique for the imaging of infection and inflammation. However, the range of radiopharmaceuticals used to investigate infectious and non-microbial inflammatory disorders is expanding rapidly. Developments in protein/peptide chemistry and in radiochemistry should lead to agents with very high specific activities. Recently, positron emission tomography with fluorine-18 fluorodeoxyglucose has been shown to delineate infectious and inflammatory foci with high sensitivity. The third millennium will witness a gradual shift from basic (non-specific) or cumbersome, even hazardous techniques (radiolabelled leucocytes) to more sophisticated approaches. Here a survey is presented of the different approaches in use or under investigation.

Animals↗

PubMed2005

The usefulness of radiotracers to make the body biochemically transparent.

Radioactive isotopes are uniquely applicable to observe reactions or circuits of reactions at the molecular level without disturbing the system being studied. The advent of molecular imaging modalities, particularly positron emission tomography (PET), is a major breakthrough for the visualisation and quantitative assessment of cellular and molecular processes occurring in living tissues. The recent development of animal PET scanners that offers 2-mm resolution and is tailored to laboratory rodent models, has made a further great impact on in vivo biochemistry. With these live-imaging modalities at hand, radiotracer-based technologies allow to look directly at biochemical distribution and interaction processes. Tremendous progress made in radiotracer chemistry, primarily in carbon-11 and fluorine-18 radiochemistry, and in the design of imaging devices strengthens the usefulness of radiotracers in nuclear medicine and drug research and development and opens exciting opportunities for new applications, e.g., in food science.

Animals↗

PubMed2005

Synthesis and biodistribution of an 18F-labelled resveratrol derivative for small animal positron emission tomography.

Resveratrol (3,4',5-trihydroxy-trans-stilbene) is a naturally occurring phytoalexin and polyphenol existing in grapes and various other plants, and one of the best known 'nutriceuticals'. It shows a multiplicity of beneficial biological effects, particularly, by attenuating atherogenic, inflammatory, and carcinogenic processes. However, despite convincing evidence from experimental and clinical studies, data concerning the role of resveratrol and other members of the large polyphenols family for human health is still a matter of debate. One reason for this is the lack of suitable sensitive and specific methods, which would allow direct assessment of biodistribution, biokinetics, and the metabolic fate of these compounds in vivo. The unique features of positron emission tomography (PET) as a non-invasive in vivo imaging methodology in combination with suitable PET radiotracers have great promise to assess quantitative information on physiological effects of polyphenols in vivo. Herein we describe the radiosynthesis of an (18)F-labelled resveratrol derivative, 3,5-dihydroxy-4'-[(18)F]fluoro-trans-stilbene ([(18)F]-1), using the Horner-Wadsworth-Emmons reaction as a novel radiolabelling technique in PET radiochemistry for subsequent functional imaging of polyphenol metabolism in vivo. In a typical "three-step/one-pot" reaction, (18)F-labelled resveratrol derivative [(18)F]-1 could be synthesized within 120-130 min including HPLC separation at a specific radioactivity of about 90 GBq/mumol. The radiochemical yield was about 9% (decay-corrected) related to [(18)F]fluoride and the radiochemical purity exceeded 97%. First radiopharmacological evaluation included measurement of biodistribution ex vivo and positron emission tomography (PET) studies in vivo after intravenous application of [(18)F]-1 in male Wistar rats using a dedicated small animal PET camera with very high spatial resolution. Concordantly with data on bioavailability and metabolism of native resveratrol from the literature, these investigations revealed an extensive uptake and metabolism in the liver and kidney, respectively, of [(18)F]-1. This study represents the first investigation of polyphenols in vivo by means of PET.

Animals↗

PubMed2005

Small animal positron emission tomography in food sciences.

Positron emission tomography (PET) is a 3-dimensional imaging technique that has undergone tremendous developments during the last decade. Non-invasive tracing of molecular pathways in vivo is the key capability of PET. It has become an important tool in the diagnosis of human diseases as well as in biomedical and pharmaceutical research. In contrast to other imaging modalities, radiotracer concentrations can be determined quantitatively. By application of appropriate tracer kinetic models, the rate constants of numerous different biological processes can be determined. Rapid progress in PET radiochemistry has significantly increased the number of biologically important molecules labelled with PET nuclides to target a broader range of physiologic, metabolic, and molecular pathways. Progress in PET physics and technology strongly contributed to better scanners and image processing. In this context, dedicated high resolution scanners for dynamic PET studies in small laboratory animals are now available. These developments represent the driving force for the expansion of PET methodology into new areas of life sciences including food sciences. Small animal PET has a high potential to depict physiologic processes like absorption, distribution, metabolism, elimination and interactions of biologically significant substances, including nutrients, 'nutriceuticals', functional food ingredients, and foodborne toxicants. Based on present data, potential applications of small animal PET in food sciences are discussed.

Animal Nutritional Physiological Phenomena↗

PubMed1976

Automatic treatment of assay data by competitive protein binding and radioimmunoassay.

A method is devised for the automatic computation of data obtained from a series of determinations by radioimmunoassay or by competitive protein binding. The input data is introduced by means of an automatic paper tape punch attached to the sample counter. A series of programs is set up for a Hewlett Packard computer, model 2116B with 16K, which calculates bound and free fractions with control processes for varying possible errors. From experimental data, by linear least squares regression, a standard curve of best fit is derived and is considered in three different ways. The curve of best fit is selected by comparing the correlation coefficients obtained and by calculating the unknown sample concentrations. The program presents the results graphically together with a list of results which is for use within the Radiochemistry laboratory. Individual reports are also prepared for sending to those departments that requested the test.

Binding, Competitive↗

PubMed1982

Cyclotron production of 128Cs (3.62 min). A new positron-emitting radionuclide for medical applications.

The cyclotron production of the short-lived positron emitter 128Cs (3.62 min) from its longer-lived parent 128Ba (2.42 d), based upon the 133Cs(p, 6n) 128Ba leads to 128Cs reaction (Q = -43.98 MeV), has been studied. Cesium-128 has potential applications in positron tomography, particularly for imaging the myocardium and/or for the assessment of regional blood flow. Thick-target yields (mCi/muAh) and cross sections (mb) for 128Ba, 131Ba, 129Cs and 132Cs were measured in the 67-36 MeV proton-energy region. Cyclotron production of 128Ba-128Cs (transient equilibrium) was measured as 3.1 mCi/muAh at end of bombardment (EOB) with a 2.32 g cm-2 thick CsCl target with a proton entrance energy of 67 MeV and exit energy of 54 MeV. Target-radiochemistry using ion-exchange methods allow the preparation of a generator-type system from which high-radionuclidic purity, radiopharmaceutical quality, no-carrier-added 128Cs can be obtained for immediate administration. In addition, with proper radiochemical handling of the 128Ba-128Cs generator, no-carrier-added, high-purity 129Cs (32.35 h, 372 keV, 32%) can also be produced for use in research applications.

Cesium Radioisotopes↗

PubMed1982

Determination of Co, Cu, Fe, Hg, Mn, Sb, Se and Zn in milk samples.

Concentrations of Co, Cu, Fe, Hg, Mn, Sb, Se and Zn in IAEA milk (dry) standard A-11 were re-evaluated with the help of instrumental and radiochemical neutron activation analysis (NAA). The results show reasonably good agreement for Co (5.1 +/- 0.55 ng/g) and Zn (34 +/- 2.5 micrograms/g), in relation to the recommended values. For Cu (374 +/- 15 ng/g), Fe (2.4 +/- 0.34 microgram/g) and Mn (250 +/- 20 ng/g); the results obtained are lower than the reported values. Cu, Mn, and Zn were cross-checked by atomic absorption spectrophotometry (AAS). The results, Cu = 331 +/- 27 ng/g, Mn = 302 +/- 62 ng/g, and Zn = 35 +/- 1 microgram/g, fall within the range of mean values obtained by NAA. for Hg and Se, using instrumental NAA, only upper limits could be indicated; because of the low levels of concentrations of Hg and Se on one hand, and high content of P (9100 micrograms/g) in A-11 milk standard on the other, NAA coupled with radiochemistry is to be preferred for these two elements. In pooled human milk, in addition to Cu and Mn (radiochemical) and Co, Fe, Sb and Zn (instrumental), Hg and Se could also be determined non-destructively because of the favorable Hg/P and Se/P ratios in this matrix.

Animals↗

PubMed1993

Measurements of the gastrointestinal absorption and tissue distribution of plutonium, americium and polonium in experimental animals.

In order to set limits on environmental and occupational intakes of radionuclides, information is needed on their uptake and metabolism in man. Human data are very limited, particularly for long-lived alpha-emitting isotopes such as those of the actinides. Animal experiments are therefore an important source of data on the distribution of radionuclides in tissues, and the effects of factors such as subject age and the chemical form of elements on gastrointestinal absorption. The NRPB performs experimental programs using mainly rats and guinea pigs. In order to study the gastrointestinal absorption and tissue distribution of plutonium, americium and polonium, a variety of analytical techniques are employed. These include ion exchange and solvent extraction leading to alpha spectrometry and liquid scintillation counting. The investigation of low specific-activity environmental or industrial materials, and the very low bioavailability of elements such as the actinides, means that very low levels of activity have to be measured. Contamination at the dissection and tissue separation stage, as well as during the radiochemistry, has to be rigorously avoided. Where very detailed information is needed on the location of radionuclides within tissues, such as in the study of alpha-emitter distribution in the intestine, autoradiography is used. The application and relevance of different measurement techniques to animal studies will be discussed and examples of the results presented.

Aging↗

PubMed1994

Recent developments in the radioimmunotherapy of cancer.

Recent trials using radiolabeled monoclonal antibodies, particularly for hematologic neoplasms, have demonstrated the ability of these agents to destroy tumor cells safely and specifically. Advances in molecular biology, immunology and radiochemistry will allow the continued development of strategies to overcome the remaining obstacles to effective therapy with radioimmunoconjugates.

Animals↗

PubMed2005

Optimisation study of alpha-cyclotron production of At-211/Po-211g for high-LET metabolic radiotherapy purposes.

The production of no-carrier-added (NCA) alpha-emitter (211)At/(211g)Po radionuclides for high-LET targeted radiotherapy and immunoradiotherapy, through the (209)Bi(alpha,2n) reaction, together with the required wet radiochemistry and radioanalytical quality controls carried out at LASA is described, through dedicated irradiation experiments at the MC-40 cyclotron of JRC-Ispra. The amount of both the gamma-emitter (210)At and its long half-lived alpha-emitting daughter (210)Po is optimised and minimised by appropriate choice of energy and energy loss of alpha particle beam. The measured excitation functions for production of the main radioisotopic impurity (210)At-->(210)Po are compared with theoretical predictions from model calculations performed at ENEA.

Astatine↗

PubMed2005

NCA nucleophilic radiofluorination on substituted benzaldehydes for the preparation of [18F]fluorinated aromatic amino acids.

Nucleophilic aromatic substitution is a challenging task in radiochemistry. Therefore, a thorough evaluation and optimisation of this step is needed to provide a satisfactory tool for the routine preparation of [(18)F]fluorinated aromatic amino acids. Two methods, already proposed elsewhere, were evaluated and improved. The yields for the radiofluorination were increased whereas activity loss during solid phase extraction was observed. Radiochemical yields for the two methods were 92.7+/-5.5% (method 1) and 92.1+/-12.3% (method 2) for conversion and 11.1+/-2.8% (method 1) and 34.8+/-0.6% (method 2) for purification, respectively. In total, we demonstrate an optimised method for the preparation of this important class of [(18)F]fluorinated synthons for PET.

Amino Acids, Aromatic↗

PubMed2005

Perfluorinated markers for hypoxia detection: synthesis of sulfur-containing precursors and [18F]-labelling.

Synthetic pathways of two novel sulfurated precursors for [18F]-labelling by oxidative fluorodesulfurization reaction are described. A three-step sequence starting from N-phthalimido-beta-alanine allows the preparation of a new trithioorthoester as valuable precursor of the synthesis of [18F]-3,3,3-trifluoropropylamine, a convenient radiolabelled intermediate for [18F]-EF3. A five-step sequence for the preparation of methyl 4-phthalimido-2,2-difluoropropanedithioate from ethyl 2,2-difluoropropanoate, via the key conversion step of alpha,alpha'-difluorothioamidate to the corresponding alpha,alpha'-difluorodithioester, and the first results of its use as precursor for oxidative fluorodesulfurization in [18F]-radiochemistry are also presented.

Fluorine Radioisotopes↗

PubMed2006

Cure of incurable lymphoma.

The most potent method for augmenting the cytocidal power of monoclonal antibody (MAb) treatment is to conjugate radionuclides to the MAb to deliver systemic radiotherapy (radioimmunotherapy; RIT). The antigen, MAb, and its epitope can make a difference in the performance of the drug. Additionally, the radionuclide, radiochemistry, chelator for radiometals and the linker between the MAb and chelator can have a major influence on the performance of drugs (radiopharmaceuticals) for RIT. Smaller radionuclide carriers, such as antibody fragments and mimics, and those used for pretargeting strategies, have been described and evaluated. All of these changes in the drugs and strategies for RIT have documented potential for improved performance and patient outcomes. RIT is a promising new therapy that should be incorporated into the management of patients with B-cell non-Hodgkin's lymphoma (NHL) soon after these patients have proven incurable. Predictable improvements using better drugs, strategies, and combinations with other drugs seem certain to make RIT integral to the management of patients with NHL, and likely lead to cure of currently incurable NHL.

Antibodies, Monoclonal↗

PubMed2005

Radioactivity in trinitite six decades later.

The first nuclear explosion test, named the Trinity test, was conducted on July 16, 1945 near Alamogordo, New Mexico. In the tremendous heat of the explosion, the radioactive debris fused with the local soil into a glassy material named Trinitite. Selected Trinitite samples from ground zero (GZ) of the test site were investigated in detail for radioactivity. The techniques used included alpha spectrometry, high-efficiency gamma-ray spectrometry, and low-background beta counting, following the radiochemistry for selected radionuclides. Specific activities were determined for fission products (90Sr, 137Cs), activation products (60Co, 133Ba, 152Eu, 154Eu, 238Pu, 241Pu), and the remnants of the nuclear fuel (239Pu, 240Pu). Additionally, specific activities of three natural radionuclides (40K, 232Th, 238U) and their progeny were measured. The determined specific activities of radionuclides and their relationships are interpreted in the context of the fission process, chemical behavior of the elements, as well as the nuclear explosion phenomenology.

New Mexico↗

PubMed2004

Quantitative imaging of Na/I symporter transgene expression using positron emission tomography in the living animal.

Transgene expression can be measured in living animals by positron emission tomography (PET) using reporter genes associated with radiolabeled substrates or ligands. We examined here whether PET images obtained with a new reporter gene system (sodium/iodide symporter (NIS) and [124I]iodide) could provide quantitative information on gene expression in mice. Mice received various doses of recombinant adenovirus in which the expression of the NIS cDNA was driven by the CMV promoter and subsequently [124I]iodide. Postmortem gamma counting of liver biopsies was correlated to the adenovirus dose and with NIS mRNA concentration. In addition, immunohistochemically NIS-positive cells increased with higher tissue activities. Finally, a linear relationship existed between the postmortem gamma counting in liver tissues and that calculated from images obtained through small animal PET scanning (r = 0.9581), although there was a bias at high and low specific values. This systematic study on 35 animals demonstrates that quantitative information on gene expression can be obtained from PET images using the NIS reporter system. This new methodology of quantitative imaging of gene expression presents the advantage of avoiding extensive radiochemistry, an important step for more disseminated use of this emerging technology. In addition, this work supports further development of the NIS system for noninvasive assessment of gene delivery in preclinical and clinical studies.

Adenoviridae↗