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PubMed2002

[The nuclear medicine department and the TEP/Biomedical Cyclotron unit].

During the last 25 years, the clinical and experimental activity in nuclear medicine at Erasme hospital has been influenced by the implementation of positron emission tomography (PET) in 1990 as a method of brain functional investigation. The activity of the PET/biomedical cyclotron unit has been dedicated to various subjects in neurology, neurosciences, psychiatry, oncology and cardiology. This has been made possible by developments in radiochemistry. The radiochemistry laboratory has designed and produced original tracers such as 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)-methyl]guanine (FHPG), a tracer of viral thymidine kinase activity in gene therapy protocols. We have brought new applications of PET, such as its integration into stereotactic neurosurgical and radioneurosurgical techniques in order to improve their diagnostic and therapeutic performance in neurooncology. We have also conducted multiple studies on brain physiology and pathophysiology, in particular with the use of functional and metabolic brain mapping methods and the use of tracers of neurotransmission systems. The Department of nuclear medicine has also performed studies on bone metabolism and investigated in vivo imaging methods of infectious and immune processes.

Belgium↗

PubMed1994

Positron emission tomography: physics, instrumentation, and image analysis.

Positron emission tomography (PET) is a noninvasive diagnostic technique that permits reconstruction of cross-sectional images of the human body which depict the biodistribution of PET tracer substances. A large variety of physiological PET tracers, mostly based on isotopes of carbon, nitrogen, oxygen, and fluorine is available and allows the in vivo investigation of organ perfusion, metabolic pathways and biomolecular processes in normal and diseased states. PET cameras utilize the physical characteristics of positron decay to derive quantitative measurements of tracer concentrations, a capability that has so far been elusive for conventional SPECT (single photon emission computed tomography) imaging techniques. Due to the short half lives of most PET isotopes, an on-site cyclotron and a radiochemistry unit are necessary to provide an adequate supply of PET tracers. While operating a PET center in the past was a complex procedure restricted to few academic centers with ample resources, PET technology has rapidly advanced in recent years and has entered the commercial nuclear medicine market. To date, the availability of compact cyclotrons with remote computer control, automated synthesis units for PET radiochemistry, high-performance PET cameras, and user-friendly analysis workstations permits installation of a clinical PET center within most nuclear medicine facilities. This review provides simple descriptions of important aspects concerning physics, instrumentation, and image analysis in PET imaging which should be understood by medical personnel involved in the clinical operation of a PET imaging center.

Energy Metabolism↗

PubMed1993

Impurities in the [18O]water target and their effect on the yield of an aromatic displacement reaction with [18F]fluoride.

Fluorine-18 in the form of fluoride ion has widespread utility in PET radiochemistry. This paper explores the effect of possible metal ion contamination of the water on the yield of the displacement of a nitro group off of dinitrobenzene by fluoride has been investigated as a model reaction for fluoride displacement. The metal ions were found to have a profound effect if they were at the level of the carbonate added to the synthetic procedure. The yields from the reaction are best fit by a model in which the metal ions complex the carbonate ion and thus reduce the pH which in turn reduces the efficiency of the reaction. The formation of [18F]fluoroacetate in the target was explored as a mode for making the fluoride in the target unreactive. It was found that essentially no fluoroacetate was formed under our irradiation conditions. The sources of carrier fluoride were examined. It was found that carrier fluoride was introduced during the transfer of water into and out of the target and not during the irradiation.

Fluorine Radioisotopes↗

PubMed1995

An industry survey of current lower limits of detection for various radionuclides.

The results of a survey to assess detection limits of various radionuclides and their associated costs is presented herein. Included among the radionuclides of interest are mixed fission products, mixed activation products, actinides and transuranics, plus tritium (3H) and 14C. The survey encompassed commercial analytical radiochemistry services and nuclear instrument suppliers in the United States. In the study, a simple soil sample was defined as the object of consideration with no requirements for any special quality control/assurance. Standard procedures and instrumentation were requested, as were standard prices/costs required for the various analyses. The minimum detectable level for most isotopes using standard procedures was on the order of 0.0037 to 0.037 Bq g-1 (0.1 to 1.0 pCi g-1). The analytical costs varied by factors of 2 to 4 over a range of 0.0037 to 0.37 Bq g-1 (0.1 to 10.0 pCi g-1). While the ability to detect below 0.0037 Bq g-1 (0.1 pCi g-1) is possible, the required detection times were considered prohibitive for a commercial laboratory.

Industry↗

PubMed1993

Innervation of the human adrenal cortex: simultaneous visualisation using acetylcholinesterase histochemistry and dopamine beta-hydroxylase immunohistochemistry.

The inter-relationship between putative cholinergic and noradrenergic innervation of the human adrenal cortex was investigated using a technique which combined acetylcholinesterase histochemistry, choline acetyltransferase radiochemistry and dopamine beta-hydroxylase immunohistochemistry. Cholinergic and noradrenergic nerve fibres had a near-identical distribution, with varicose noradrenergic fibres located immediately alongside non-varicose cholinergic nerve bundles in all cortical zones. Choline acetyltransferase activity was consistently detected in the adrenal cortex, confirming the presence of cholinergic neurons. It is postulated that noradrenergic innervation has a role in the modulation of cortical endocrine secretion, while cholinergic nerves are mainly concerned with the control of medullary secretion.

Acetylcholinesterase↗

PubMed1991

Status of the Positron Emission Tomography Centre at the Austin Hospital.

A Positron Emission Tomography (PET) Centre is currently being established at the Austin Hospital, Melbourne. The Centre has recently purchased a Siemens Model 951/31 PET scanner and an Ion Beam Applications (IBA) Model 10/5 cyclotron with associated targetry and automated radiochemistry modules. The initial areas of clinical investigation at the Austin Hospital will be heart and brain studies using 18Fluorodeoxyglucose (FDG) and 13Nitrogen-ammonia (13NH3). The heart studies will concentrate on determining myocardial viability in patients following infarction whilst studies of epileptic patients will involve determination of the epileptic focus in the brain. A description of the major technical instrumentation is given together with an overview of the radiopharmaceutical production processes and the initial program of clinical investigations to be undertaken.

Australia↗

PubMed1996

[Protein- and peptide-derived radiopharmaceuticals].

Recent development of radiochemistry has provided various reagent that allow stable attachment of radiolabels to proteins in vivo. The advent of genetic and protein engineering have generated proteins and peptides with reduced or no immunogenicity or more favorable distribution characteristics. However, localization of radioactivity in nontarget tissues still constitutes a problem to be resolved for accurate diagnosis and effective therapy using the radiopharmaceuticals. Recent studies have indicated that radiometabolites after lysosomal proteolysis of proteins play a critical role in the radioactivity levels in nontarget tissues. Furthermore, radiochemical design of polypeptides that liberates radiometabolites of rapid urinary excretion after lysosomal proteolysis in nontarget tissues has facilitated rapid radioactivity elimination from nontarget tissues to urine. From these findings, we believe a new era of protein- and peptide-derived radiopharmaceuticals much more suitable for diagnostic and therapeutic applications will be opened soon.

Animals↗

PubMed1994

Overview of clinical radioimmunodetection of human tumors.

The role of radioimmunodetection in the detection of cancer has been established through the development of high affinity immunoconjugates and recent improvements in radiochemistry. Advances in imaging techniques, particularly single-photon emission computed tomography and image registration, also have dramatically improved the sensitivity and accuracy of tumor detection. Molecular engineering of immune constructs provides promise of enhanced tumor localization properties and reduced immunogenicity, allowing repeated studies to be performed. The role of radioimmunodetection in the evaluation of cancer patients will increase in importance in the future.

Adult↗

PubMedDate not supplied

Absorption of labeled triethanolamine salicylate in human and canine knee joints. II.

The transdermal absorption by tissues of salicylate from triethanolamine salicylate (TEA/S) ointment applied to canine and human skin was shown to be consistent, significant, and reproducible. Salicylate levels were measured using thin-layer chromatography, nuclear magnetic resonance, and radiochemistry. Absorption was directly proportional to the concentrations of the active ingredient in the ointment up to the 10 per cent preparation. Tissue salicylate levels were not influenced by the sex of the canine subjects. In humans, the activity of the patients affected both tissue levels and urinary excretion. Autoradiographic and doubly labeled studies suggest that during transdermal absorption of TEA/S, the salt may disassociate; this could permit the salicylate to have a longer transit time in the area of application.

Animals↗

PubMed1996

Formulation development of an antifibrin monoclonal antibody radiopharmaceutical.

These studies have shown that formulation development of a monoclonal antibody radio-immunoscintigraphy agent is a challenging task involving a number of issues related to the radiochemistry of labeling as well as the stability of the antibody. Through a systematic approach, as described in this study, a stable and efficacious product of high quality can be developed in a rational and efficient manner. In developing an optimized formulation of Tc-99m-antifibrin Fab' for use in immunoscintigraphy of DVT, a number of critical components were examined in regard to technetium-labeling chemistry and the ability of the formulation to support the long-term stability of the product. It was found that the addition of glucarate as a transfer ligand, SnCl2 as a reducing agent, and neutral-to-acidic pH of the solution were essential for optimum radiolabeling of 0.5 mg of antifibrin Fab' to a desired activity of 25 mCi of Tc-99m. The lyophilization of the final product was also required to further stabilize both the antifibrin Fab' fragment and the reducing agent. The addition of carbohydrate as bulking agent and lyoprotectant and inclusion of EDTA as a chelating agent further improved the performance of the formulations, resulting in products with long shelf-life. Many of the principles described in this study are not only useful in developing a technetium-based immunoscintigraphic agent but are also applicable to other immunopharmaceuticals, including products involving delivery of radionuclides, drugs, and toxins for immunotherapy of cancer and other diseases.

Animals↗

PubMed2007

Micro-reactors for PET tracer labeling.

Miniaturization of PET radiosynthesis devices (micro-reactors or microfluidic systems) is an emerging area that has the potential to deliver many advantages, such as more efficient use of hot-cell space for production of multiple radiotracers; use of less non-radioactive precursor for saving precious material and a reduced separation challenge; highly controlled, reproducible and reliable radiotracer production; and cheap, interchangeable, disposable and quality-assured radiochemistry processors. Several 'proof of principle' examples along with basics of micro-reactor flow control, mixing principle and design, and device fabrication are discussed in this chapter.

Animals↗

PubMed2007

Fluorine-18 labeling of small molecules: the use of 18F-labeled aryl fluorides derived from no-carrier-added [18F]fluoride as labeling precursors.

The favourable long-half life, the ease of production and the low energy of the emitted positron make 18F an ideal radionuclide for PET imaging. Radiochemistry of 18F basically relies on two distinctive types of reactions: nucleophilic and electrophilic reactions. All syntheses of 18F-labeled radiotracers are based on either [18F]fluoride ion or [18F]fluorine gas as simple primary labeling precursors which are obtained directly from the cyclotron. They can be applied either directly to the radiosynthesis or they can be transformed into more complex labeling precursors enabling the multi-step build-up of organic tracer molecules. The topic of this review is a survey on the application of several 18F-labeled aryl fluorides as building blocks derived from no-carrier-added (n.c.a.) [18F] fluoride to build up small monomeric PET radiotracers at high specific radioactivity by multi-step synthesis procedures.

Animals↗

PubMed1984

Positron emission tomography.

One of the most exciting new techniques introduced in the last ten years is positron emission tomography (PET). PET provides quantitative, three-dimensional images for the study of specific biochemical and physiological processes in the human body. This approach is analogous to quantitative in vivo autoradiography but has the added advantage of permitting non-invasive in vivo studies. PET scanning requires a small cyclotron to produce short-lived positron emitting isotopes such as oxygen-15, carbon-11, nitrogen-13 and fluorine-18. Proper radiochemical facilities and advanced computer equipment are also needed. Most important, PET requires a multidisciplinary scientific team of physicists, radiochemists, mathematicians, biochemists and physicians. This review analyses the most recent trends in imaging technology, radiochemistry, methodology, and clinical applications of positron emission tomography.

Adolescent↗

PubMed2006

Evaluation of 99mTc labeled diadenosine tetraphosphate as an atherosclerotic plaque imaging agent in experimental models.

The potential of 99mTc labeled P1, P4-di (adenosine-5')-tetraphosphate (Ap4A) for imaging experimental atherosclerotic plaques was evaluated in New Zealand white (NZW) rabbits. To label the 99mTc to Ap4A, stannous tartrate solution was used. 99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of 99mTc-Ap4A were 85% to 91%. Biodistribution study revealed 99mTc-Ap4A cleared from blood rapidly. Thirty min after 99mTc-Ap4A administrated on NZW atherosclerotic rabbits, lesion to blood (target/blood, T/B) ratio was 3.17 +/- 1.27, and lesions to normal (target/non-target, T/NT) ratio was 5.23 +/- 1.87. Shadows of atherosclerotic plaques were clearly visible on radioautographic film. Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera images. Atherosclerotic abdominal aortas were clearly visible on in vivo images 15 min to 3 h after 99mTc-Ap4A administration. 99mTc-labeled Ap4A can be used for rapid noninvasive detection of experimental atherosclerotic plaque.

Animals↗

PubMed2005

[Positron emission tomography in neuroscience. An integrative part of clinical diagnostic methods and experimental research].

The role of molecular neuroimaging techniques is increasing in the understanding of pathophysiological mechanism of diseases. To date, positron emission tomography is the most powerful tool for the non-invasive study of biochemical and molecular processes in humans and animals in vivo. With the development in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analyzed by PET. This opens up the exciting and rapidly field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. Besides its usefulness for basic research positron emission tomography has been proven to be superior to conventional diagnostic methods in several clinical indications. This is illustrated by detection of biological or anatomic changes that cannot be demonstrated by computed tomography or magnetic resonance imaging, as well as even before symptoms are expressed. The present review summarizes the clinical use of positron emission tomography in neuroscience that has helped elucidate the pathophysiology of a number of diseases and has suggested strategies in the treatment of these patients. Special reference is given to the neurovascular, neurodegenerative and neurooncological disease.

Animals↗

PubMed2004

Assessment of drinking water radioactivity content by liquid scintillation counting: set up of high sensitivity and emergency procedures.

In our institute, different procedures have been developed to measure the radioactivity content of drinking water both in normal and in emergency situations, such as those arising from accidental and terrorist events. A single radiometric technique, namely low level liquid scintillation counting (LSC), has been used. In emergency situations a gross activity screening is carried out without any sample treatment by a single and quick liquid scintillation counting. Alpha and beta activities can be measured in more than one hundred samples per day with sensitivities of a few Bq/L. Higher sensitivity gross alpha and beta, uranium and radium measurements can be performed on water samples after specific sample treatments. The sequential method proposed is designed in such a way that the same water sample can be used in all the stages, with slight modifications. This sequential procedure was applied in a survey of the Lombardia district. At first tap waters of the 13 largest towns were examined, then a more detailed monitoring was carried out in the surroundings of Milano and Lodi towns. The high sensitivity method for the determination of uranium isotopes was used to check the presence of depleted uranium in Lake Garda. Reduced equipment requirements and relative readiness of radiochemical procedures make LSC an attractive technique which can also be applied by laboratories lacking specific radiochemistry facilities and experience.

Emergencies↗

PubMed2002

Fluorinated amino acids for tumour imaging with positron emission tomography.

The currently preferred radiopharmaceutical for positron emission tomography (PET) in oncology is 2-[(18)F]fluoro-deoxyglucose (FDG). Increased accumulation of this deoxyglucose analogue in tumour cells is based on elevated glucose metabolism by tumour cells and subsequent trapping in the cells. In the search for new PET tracers, amino acids have been widely studied. A new amino acid tracer should preferably have similar high uptake in tumour cells but low non-specific uptake in normal tissues and any pathology other than tumour. In recent years, several amino acids have been labelled with either gamma radiation-emitting radionuclides or positron-emitting radionuclides, the most commonly used being carbon-11. However, the longer half-life of fluorine-18 matches better with the relatively slow process of protein synthesis and also facilitates shipping of the radiolabelled amino acids to hospitals without an on-site cyclotron or dedicated radiochemistry laboratory. The number of fluorinated amino acids under investigation is increasing, and one of the major points of discussion is the underlying mechanism of the tumour visualisation. While it has been shown that some amino acids can be used to measure the protein synthesis rate, others are used with the sole aim of measuring the rate of uptake into the cell. The differences between measuring amino acid transport (rate) and protein synthesis rate with (18)F-labelled amino acids are discussed.

Amino Acids↗

PubMed2003

PET-based molecular imaging in neuroscience.

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.

Alzheimer Disease↗