Geerd-J. Meyer

Uptake of 11C-L- and D-methionine in brain tumors

Abstract11C-labeled l-and d-methionine uptake was measured in seven patients with brain tumors using positron emission tomography. Tumors accumulated both isomers of the tracer. The strongest uptake occurred in tumors with a high grade of malignancy, while low grade tumors accumulated less activity. The l to d uptake ratio in tumor regions ranged from 0.92–1.25. Conventional 99mTc-DTPA scans revealed blood-brain barrier damage in two patients with no or only slight 11C-methionine accumulation, while one patient with a negative 99mTc-DTPA scan accumulated 11C-methionine in the tumor region. In view of the biochemical pathway of methionine and the present findings, it is concluded that the uptake reflects metabolic activity in brain tissue rather than uptake by diffusion due to disruption of the blood-brain barrier.

Quantitative determination of regional extravascular lung water and regional blood volume in congestive heart failure

Regional extravascular lung water (rELW) and blood volume (rBV) in five controls and 14 patients with congestive heart failure (CHF) were measured by constant infusion of H215O and inhalation of 11CO using positron emission tomography (PET). The analysis of 18 regions per patient revealed a relatively homogenous level of rELW in the controls (x=0.11±0.02 g/cc; range, 0.08–0.21), whereas this increased in patients with CHF (0.17±0.02 g/cc; range, 0.10–0.51). The rBV was 0.21±0.02 g/cc in the controls and 0.17±0.02 g/cc in patients with CHF. A good correlation was found between the severity of chronic heart failure (according to the grading of the New York Heart Association) and mean extravascular lung water (ELW) (r=0.69), as well as between CHF and the ratio rELW/rBV (r=0.87); however, the correlation to hemodynamic data was less satisfactory (cardiac index, r=0.45; pulmonary capillary wedge pressure, r=0.47; ejection fraction, r=0.60). In supine controls, a progressive decrease in regional blood volume from the basal to the apical regions was observed, whereas the differences in ELW were only small. In patients with chronic heart failure, ELW in the basal parts was markedly increased, whereas in the apical regions, only minor deviations from the controls were observed. In the basal regions of these patients, the blood volume was reduced by about 30%. Instead of the normal basoapical gradient of blood volume, these patients showed a rather flat distribution. Radiographic findings of pulmonary edema generally appeared together with an ELW level of greater than 0.14 g/cc. We conclude that the amount and distribution of fluid in pulmonary congestion can be noninvasively assessed by PET.

The stability of 2-[18F]fluoro-deoxy-d-glucose towards epimerisation under alkaline conditions

Abstract Alkaline hydrolysis of 1,3,4,6-tetraacetyl-2-[ 18 F]fluoro-deoxy- d -glucose in the course of 2-[ 18 F]fluoro-deoxy- d -glucose ( 18 FDG) synthesis offers special advantages over acidic hydrolytic procedures, because the reaction time is short and thermal requirements are very mild. In view of the possible epimerization of 2-[ 18 F]fluoro-deoxy- d -glucose a multi-centre study has been performed to check the safety of this method for routine production of 18 FDG in view of the quality standards set by the European Pharmacopoeia. The study revealed that in using 0.33 M NaOH for the hydrolysis, a limitation of the reaction temperature to 40°C and a restriction of the reaction time to 5 min represent reaction conditions, which reliably limit the epimerization of 18 FDG to 18 FDM to 0.5%. Regarding the quality requirements on FDG as set forth by pharmacopoeial standards, alkaline hydrolysis of the intermediate in routine 18 FDG production is a safe and efficient reaction pathway, which furthermore obviates the requirement to check for other 2-substituted deoxy- d -glucose derivatives.

Approaches to Quantitative Analysis of Amino Acid Transport and Metabolism

Unlike in the case of glucose utilization, there is an ongoing debate on which kinetic model might be best suitable for the description of amino acid metabolism, in order to facilitate a quantitative interpretation of the PET data obtained from the applications of amino acids. Although these PET data have been obtained mostly from investigations of tumors, basic questions on the uptake processes in normal brain can be addressed, using these data sets, by analyzing reference regions and non-tumorous brain areas. Some protocols have been especially designed to establish a quantitative model for protein synthesis in normal brain and to increase the knowledge about the transport mechanisms.

Synthesis of 11C-labeled 5-hydroxytryptamine for the measurement of pulmonary endothelial cell function

Abstract [ 11 C]3-β-Aminoethyl-5-hydroxy-indole labeled in the β position of the ethyl group ([ 11 C]5-hydroxytryptamine, ([ 11 C]-5-HT), [ 11 C]serotonin) was synthesized from hydrogen [ 11 C]cyanide in a three-step procedure: [ 11 C]cyanide was first added to the cold precursor 5-methoxygramine methylsulfate by a phase-transfer catalyst supported nucleophilic substitution to give [ 11 C]5-methoxy-3-acetonitrile-indole; secondly, the methoxy group was cleaved with boron tribromide to give [ 11 C]5-hydroxy-3-acetonitrile-indole; thirdly, the nitrile was reduced to give [ 11 C]5-HT which was finally purified by reverse phase high pressure liquid chromatography. The overall radiochemical yield was 13%. 410 ± 140 MBq of [ 11 C]5-HT (sp. act. 5.1 GBq/μmol, radiochemical purity >96%) were ready for injection after the 78 min procedure.

Routine production of [13N]NH3 for PET examinations with a continuous flow water target

Abstract A continuous flow water target for [ 13 N]ammonia production has been designed. The target is in use since 1990 and up to now 140 irradiations (19 MeV protons, 10 μA, 15 min) have been performed with batches of about 2.56 GBq at EOS (end of synthesis) for PET examinations. Besides evaluation of nuclear parameters, target design, irradiation conditions and yield some attention is paid to radioactive contaminants.

The Use and Registration of PET-Radiopharmaceuticals

The development of regulatory schemes, for the production of PET radiopharmaceuticals can be understood only, in view of the development of PET as a new diagnostic tool. It seems at the moment that PET starts to cross the border from a research tool to a ma! clinical utility. Although some extreme expectations of the expansion have not been fulfilled in the last two years, the steady increase in PET investments is a strong indicator for its success. However, the increasing availability in the USA, as well as in Japan and especially in Germany was not matched by regulatory actions, to back up the legal foundations for its clinical use. Reasons for the hampered development have been identified as being regulatory deficits, educational deficits, and struggles between interest groups, as well as the complexity of the method itself.

Gradient effects in extravascular water determination using 15O-labelled water under steady state conditions: theory and error sensitivity

Steady state tracer measurements with short-lived isotopes allow the determination of dynamic and static physiological functions and parameters. Both types of measurements are affected by the gradient effects which result from the decay of the tracer through the volume observed. Using 15O-labelled compounds and positron emission tomography (PET), dynamic functions like flow are quite sensitive to variations in extraction fraction and distribution coefficient. In the operational equation for the determination of distribution volumes the gradient effect can be reduced to correction terms which are governed by the mean transit time of the tracer through the observed volume. Because mean transit times can be measured independently they allow a reasonable correction of gradient effects in distribution volume determinations, even if deviations of extraction fraction and distribution coefficient from unity must be considered.