New Measurement of the 60Fe Half-Life.

We have made a new determination of the half-life of the radioactive isotope 60Fe using high precision measurements of the number of 60Fe atoms and their activity in a sample containing over 10(15) 60Fe atoms. Our new value for the half-life of 60Fe is (2.62+/-0.04) x 10(6) yr, significantly above the previously reported value of (1.49+/-0.27) x 10(6) yr. Our new measurement for the lifetime of 60Fe has significant implications for interpretations of galactic nucleosynthesis, for determinations of formation time scales of solids in the early Solar System, and for the interpretation of live 60Fe measurements from supernova-ejecta deposits on Earth.

Precision measurement of the 7Be(p,gamma)8B cross section with an implanted 7Be target.

The 7Be(p,gamma)8B reaction plays a central role in the evaluation of solar neutrino fluxes. We report on a new precision measurement of the cross section of this reaction, following our previous experiment with an implanted 7Be target, a raster-scanned beam, and the elimination of the backscattering loss. The new measurement incorporates a more abundant 7Be target and a number of improvements in design and procedure. The point at E(lab)=991 keV was measured several times under varying experimental conditions, yielding a value of S17(E(c.m.)=850 keV)=24.0+/-0.5 eV b. Measurements were carried out at lower energies as well. Because of the precise knowledge of the implanted 7Be density profile, it was possible to reconstitute both the off- and on-resonance parts of the cross section and to obtain from the entire set of measurements an extrapolated value of S17(0)=21.2+/-0.7 eV b.

Preparation of 124I solutions after thermodistillation of irradiated 124TeO2 targets.

The 4.15-d radionuclide 124I is produced via the nuclear reaction 124Te(d, 2n) 124I by irradiation of 96% enriched 124TeO2 with 14 MeV deuterons, followed by thermodistillation. In order to minimise the loss of 124I, the quartz distillation tube was fitted to a stainless steel helix capillary trap directly behind the end of the furnace. Using this device, distillation yields of more than 80% were routinely obtained, and the activity was concentrated in markedly less than 100 microL solution. The 124I produced by this method proved to be useful for labelling proteins and IUdR.

Imaging brain tumor proliferative activity with [124I]iododeoxyuridine.

Iododeoxyuridine (IUdR) uptake and retention was imaged by positron emission tomography (PET) at 0-48 min and 24 h after administration of 28.0-64.4 MBq (0.76-1.74 mCi) of [124I]IUdR in 20 patients with brain tumors, including meningiomas and gliomas. The PET images were directly compared with gadolinium contrast-enhanced or T2-weighted magnetic resonance images. Estimates for IUdR-DNA incorporation in tumor tissue (Ki) required pharmacokinetic modeling and fitting of the 0-48 min dynamically acquired data to correct the 24-h image data for residual, nonincorporated radioactivity that did not clear from the tissue during the 24-h period after IUdR injection. Standard uptake values (SUVs) and tumor:brain activity ratios (Tm:Br) were also calculated from the 24-h image data. The Ki, SUV, and Tm/Br values were related to tumor type and grade, tumor labeling index, and survival after the PET scan. The plasma half-life of [124I]IUdR was short (2-3 min), and the arterial plasma input function was similar between patients (48 +/- 12 SUV*min). Plasma clearance of the major radiolabeled metabolite ([124I]iodide) varied somewhat between patients and was markedly prolonged in one patient with renal insufficiency. It was apparent from our analysis that a sizable fraction (15-93%) of residual nonincorporated radioactivity (largely [124I]iodide) remained in the tumors after the 24-h washout period, and this fraction varied between the different tumor groups. Because the SUV and Tm:Br ratio values reflect both IUdR-DNA incorporated and exchangeable nonincorporated radioactivity, any residual nonincorporated radioactivity will amplify their values and distort their significance and interpretation. This was particularly apparent in the meningioma and glioblastoma multiforme groups of tumors. Mean tumor Ki values ranged between 0.5 +/- 0.9 (meningiomas) and 3.9 +/- 2.3 microl/min/g (peak value for glioblastoma multiforme, GBM). Comparable SUV and Tm:Br values at 24 h ranged from 0.13 +/- 0.03 to 0.29 +/- 0.19 and from 2.0 +/- 0.6 to 6.1 +/- 1.5 for meningiomas and peak GBMs, respectively. Thus, the range of values was much greater for Ki (approximately 8-fold) compared with that for SUV (approximately 2.2-fold) and Tm:Br (approximately 3-fold). The expected relationships between Ki, SUV, and Tm:Br and other measures of tumor proliferation (tumor type and grade, labeling index, and patient survival) were observed. However, greater image specificity and significance of the SUV and Tm:Br values would be obtained by achieving greater washout and clearance of the exchangeable fraction of residual (background) radioactivity in the tumors, i.e., by increased hydration and urinary clearance and possibly by imaging later than 24 h after [124I]IUdR administration.

[76Br]Bromodeoxyuridine, a potential tracer for the measurement of cell proliferation by positron emission tomography, in vitro and in vivo studies in mice.

5-Bromo-2'-deoxyuridine (BrUdR) labeled with 77Br and 76Br was compared with 5-iodo-2'-deoxyuridine (IUdR) labeled with 125I or 131I, first in vitro then in in vivo experiments in mice. The results showed a significantly higher incorporation of BrUdR into DNA than IUdR, which can be explained by the greater similarity (size and surface hydrophilicity of the molecules) of BrUdR to thymidine. Both tracers are dehalogenated quickly in vivo but not in vitro. Free bromide is excreted more slowly than iodide, resulting in a higher background activity level after the application of [76Br]BrUdR and compensates for the favorable DNA incorporation. 76Br has more favorable properties than 124I for imaging purposes with positron emission tomography (PET) because of a very convenient half-life (16 h vs. 4.15 days) and about double the positron yield per decay. However, the more favorable physical properties are balanced by the slower excretion and thus the estimated radiation dose is higher in the case of 76Br than 124I. Thus, both tracers, [124I]IUdR and [76Br]BrUdR are potentially suitable but not optimal to measure cell proliferation in vivo. The difference between the two tracers is small and the extrapolation from mice to human difficult, and thus it cannot be concluded if one of the tracers would be better than the other for imaging of cancer patients.

Radiosynthesis and quality assurance of 5-[124I]Iodo-2'-deoxyuridine for functional PET imaging of cell proliferation.

5-[124I]Iodo-2'-deoxyuridine ([124I]IUdR) was routinely produced by direct electrophilic labelling of 2'-deoxyuridine with 124I of high specific activity (12 Ci/micromol) in an Iodogen-coated ReactiVial, followed by purification on a Sep-Pak C-18 cartridge. The radiochemical purity was determined by TLC on a Silicagel-60 plate and by reverse-phase HPLC on a RP-18 column. Based upon 45 syntheses, the yield ranged from 45% to 65%. The radiochemical impurity of [124I]IUdR was determined at 2.9% by TLC (mainly iodate) and 4.3% by HPLC. The chemical stability of the solvated formulation allowed a time window of 2 days following end of synthesis (EOS) for chemical application, based upon the required 95% radiochemical purity grade of [124I]IUdR. The labelled compound was routinely used for the clinical determination of cell proliferation in glioma patients by positron emission tomography.

Auger-electron spectra of radionuclides for therapy and diagnostics.

The present paper documents the calculation of radiation spectra and of radial dose distribution around a point source for 24 selected radionuclides. The radionuclides were ordered into three groups: Nuclides potentially useful for therapy by emission of Auger electrons: 51Cr, 64Cu, 67Ga, 73Se, 75Se, 77Br, 80mBr, 94Tc, 99mTc, 114mIn, 115mIn, 123I, 124I, 125I, 167Tm, 193mPt, and 195mPt, nuclides potentially useful for therapy by alpha-particles with additional emission of Auger electrons: 212Bi, 211At and 255Fm, and nuclides potentially useful for electron Auger-therapy with simultaneous PET diagnosis: 73Se, 94Tc and 124I. The calculations imply strongly the development of labelled DNA-seeking compounds useful as carrier for the Auger- and Coster-Kronig electron-emitting radionuclides.

COMT inhibitors and metabolism of fluorodopa enantiomers in aggregating cell cultures.

Organotypic primary cell cultures of fetal rat brain were used as a model system to study the effect of COMT inhibitors on the cerebral metabolic conversions of fluoro-DOPA enantiomers. The selective COMT inhibitors OR 486 and CGP 28014 were used in conjunction with 5F-L-DOPA, 6F-L-DOPA and 6F-D-DOPA as substrates. Methylation can be clearly reduced by application of OR 486 at nanomolar level, without inhibition of AADC and MAO. The uptake of the substrate is unchanged. CGP 28014, already known to be active only in vivo, has no influence on the metabolic conversion rates of the fluoro-DOPA isomers. These results show that use of this culture system allows statement concerning the in vitro activity of COMT inhibitors. It has not been possible to show an increase of absolute levels of decarboxylation products due to inhibition of COMT, however, but the reduction in levels of methylated product itself may have significance for PET studies of the human brain.

Savoxepine: striatal dopamine-D2 receptor occupancy in human volunteers measured using positron emission tomography (PET).

The extent and duration of striatal dopamine-D2 receptor occupancy by savoxepine in humans has been studied using positron emission tomography with [11C]-raclopride, in order to investigate why the anticipated favourable ratio between its extrapyramidal and antipsychotic effects was not achieved in practice. After 0.25 mg savoxepine, striatal D2 receptor occupancy peaked at 50-60% after 24-36 h and disappeared within 6 days. After doses of 0.1 mg to 0.5 mg, D2 receptor occupancy in the putamen and caudate nucleus increased from 20 to 70% 3-7 h after administration and amounted to 40 to 75% at the peak time (20-29 h). This suggests that cumulative D2 receptor blockade would occur if equal or increasing doses of savoxepine were given repeatedly. Extrapyramidal adverse-effects would be likely to occur under such circumstances. An adequate test of the theory that preference for hippocampal dopamine D2 receptors with afford a good therapeutic ratio requires an alternative dosing regimen.

Metabolism of 5-fluoro-dopa and 6-fluoro-dopa enantiomers in aggregating cell cultures of fetal rat brain.

The cerebral metabolism of enantiomers of 5-fluoro-DOPA (5F-DOPA) and 6-fluoro-DOPA (6F-DOPA) was characterized in organotypic cell cultures of fetal rat brain. This system permits the investigation of metabolic processes in brain tissue exclusively, without the effects of peripheral metabolism and transport. Metabolic profiles for each substrate were determined in comparison with those of L-DOPA and D-DOPA. The uptake of DOPA and fluoro-DOPA in aggregating brain cell cultures is strongly preferential for L-enantiomers. Decarboxylation by aromatic L-amino acid decarboxylase is an active step: the major products are dopamine (DA) or 6F-DA and their corresponding products of oxidative deamination, i.e. dihydroxyphenylacetic acid (DOPAC) or 6F-DOPAC, respectively. Decarboxylation products of D-enantiomers occur in lower amounts, and 5F-D-DOPA is not decarboxylated. However, 5F-DOPA is O-methylated to a great extent, and levels of 3-O-methyl-5F-DOPA are higher after incubation with 5F-D-DOPA than with 5F-L-DOPA. These data may serve as a support for more detailed modeling of [18F]F-DOPA metabolism than can be applied to the evaluation of the cerebral biochemistry of the DA system with positron emission tomography in vivo.

Comparative metabolism of fluorinated 3,4-dihydroxyphenylalanine isomers in aggregating brain cell cultures.

Fluorinated analogues of 3,4-dihydroxyphenylalanine (DOPA) were tested for intracellular metabolic conversion in aggregating cell cultures prepared from fetal rat brain. 5-Fluoro-D/L-DOPA was methylated almost exclusively to 3-O-methyl-5-fluoro-D/L-DOPA. Metabolism of 6-fluoro-D/L-DOPA resulted in 6-fluorodopamine, 6-fluoro-3,4-dihydroxyphenylacetic acid, and 3-O-methyl-6-fluoro-D/L-DOPA, but with a qualitatively and quantitatively different metabolite pattern compared with that of L-DOPA and D/L-DOPA, respectively. Homovanillic acid and fluorohomovanillic acid have not been found intracellularly in the cultures. On the basis of these data, the model development of the cerebral metabolism of tracers used in positron emission tomography can be improved.

Routine 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG) myocardial tomography using a normal large field of view gamma-camera.

There is a recent need to study glucose metabolism of the heart in ischemic, as well as in "hibernating or stunned" myocardium, and compare it with that in perfusion studies. In non-positron emission tomography centers, positron imaging is possible with a standard Anger-type camera if proper collimation and adequate shielding of the camera crystal can be achieved. For the study with fast-decaying isotopes, seven-pinhole tomography (7PHT), a limited-angle method designed for transaxial tomography of the left ventricle using a nonrotating camera, is well suited, because projections are acquired simultaneously. Individual adjustment (patient supine) of the camera's view axis (CAx) with the left ventricular axis (LVAx) gives excellent results: sensitivity for CHD 82%, specificity 72% in a prospective 201TI study (48 patients, x-ray coronarography as reference). Good alignment of CAx with LVAx is also achieved with the patient prone in LAO in a hammock above the camera surface. In this setting additional lead shielding of the camera is possible using a table reinforced with 5 cm of lead with a central hole for the 7PH-collimator, which has a special lead inlay. This allows utilization of the 511 KeV emitter 18F-FDG, which with a half-life of 109 minutes, can be transported a reasonable distance from the production site. System sensitivity and resolution for 18F was found comparable to 201Tl, 99mTc, and 123I using a phantom. First clinical examinations after 201Tl stress/redistribution studies showed increased 18F-FDG uptake in ischemic heart segments, as well as in "hibernating" nonperfused or "stunned" myocardium.

Production of 77Kr and 79Kr for medical applications via proton irradiation of bromine: excitation functions, yields and separation procedure.

Excitation functions were measured for the formation of both 77Kr and 79Kr by interaction of protons with bromine of natural isotopic composition. The theoretical yields are 62.8 mCi/muAh for 77Kr in the energy range from 45 to 32 MeV, with 1.5% 76Kr and 11.7% 79Kr impurities, and 14.9 mCi/muAh for 79Kr in the energy range of 45 to 0 MeV, respectively. The experimental yield after dry distillation separation of the krypton isotopes from irradiated NaBr targets, lies between 40 and 60% of the theoretical ones. Below the melting point of NaBr, krypton is released by diffusion, caused by lattice defects in the target material.