18F Activity Research Articles

Organ-specific dietary fatty acid uptake in humans using positron emission tomography coupled to computed tomography

A noninvasive method to determine postprandial fatty acid tissue partition may elucidate the link between excess dietary fat and type 2 diabetes. We hypothesized that the positron-emitting fatty acid analog 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid ((18)FTHA) administered orally during a meal would be incorporated into chylomicron triglycerides, allowing determination of interorgan dietary fatty acid uptake. We administered (18)FTHA orally at the beginning of a standard liquid meal ingested in nine healthy men. There was no significant (18)FTHA uptake in the portal vein and the liver during the 1st hour. Whole body PET/CT acquisition revealed early appearance of (18)FTHA in the distal thoracic duct, reaching a peak at time 240 min. (18)FTHA mean standard uptake value increased progressively in the liver, heart, quadriceps, and subcutaneous and visceral adipose tissues between time 60 and 240 min. Most circulating (18)F activity between time 0 and 360 min was recovered into chylomicron triglycerides. Using Triton WR-1339 treatment in rats that received (18)FTHA by gavage, we confirmed that >90% of this tracer reached the circulation as triglycerides. This novel noninvasive method to determine tissue dietary fatty acid distribution in humans should prove useful in the study of the mechanisms leading to lipotoxicity.

Improving Lung Scintigraphy

1919 Objectives Investigate the feasibility of D- and L-enantiomers of [18F]-labelled 2- and 6-FDOPA for melanoma imaging. Methods D- and L-enantiomers of [18F]2- and 6-FDOPA were prepared by the direct fluorination of DOPA. 20 mBq of each tracer (0.2 mL) was injected into the tail veins of mice bearing B16-F10 mealnoma tumor after they were anesthetized with isoflurane. Animals were imaged using a Philips Mosaic small animal PET scanner followed by the CT component of a SPECT/CT scanner for co-registration. B16-F10 melanoma cells, grown in complete MEM/F11 medium, were incubated with 55 mBq of [18F]2- and 6-FDOPA (D- and L-) for 120 min at 37 oC. Following centrifugation, cells were separated from the culture medium and thoroughly washed with HBSS buffer until less than 10% of the total 18F remained in the supernatant. Percent uptake of FDOPA isomers in tumor cells was calculated based on the 18F activity measured in each component. Results Fluorine-18 uptake in the tumor cells for 2-F-L-DOPA (20.5%) was considerably higher compared to 2-F-D-DOPA (7.9%). Itwas comparable between 6-F-D-DOPA (17%) and 6-F-L-DOPA (19%). PET images of B16-F10 melanoma bearing mice showed clear delineation of the tumor 120 min after injection with [18F] labelled 6-F-D-DOPA and 2-F-L-DOPA. Conclusions Both [18F] labelled 6-D-DOPA and 2-F-L-DOPA appeared to be promising tracers for the delineation of melanoma. [18F]6-F-D-DOPA may not be metabolised in vivo causing a higher signal to noise ratio in tumor images. Relaitively higher upatke of [18F]2-F-L-DOPA may be due its incorporation into melanin by the Raper-Mason Scheme for melanogenesis. Research Support Authors acknowledge Dr. Karen Gulenchyn and Ms. Carol Dunne of HHS for their support.

SU‐FF‐I‐78: Effective Doses in Whole Body and Brain PET/CT Procedures of Adult Patients

Purpose: To determine the variation in patient effective doses for whole body and brain PET‐CT procedures and determine methods for dose optimization. Method and Materials: Demographic data (age, gender, and weight), CT exposure parameters and activity of 18F (FDG) were taken from patient records of 543 whole body and initial 54 brain PET/CT cases. PET Effective doses were estimated using the dose conversion coefficients for 18F (FDG) in ICRP Report No. 80. CT effective doses for the manufacturer's stated CTDIair were estimated using the IMPACT dose calculator. The Pearson correlation (p <0.0001) of PET effective doses with weight, age and 18F (FDG) activity was analyzed. Results: There are more male patients (55% and 61%) than females (45% and 39%) for whole body and brain procedures respectively. The mean age of patients for whole body is 47 ±18 years old and 34 ±16 years old for brain studies. The mean 18F (FDG) for whole body is 460 ± 130 MBq and 410 ± 45 Mbq for brain procedures. Pooling all ages, the mean effective doses are 8 ± 2 mSv and 10 ± 1mSv for whole body and brain respectively and dose correlate poorly with weight, age and activity. CT effective doses are in the range of 11 to 15 Msv. Conclusion: There is a wide variation in the 18F(FDG) activity which is about 30% of the mean activity. Standardization of activity can be formulated per weight or per age and a study of the setting image quality criteria and using low dose CT should be made. A dose conversion coefficient of 1.8 Msv per Gy can be used for whole body CT using 6 and 9 mGy CTDI to estimate effective dose.

Factors affecting the specific activity of [18F]fluoride from a [18O]water target

Characterisation of the influence of different polymeric tube materials of a water target system, used for the production of 18F activity, on the specific activity of radiotracers. Target water samples taken from different locations of the 18F water target system of a Cyclone 18/9 cyclotron, equipped with Teflon (PTFE) or polypropylene (PP) tubes, were analyzed for non-radioactive [19F]fluoride content. [19F]Fluoride content was measured by ion chromatography (IC20, Dinoex) with suppressed conductivity detection. Both the ion chromatographic results and the amount of 18F activity produced were used for the calculation of the specific activity (SA) of [18F]fluoride at the start of the labelling synthesis. To check these results, the SA of the labelled receptor ligand [18F]ZK811460 was also determined by using the different tubing materials. Dose-exposed PTFE tubes of the target dispensing (loading) system were identified to be a major source of [19F]fluoride contamination. By replacing PTFE tubes of the target dispensing system with PP tubes, the content of 19F was reduced considerably resulting in an increase of SA of the radiotracer [18F]ZK811460 by factor of two.

18F-FDG metabolism in a rat model of chronic infarction

Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p < 0.05) that persisted throughout the study. Semiquantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p < 0.001). The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.

Assessment of 18F PET signals for automatic target volume definition in radiotherapy treatment planning

Introduction Positron emission tomography (PET) alone or in combination with computer tomography (PET/CT) is increasingly used in target volume assessment. A standardized way of converting PET signals into target volumes is not available at present. Materials and methods Assuming a uniform signal emission from a tumour and surrounding normal tissues, a model-based method was developed to determine a relative threshold level (Th rel) for gross tumour volume delineation. Two phantoms consisting of cylindrical and spherical sources of diameter ranging from 4.5 to 43 mm in a tank and 18F activities ranging from 0.001 to 0.15 MBq/ml for tank and sources, respectively, were used for PET/CT imaging. A Th rel was calculated that best corresponded to the physical diameter of the cylindrical sources. Software (SW) was generated to automatically delineate volumes based on this threshold. The SW was validated for in vitro and in vivo PET signals. Results The Th rel best representing the source diameter was 41 ± 2.5% (95% confidence level) of the background-subtracted signal. The mean deviation for sources of diameter ⩾12.5 mm was ⩽1.5 mm. The Th rel was constant for diameters ⩾12.5 mm. For source diameters <12.5 mm, the 41% level over-estimated the real source diameter by a factor depending on the diameter. In an in vitro set-up the SW was capable of segmenting solitary PET volumes to within 1.4 mm (1SD). For non-homogeneous signals in a clinical set-up minimal manual intervention is presently required to separate target from non-target signals. The SW may slightly underestimate target volumes when compared with CT-based volumes, but works well as a first approximation. The volume can be manually adapted to give the ultimate target volume. Conclusions SW-based automatic delineation of the volume of 18F activity is feasible and highly reproducible. Volumes can be subsequently modified by the clinician if necessary. This approach will increase the efficiency of the planning process.

The Effect of Insulin on the Intracellular Distribution of 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic Acid in Rats

The aim of this study was to determine the effect of hyperinsulinemia on myocardial and hepatic distribution and metabolism of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA). Mitochondrial retention and intracellular lipid incorporation of [18F]FTHA were compared to that of [14C]-2-bromopalmitate or [14C]palmitate during hyperinsulinemic clamp vs. saline infusion in male Wistar rats. Mitochondrial 18F activity was increased in the heart (1.7 +/- 0.4 vs. 0.5 +/- 0.1% ID/g, P < 0.05), whereas it was reduced in the liver (1.1 +/- 0.3 vs. 1.8 +/- 0.4% ID/g, P < 0.05) during insulin vs. saline infusion, respectively. Mitochondrial [14C]-2-bromopalmitate activity was affected by insulin in a similar way in both tissues. The fractional esterification of [18F]FTHA into triglycerides was impaired compared to [14C]palmitate in both tissues, and [18F]FTHA was insensitive to the shift of esterification of fatty acids into complex lipids in response to insulin. [18F]FTHA is sensitive to insulin-induced modifications of free fatty acid oxidative metabolism in rats but is insensitive to changes in nonoxidative fatty acid metabolism.

Accuracy of cardiac PET imaging using post-injection transmission scan

The purpose of this study was to investigate the accuracy of cardiac PET with post-injection transmission scans. We performed a phantom study using 18F solution as well as 13N-ammonia PET study of ten patients. The average activities of no myocardial defect phantom model were estimated, and myocardial defect sizes of 12 phantom models were measured by pre- and post-injection transmission methods at various 18F activities. In 13N-ammonia PET at rest and during adenosine triphosphate (ATP) stress studies, measured defect sizes were compared between both methods. The ratios of average activity estimated by both methods (post/pre value) were almost 1.00 at each 18F activity and segment. Measured defect sizes by both methods showed an excellent correlation with true defect sizes (r = 0.98, p < 0.01 for pre vs. true value: r = 0.98, p < 0.01 for post vs. true value). The mean absolute errors of measurements were minimal up to 3.5% LV, and were similar between both methods. In 13N-ammonia PET, measured defect sizes by both methods also showed a good correlation (r = 0.97, p < 0.01). The results indicate that cardiac PET imaging with post-injection transmission scan provides information on myocardial tracer activity as well as myocardial defect size as does conventional pre-injection transmission method.

Comparisons CCRI(II)-K3.F-18 and APMP.RI(II)-K3.F-18 of activity measurements of the radionuclide 18F and links to the key comparison reference value of the BIPM.RI(II)-K1.F-18 comparison

In 2003, the CCRI(II) decided that an indirect comparison of 18F measurements piloted by the National Physical Laboratory (NPL), UK in 2001 was sufficiently well constructed that it could be converted into a CCRI(II) comparison, with comparison identifier CCRI(II)-K3.F-18. At the same time, the pilot laboratory made a bilateral comparison with the institute in Chinese Taipei, comparison identifier APMP.RI(II)-K3.F-18. The results of the comparisons have been reported and the key comparison working group (KCWG) of the CCRI(II) has approved the mechanism to link all the results to the key comparison reference value (KCRV) of 18F. The KCRV has been determined through the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.F-18. These comparisons have enabled a further four results to be added to the matrix of degrees of equivalence for 18F activity measurements.Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

Electrochemical transfer of [18F]fluoride from [18O]water into organic solvents ready for labeling reactions

For labeling reactions [18F]fluoride has to be separated from [18O]water and transferred into an organic solvent suitable for nucleophilic substitutions. An electrolytical method is described for depositing [18F]fluoride on a vitreous carbon electrode and releasing it directly into CH3CN or DMSO. In the presence of Et3N×3HF, [18F]fluoride is almost quantitatively released into acetonitrile. When using n.c.a conditions, i.e., Et3N.HCl, desorption of the 18F activity is almost 70% and 60% in acetonitrile and DMSO, respectively, already within 5 minutes.

Production of a high purity [formula omitted] radioactive beam

An efficient method for the production and post-acceleration of a pure 18F(T1/2=109.8min) radioactive beam has been developed. Large amounts of 18F are produced via the 18O(p,n)18F reaction using a 15.5MeV proton beam on an 18O-enriched water target. After the chemical purification of the target content, the 18F activity is transferred into [18F]-fluoromethane. It is then transported to an ECR ion source, where after dissociation of the molecules, the fluorine atoms are ionized. Finally, the 18F2+ ions are accelerated to 14MeV in a second cyclotron. The different steps in the production cycle and the characteristics of the final 18F beam are discussed.

Chemical reactivity of the 18F electrophilic reagents from the 18O( p, n) 18F gas target systems

A comprehensive evaluation of the reactivity of 18F electrophilic fluorinating agents derived from the 18O( p, n) 18F reaction conducted in target bodies made of aluminum, silver, copper, nickel, and gold-plated copper is reported. Two representative electrophilic reactions, namely addition across a double bond and substitution on an aromatic ring (fluorodemercuration and fluorodestannylation), were tested with the 18F activity generated in the [ 18O]O 2 target systems. Identical reactions were also conducted with analogous nonradioactive fluorinating agents as control experiments. The products of all these reactions were analyzed by NMR spectroscopy. Results of these experiments clearly showed that 18F activities recovered from aluminum, silver, and copper target bodies were better suited for radiochemical syntheses, irrespective of the irradiation protocols employed. The 18F activity from a gold-plated target was suitable only for addition reactions. Further, the fluorodemercuration reaction essentially failed with the single-step irradiation technique conducted in nickel and gold-plated targets. In contrast, the fluorodestannylation reaction was quite successful with the 18F reagents recovered from all the target bodies and irradiation protocols.

Production of [ 18F]F 2 using the 16O( 3He,p) 18F reaction

For the first time, the 16O( 3He,p) 18F reaction has been used for the production of 18F electrophilic reagents. The predominant reactive chemical specie recovered in the single-step postirradiation gases was [ 18F]F 2. Decay curve and Ge(Li) analyses established the main radionuclidic impurities in this nuclear reaction as 11C and 15O. Recovery of the 18F activity was exceptionally high, approaching 90% using an electroformed nickel target body. Consistent 18F recoveries for this nuclear reaction (~70%) were realized with a novel aluminum target body. The utility of the [ 18F]F 2 recovered from this oxygen gas target system in radiopharmaceutical preparations is demonstrated by the successful synthesis of 6-[ 18F]fluoro- l-dopa (11.0 mCi at EOB) via a fluorodemercuration method.

Proton irradiation of [ 18O]O 2: Production of [ 18F]F 2 and [ 18F]F 2 + [ 18F]OF 2

The production of 18F electrophilic reagents via the 18O(p,n) 18F reaction has been investigated in small-volume target bodies made of aluminum, copper, gold-plated copper and nickel, having straight or conical bore shapes. Three irradiation protocols—single-step, two-step and modified two-step—were used for the recovery of the 18F activity. The single-step irradiation protocol was tested in all the target bodies. Based on the single-step performance, aluminum targets were utilized extensively in the investigation of the two-step and modified two-step irradiation protocols. With an 11-MeV cyclotron and using the two-step irradiation protocol, >1Ci [ 18F]F 2 was recovered reproducibly from an aluminum target body. Probable radical mechanisms for the formation of OF 2 and FONO 2 (fluorine nitrate) in the single-step and modified two-step targets are proposed based on the amount of ozone generated and the nitrogen impurity present in the target gases, respectively.

Metals suitable for fluorine gas target bodies: First use of aluminum for the production of [ 18F]F 2

A comprehensive evaluation of different metals (aluminum, silver, copper, nickel, and gold-plated copper) was undertaken for the fabrication of target bodies with straight and conical bore shapes for the production of [ 18F]F 2 via the 20Ne(d,α) 18F nuclear reaction. Of these metals, aluminum, silver and copper have never been used for the production of [ 18F]F 2. All these target bodies were easily passivated using a mild beam-induced plasma technique in the presence of 1% F 2 in neon or argon. The recovery of 18F activity was higher with electroformed nickel and silver bodies, probably due to favorable thermal conductivities. Aluminum proved to be a useful material for fluorine gas targets. The consistent recovery of 18F activities, ease and low cost of manufacturing and low nuclear activation properties all make aluminum an ideal choice for fluorine gas targetry. To our knowledge, this investigation is the first to highlight the use of aluminum as a target body material for the routine production of [ 18F]F 2. A reasonable mechanism based on the Langmuir-Rideal surface atom recombination is also proposed for the behavior of [ 18F]F 2 recovery from a nickel target body.

Synthesis and organ distribution of [ 18F]fluoro-org 6141 in the rat: A potential glucocorticoid receptor ligand for positron emission tomography

For the synthesis of [ 18F]Fluoro-Org 6141 via a nucleophilic substitution reaction with 18F −, the tosyl group was chosen as the leaving group because of its stability and excellent leaving group ability. The biodistribution of the high affinity and moderate lipophilicity (log P = 2.66, calculated value) ligand [ 18F]Fluoro-Org 6141 (specific activity 8.2 to 37 TBq/mmol, yield 10% at EOB) was examined in sham adrenalectomized (sADX) and adrenalectomized (ADX) male Wistar rats. Two days after ADX or sADX, the animals were anesthetized and 0.37 to 1.85 MBq of [ 18F]Fluoro-Org 6141 was administered intravenously. Kinetics of 18F activity uptake were monitored for 3 h using a stationary double-headed positron emission tomography (PET) camera, and the biodistribution was assessed by ex vivo determination of radioactivity in several tissues and different brain areas. One hour after injection of the radioligand, the bladder, kidney, liver, trachea, and bone of sADX animals contained more concentration on a wet weight basis than blood. Three hours post injection, radioactivity was retained in bladder, trachea, and bone. The accumulation of radioactivity in brain corresponded to the concentration of activity in the blood within the first hours after injection. ADX animals showed a higher uptake of 18F activity in spleen, testes, and brain areas (hippocampus and brainstem) but a lower uptake in bone than sADX rats. PET scans suggested that 18F activity uptake in the brain had not yet reached a maximum at this interval. Although [ 18F]Fluoro-Org 6141 is not useful for PET studies of glucocorticoid receptors (GRs), the results obtained with this compound indicate a synthetic strategy suitable for the synthesis of high-affinity radioligands for GRs.

Positron emission tomography with 18F-DOPA: Interpretation and biological correlates in nonhuman primates

Positron emission tomography (PET) was carried out, with 18F-DOPA as a ligand, in normal control monkeys and “parkinsonian” monkeys who had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The following approaches were used in data analysis: ratio of 18F accumulation in specific to nonspecific brain areas and 18F-DOPA influx constant obtained using either the actual plasma 18F-DOPA or the 18F activity in a nonspecific brain area as the input function. The results from these analyses were compared to one another and to biological parameters relevant to dopaminergic function. The striatum/cortex ratio and the rate constant calculated from plasma 18F-DOPA appeared to be the most sensitive analytic techniques.

Determination of oxygen in high purity gallium by using charged particle activation analysis

The determination of the oxygen content in high purity gallium was performed by 18F producing 3He induced nuclear reactions. The 16O(3He, p)18F and 16O(3He, n)18Ne18F reactions were chosen taking into account their 10 considerable cross section and the half-life of the produced positron emitter isotope. The samples were prepared under nitrogen atmosphere to avoid further oxidation. 6.5 MeV 3He beam was used for irradiation with a beam current of less than 100 nA. To avoid melting the samples were frozen during the irradiation. A well defined surface layer of the activated samples was removed, and the 511 keV annihilation radiation was measured by HpGe gamma-spectrometry. Half-life measurement was also applied to separate the 18F activity from the produced other positron emitter isotopes. The oxygen concentration of the samples was between 5 and 100 μg/g.

Regional myocardial perfusion and glucose metabolism in experimental left bundle branch block.

Several authors have reported cases in which 201Tl scintigraphy demonstrated perfusion abnormality in the septum of patients with left bundle branch block (LBBB) and normal coronary arteriogram. The mechanism of this abnormality, however, remains to be clarified. To determine whether LBBB itself induces abnormal myocardial perfusion and ischemia and to elucidate its mechanism, we used an in vivo animal model. LBBB was induced by right ventricular pacing in 17 open-chest dogs. We examined myocardial perfusion and glucose uptake using 201Tl and 18F-labeled 2-fluoro-2-deoxy-D-glucose. 201Tl activity in the septum was reduced to 74.7 +/- 14.5% of its maximal activity, and mean activity was 86.5 +/- 5.3% in the free wall (p less than 0.05). 18F activity in the septum was also reduced compared with that in the free wall (67.4 +/- 12.1% versus 88.0 +/- 5.2%, p less than 0.05). Regional myocardial blood flow was significantly reduced in the septum compared with the free wall, averaging 0.53 +/- 0.18 ml/min/g versus 0.84 +/- 0.14 ml/min/g, respectively (p less than 0.01). Systolic thickening in the septum was reduced from 1.36 +/- 0.20 to 0.98 +/- 0.04 (p less than 0.01) after the induction of LBBB, and the intramyocardial pressure in the septum in diastolic phase, in which the major flow of left anterior descending coronary artery (LAD) exists, increased from 26.6 +/- 10.5 to 57.8 +/- 22.2 mm Hg (p less than 0.02). Mean aortic pressure, LAD flow, and lactate extraction rate showed no significant change. LBBB itself may reduce myocardial perfusion and glucose uptake in the septum because of impaired systolic thickening and augmented intramyocardial pressure in the septum; however, this is not necessarily related to septal ischemia.

18F-fluoro-2′-deoxyuridine as a tracer of nucleic acid metabolism in brain tumors

The value of 18F-fluoro-2'-deoxyuridine (18F-FUdR) as a tracer for nucleic acid metabolism was studied using an experimental rat brain-tumor model. The 18F activity in the tumor tissue 45 minutes after intravenous injection of 18F-FUdR was about 12 times higher than that in the contralateral cortex. Double-labeled autoradiography with 18F-FUdR and 14C-thymidine revealed similar brain-tumor images. In contrast, an autoradiographic comparison of 18F-FUdR with 14C-aminoisobutyric acid, which reveals the impairment of the blood-brain barrier, showed very different images. Also, the 18F radioactivity in the tumor tissue was at a constant level for 30 to 120 minutes, whereas a notable increase in 18F activity with time was observed in nucleotides and acid-insoluble fractions. These results suggest that the distribution pattern of 18F-FUdR closely correlates with the metabolism of nucleic acid and that this drug could be a useful tracer for positron emission tomography.