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Biomedical subjects

G K Mulholland

Publications and source records attributed to G K Mulholland.

At least 19 recordsLinked to original sources
PubMed1999

PET imaging of the pre-synaptic dopamine uptake sites in rapid-onset dystonia-parkinsonism (RDP).

BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a genetic movement disorder characterized by abrupt onset over hours to days of bradykinesia, postural instability, dysphagia, dysarthria, and severe dystonic spasms with decreased levels of the dopamine metabolite, homovanillic acid (HVA), in cerebrospinal fluid (CSF). METHODS: We imaged the dopamine re-uptake system with [O-methyl-11C]beta-CFT ([11C]beta-CFT) in three severely affected individuals with RDP and four patients with idiopathic Parkinson's disease (IPD). Results were compared with those of age-matched normal volunteers. RESULTS: Positron emission tomography images from those patients with IPD demonstrated a dramatic reduction in the volume of distribution of [11C]beta-CFT whereas patients with RDP showed slightly elevated values. CONCLUSIONS: The data suggest that patients with RDP do not have a decrease in the number of dopamine re-uptake sites. Our findings suggest that, unlike the situation in IPD, low CSF HVA concentrations seen in RDP patients are not the result of degeneration of striatal dopamine terminals or loss of dopamine re-uptake sites.

Adult↗
PubMed1998

Heterogeneous atrial denervation creates substrate for sustained atrial fibrillation.

BACKGROUND: Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. METHODS AND RESULTS: After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation. Dogs then underwent PET imaging with either a sympathetic ([11C]hydroxyephedrine, HED) or parasympathetic (5-[11C]methoxybenzovesamicol, MOBV) nerve label. None of the animals had sustained AF (>60 minutes) at baseline. None of the sham dogs and 14 of 15 phenol dogs had sustained AF at follow-up. Sites to which phenol was applied had a significantly shorter ERP (136+/-17.6 ms) than those same sites in the sham controls (156+/-19.1 ms) (P=0.01). Although there was no difference in the ERP change with either vagal or sympathetic stimulation alone between phenol and nonphenol sites, the percent decrease in ERP with simultaneous vagal/sympathetic stimulation was greater in the phenol sites (17+/-8%) than in the nonphenol sites (9+/-9%) (P=0.01). There was a significantly increased dispersion of refractoriness (21+/-6.4 ms in the sham versus 58+/-14 ms in the phenol dogs, P=0.01) as well as dispersion of AF cycle length (49+/-10 ms in the sham versus 105+/-12 ms in the phenol dogs, P=0.0001). PET images demonstrated defects of HED uptake in the areas of phenol application, with no defect of MOBV uptake. CONCLUSIONS: Heterogeneous sympathetic atrial denervation with phenol facilitates sustained AF.

Animals↗
PubMed1998

[18F]fluoroethoxy-benzovesamicol, a PET radiotracer for the vesicular acetylcholine transporter and cholinergic synapses.

Loss of cholinergic transmission in the cortex and hippocampus is a characteristic feature of Alzheimer's disease, and visualization of functional cholinergic synapses in the brain with PET could be a useful method for studying this degenerative condition in living humans. We investigated [18F]fluoroethoxybenzovesamicol, (-)-[18F] FEOBV,(-)-(2R,3R)-trans-2-hydroxy-3-(4-phenylpiperidino)-5-(2-[18F ]fluoroethoxy)-1,2,3,4-tetralin, a high affinity positron emitting ligand for the vesicular acetylcholine transporter, as a potential in vivo cholinergic synapse mapping agent. Rodent biodistribution, dosimetry, stereospecificity of biological effects, pharmacologic blocking studies, in vivo rodent brain autoradiography and metabolites were examined. (-)-[18F]FEOBV brain uptake following intravenous injection was robust, with 2.65% dose/brain in mice at 5 min, and the regional localization matched the known distributions of presynaptic cholinergic markers at later times. Both the cholinergic localization and curare-like effects of FEOBV were associated with the "(-)"-enantiomer exclusively. (-)-[18F]FEOBV regional brain distribution in rodents was changed little by pretreatment with haloperidol, (+)-3-PPP, or E-2020, indicating FEOBV, unlike other vesamicol analogs, did not interact in vivo with dopamine or sigma receptor systems. Autoradiography of rat brain 3 h following i.v. injection of (-)-[18F]FEOBV showed high localization in brain areas rich in presynaptic cholinergic elements. Metabolic defluorination in rodents was modest, and analysis of brain tissue following tracer administration found FEOBV as the only extractable radioactive species. (-)-[18F]FEOBV dosimetry calculated from rat data estimate 10 mCi doses can be given to humans. These studies show FEOBV maps cholinergic areas with high specificity in vivo, and may provide a noninvasive means to safely and accurately gauge the functional integrity of cholinergic synapses in man using PET.

Acetylcholine↗
PubMed1998

Quantification of muscarinic cholinergic receptors with [11C]NMPB and positron emission tomography: method development and differentiation of tracer delivery from receptor binding.

Quantification of human brain muscarinic cholinergic receptors was investigated with the use of [11C]N-methyl-4-piperidyl benzylate (NMPB) and positron emission tomography (PET). Whole-brain uptake of NMPB at 90 to 110 minutes after intravenous injection was approximately 10% of the administered dose. The initial cerebral distribution of NMPB corresponded to the pattern of cerebral perfusion; however, at progressively longer postinjection intervals, regional distinctions consistent with muscarinic receptor binding were evident: activity at 90 to 110 minutes postinjection was highest in the striatum and cerebral cortex, intermediate in the thalamus and pons, and lowest in the cerebellum. After the development of a chromatographic system for isolation of authentic [11C]NMPB in plasma, tracer kinetic modeling was used to estimate receptor binding from the cerebral and arterial plasma tracer time-courses. Ligand transport rate and receptor-binding estimates were obtained with the use of compartmental models and analytical methods of varying complexity, including a two-parameter pixel-by-pixel-weighted integral approach and regional least-squares curve-fitting analyses employing both two- and three-compartment model configurations. In test-retest experiments, precision of the methods and their abilities to distinguish altered ligand delivery from binding in occipital cortex during an audiovisual presentation were evaluated. Visual stimulation increased the occipital blood-to-brain NMPB transport rate by 25% to 46% in estimates arising from the various approaches. Weighted integral analyses resulted in lowest apparent transport changes and in a concomitant trend toward apparent binding increases during visual activation. The regional least-squares procedures were superior to the pixel-by-pixel method in isolating the effects of altered tracer delivery from receptor-binding estimates, indicating larger transport effects and unaltered binding. Precision was best (less than 10% test-retest differences) for the weighted integral analyses and was somewhat lower in the least-squares analyses (10-25% differences). The authors conclude that pixel-by-pixel-weighted integral analyses of NMPB distribution introduce transport biases into receptor-binding estimates. Similar confounding effects also are predicted in noncompartmental analyses of delayed radiotracer distribution. The use of regional nonlinear least-squares fitting to two- and three-compartment models, although more labor intensive, provides accurate distinction of receptor-binding estimates from tracer delivery with acceptable precision in both intra- and intersubject comparisons.

Adult↗
PubMed1996

Vesamicol receptor mapping of brain cholinergic neurons with radioiodine-labeled positional isomers of benzovesamicol.

UNLABELLED: Alzheimer's disease is characterized by progressive cerebral cholinergic neuronal degeneration. Radiotracer analogs of benzovesamicol, which bind with high affinity to the vesamicol receptor located on the uptake transporter of acetylcholine storage vesicles, may provide an in vivo marker of cholinergic neuronal integrity. Five positional isomers of racemic iodobenzovesamicol (4'-, 5-, 6-, 7-, and 8-IBVM) were synthesized, exchange-labeled with iodine-125, and evaluated as possible in vivo markers for central cholinergic neurons. Only two isomers, 5-IBVM (5) and 6-IBVM (10), gave distribution patterns in mouse brain consistent with cholinergic innervation: striatum >> hippocampus > or = cortex > hypothalamus >> cerebellum. The 24-h tissue-to-cerebellum concentration ratios for 5-IBVM (5) were 3-4-fold higher for striatum, cortex, and hippocampus than the respective ratios for 6-IBVM (10). Neither 8-IBVM (16) nor 4'-IBVM (17) exhibited selective retention in any of the brain regions examined. In the heart, only 5-IBVM (5) exhibited an atria-to-ventricles concentration ratio consistent with high peripheral cholinergic neuronal selectivity. The 7-IBVM (14) isomer exhibited an anomalous brain distribution pattern, marked by high and prolonged retention in the five brain regions, most notably the cerebellum. This isomer was screened for binding in a series of 26 different biological assays; 7-IBVM (14) exhibited affinity only for the delta-receptor with an IC50 of approximately 30 nM. Drug-blocking studies suggested that brain retention of 7-IBVM (14) reflects high-affinity binding to both vesamicol and delta-receptors. Competitive binding studies using rat cortical homogenates gave IC50 values for binding to the vesamicol receptor of 2.5 nM for 5-IBVM (5), 4.8 nM for 6-IBVM (10), and 3.5 nM for 7-IBVM (14). Ex vivo autoradiography of rat brain after injection of (-)-5-[125I]IBVM ((-)-[125I]5) clearly delineated small cholinergic-rich areas such as basolateral amygdala, interpeduncular nucleus, and facial nuclei. Except for cortex, regional brain levels of (-)-5-[123I]IBVM ((-)-[123I]5) at 4 h exhibited a linear correlation (r2 = 0.99) with endogenous levels of choline acetyltransferase. CONCLUSION: Vesamicol receptor mapping of cholinergic nerve terminals in murine brain can be achieved with 5-IBVM (5) and less robustly with 6-IBVM (10), whereas the brain localization of 7-IBVM (14) reflects high-affinity binding to both vesamicol and delta-receptors.

Alzheimer Disease↗
PubMed1996

Back-to-back "one-pot" [18F]FDG syntheses in a single Siemens-CTI chemistry process control unit.

Simple changes in the chemistry, plumbing, and programming of the Siemens-CTI chemistry process control unit (CPCU) effectively double its output by enabling two back-to-back "1-pot" syntheses of 2-[18F]fluoro-2-deoxy-D-glucose in a single unit. Replacement of Kryptofix 2.2.2 with tetramethylammonium carbonate and elimination of diethyl ether from the procedure shorten synthesis time to 48 min, improve process and end-product safety, and increase end-of-synthesis yields from 37% to 52% by minimizing steps and transfer losses.

Animals↗
PubMed1996

Improved synthesis of beta-CIT and [11C]beta-CIT labeled at nitrogen or oxygen positions.

The important radiotracer precursor 2 beta-carbomethoxy-3 beta-(4-idophenyl)-tropane (beta-CIT, RTI-55) was made in 52% overall yield from cocaine. Key steps were improved conjugate Grignard addition to anhydroecgonine methyl ester with > 3.5:1 2 beta: 2 alpha-isomer selectivity, and a mild new direct aromatic iodination with I2 and silver triflate in CH2Cl2. The [11C]beta-CIT was labeled at either the N or O positions with [11C]methyl triflate; and efficient reversed-phase HPLC was used to preparatively separate [N-11C]beta-CIT from N-nor-beta-CIT for the first time, and a fast solid-phase extraction (SPE) method was applied to preparatively separate [O-11C]beta-CIT from beta-CIT-acid precursor.

Carbon Radioisotopes↗
PubMed1996

In vivo quantification of cerebral muscarinic receptors in normal human aging using positron emission tomography and [11C]tropanyl benzilate.

Regional cerebral muscarinic cholinergic receptor binding was quantified in normal young and elderly subjects employing the muscarinic antagonist radioligand [11C]tropanyl benzilate (TRB). Binding was determined by kinetic analyses of positron emission tomographic (PET) determinations of cerebral activity in conjunction with radial arterial blood sampling following intravenous radiotracer injection. A significant, but minor (8%), loss of frontal cortical receptors relative to whole brain average receptor density was found with advancing age. Parametric estimates of binding suggest small reductions in cerebral cortex binding as well as increases in brain stem and cerebellar binding underlying the observed pattern difference. However, these latter changes did not achieve statistical significance. We conclude that cerebral muscarinic receptor availability, as depicted by antagonist binding, does not undergo a major decline during normal aging of the adult human brain. The cerebral cortical cholinergic dysfunction in elderly subjects, suggested by prior clinical evidence, is not attributable to major loss of total muscarinic cholinoceptive capacity.

Adult↗
PubMed1996

Kinetic evaluation of positron-emitting muscarinic receptor ligands employing direct intracarotid injection.

The development and characterization of new receptor ligands for in vivo binding assays are often both lengthy and expensive. It is therefore desirable to predict the suitability of a ligand early in the process of its evaluation. In the present study, compartmental analysis following intracarotid ligand injection in the monkey is used to evaluate the in vivo kinetics of the muscarinic cholinergic receptor antagonists [11C]tropanyl benzilate ([11C]TRB) and [11C]N-methylpiperidyl benzilate ([11C]NMPB). Animals were implanted with chronic subcutaneous access ports and indwelling catheters with tips located in the common carotid artery, just proximal to its bifurcation. The external carotid artery was ligated to ensure selective tracer delivery through the internal carotid artery to the brain. Positron emission tomography was used to measure brain tissue time-activity curves following tracer injections. CBF was estimated from the clearance of [15O]H2O, and receptor ligand distributions were analyzed according to a physiologic model consisting of an intravascular compartment and nonspecific plus free and receptor-bound tissue ligand compartments. In [11C]TRB studies, marked reductions in the forward ligand-receptor binding rate and in both the total and the specific binding tissue-to-plasma volumes of ligand distribution were observed after scopolamine receptor blockade or with low administered specific activity. Conversely, neither the distribution volume of the nonspecific plus free ligand compartment nor the rate of ligand dissociation from receptor sites was affected. In [11C]NMPB studies, tissue compartments describing specific binding and nonsaturable components could not be reliably separated. The receptor-related term in this case, the total tissue-to-plasma distribution volume, demonstrated reduction after low specific activity ligand injection. Comparison of the two ligands suggests that NMPB interacts more rapidly with the receptors and has a lower apparent volume of distribution than does TRB. Thus, NMPB may be the more suitable ligand if accurate estimates of binding dissociation rate are limited by temporal constraints or if simplified, one-tissue-compartment analyses are used. The carotid injection method appears promising for the initial evaluation of ligand kinetics, permitting physiologic compartmental analyses without measurement of input functions or chromatography of blood samples.

Animals↗
PubMed1995

Synthesis, in vivo biodistribution and dosimetry of [11C]N-methylpiperidyl benzilate ([11C]NMPB), a muscarinic acetylcholine receptor antagonist.

4-N-Methylpiperidyl benzilate (NMPB), a high affinity antagonist for the muscarinic cholinergic receptor, has been synthesized in carbon-11-labeled form through the N-[11C]methylation of 4-piperidylbenzilate. The product was isolated by HPLC, and obtained in yields (> 100 mCi) and specific activities (500-3000 Ci/mmol) sufficient for in vivo evaluation in small animals. Time-dependent regional brain distributions in rats and mice showed high radiotracer uptake and retention in striatum and cortex, and low in cerebellum, consistent with muscarinic cholinergic receptor distributions. Radiotracer retention in tissues could be significantly reduced by pretreatment of animals with a large dose of a competing antagonist, quiniclidinyl benzilate. Whole body biodistribution in rats was used to calculate the expected human internal radiation dosimetry for this new radiopharmaceutical. These animal experiments formed the basis for subsequent introduction of [11C]NMPB into human use with positron emission tomography.

Animals↗
PubMed1995

Solid-phase reversible trap for [11C]carbon dioxide using carbon molecular sieves.

A simple, maintenance-free trapping technique which concentrates and purifies no-carrier-added 11CO2 from gas targets is described. The trap requires no liquid nitrogen cooling and has no moving parts besides solenoid valves. It employs carbon molecular sieves to adsorb 11CO2 selectively from gas targets at room temperature. Nitrogen, O2, CO, NO and moisture in the target gas which could interfere with subsequent radiochemical steps are not retained. Trapping efficiency of 1 g of sieve for 11CO2 from a 240 cm3 target gas dump and helium flush cycle is > 99%, and the adsorbed 11CO2 is recovered quantitatively as a small concentrated bolus from the carbon sieve trap by thermal desorption. This durable trap has performed reliably for more than 1 y with a single charge of carbon sieve. It has simplified the production, and improved the yields of several 11C-radiochemicals at this laboratory.

Carbon Dioxide↗
PubMed1995

Simple rapid hydrolysis of acetyl protecting groups in the FDG synthesis using cation exchange resins.

A new solid phase method for hydrolysis of acetyl groups from the intermediate 2-[18F]fluoro-2-deoxyglucose tetraacetate ([18F]FDG-Ac4) was developed. Fast cleavage occurs with Dowex 50 sulfonic acid resin (H+ form) at approximately 100 degrees C in the absence of bulk water. [18F]FDG-Ac4 reaction mixtures were efficiently converted to neutral aqueous solutions of pure FDG in 10-15 min. The method avoids problems associated with liquid acids and can be easily integrated into existing [18F]FDG procedures.

Cation Exchange Resins↗
PubMed1994

Evaluation of (-)[18F]fluoroethoxybenzovesamicol as a new PET tracer of cholinergic neurons of the heart.

18F-labeled (-)fluoroethoxybenzovesamicol [(-)FEOBV] is a novel PET tracer which binds to the vesicular acetylcholine transporter of cholinergic neurons. To evaluate the in vivo binding specificity and kinetic properties of (-)FEOBV, studies were performed in isolated working rat hearts. External gamma,gamma-coincidence monitoring of hearts indicated high extraction of radiotracer by the myocardium and rapid wash-out of unbound tracer (> 90% of maximal accumulation) within 5 min. Inclusion of (-)vesamicol (10 microM) throughout perfusion decreased the retention of (-)FEOBV by 71% (P < 0.005) and 76% (P < 0.005) in atria and ventricles, respectively. However, the initial uptake rate of the tracer was unaffected. Additional experiments showed the inactive stereoisomer, (+)FEOBV, to have a lower retention than the (-)FEOBV isomer in ventricles, indicating stereospecificity of the binding process that is consistent with structure-activity relationships of vesamicol congeners. The results indicate (-)FEOBV to be a moderately specific probe of vesamicol-sensitive binding in cholinergic neurons of the heart in experimental conditions that assure adequate washout of unbound tracer. However, the utility of the radiotracer for in vivo studies with PET is likely to be limited by the low rate of specific binding in myocardium consistent with the low density of cholinergic neurons in the heart.

Acetylcholine↗
PubMed1994

[11C]tropanyl benzilate-binding to muscarinic cholinergic receptors: methodology and kinetic modeling alternatives.

Quantitative estimation of cerebral muscarinic receptors was investigated with the use of the antagonist [11C]tropanyl benzilate ([11C]TRB) and positron emission tomography (PET). Kinetic modeling alternatives were examined with the goal of identifying an analysis method providing stable receptor measures, yet avoiding biases from inappropriate reductions in model complexity. Dynamic PET scans were performed on six young normal volunteers. Several modeling approaches yielding relative receptor density measures were evaluated: (a) a single "late" scan using relative tracer concentration values; (b) a slope estimate from graphic analysis (Patlak plot); (c) a two-compartment, two-parameter model (transport and total ligand distribution volume); (d) a three-compartment, two-parameter model using the free+nonspecific distribution volume, DV', fixed to the cerebellar value; (e) an early scan for transport, a fixed value for DV', and a single late scan for the binding rate constant; and (f) a three-compartment, three-parameter model. Both computer simulations and PET scan results indicate all methods provide receptor density index measures with the same rank order as in vitro measures. Oversimplified approaches (methods 1 and 2) yield a more highly nonlinear relation between the estimated receptor density index and the known receptor density than do methods retaining greater model complexity (methods 3-6). However, noise propagation into the receptor measure is greater for the more complex methods. Reliable receptor density information can be obtained from kinetic [11C]TRB PET studies, with methods 3-5 providing the most appropriate levels of model complexity for estimates of relative muscarinic receptor density.

Adult↗
PubMed1992

In vivo muscarinic cholinergic receptor imaging in human brain with [11C]scopolamine and positron emission tomography.

Cerebral muscarinic cholinergic receptors were imaged and regionally quantified in vivo in humans with the use of [11C]scopolamine and positron emission tomography. Previous studies in experimental animals have suggested the utility of radiolabeled scopolamine for in vivo measurements, on the bases of its maintained pharmacologic specificity following systemic administration and the exclusion of labeled metabolites from the brain. The present studies describe the cerebral distribution kinetics of [11C]scopolamine in normal subjects following intravenous injection. Scopolamine is initially delivered to brain in a perfusion-directed pattern. After 30 to 60 min, activity is lost preferentially from cerebral structures with low muscarinic receptor density including the cerebellum and thalamus. Activity continues to accumulate throughout a 2 h postinjection period in receptor-rich areas including cerebral cortex and the basal ganglia. The late regional concentration of [11C]scopolamine does not, however, accurately parallel known differences in muscarinic receptor numbers in these receptor-rich areas. Tracer kinetic analysis of the data, performed on the basis of a three-compartment model, provides receptor binding estimates in good agreement with prior in vitro measurements. Kinetic analysis confirms significant contributions of ligand delivery and extraction to the late distribution of [11C]scopolamine, reconciling the discrepancy between receptor levels and tracer concentration. Finally, a novel dual-isotope method for rapid chromatographic processing of arterial blood samples in radiotracer studies is presented. The combination of rapid chromatography and compartmental analysis of tracer distribution should have broad utility in future in vivo studies with short-lived radioligands.

Brain↗
PubMed1992

Synthesis, rodent biodistribution, dosimetry, metabolism, and monkey images of carbon-11-labeled (+)-2 alpha-tropanyl benzilate: a central muscarinic receptor imaging agent.

Muscarinic cholinergic receptors (mAChR) are abundant in the brain, and the mAChR system mediates many aspects of brain function. There is evidence of alterations in muscarinic binding in degenerative brain disorders. A muscarinic receptor radioligand, carbon-11-(+)-2 alpha-tropanyl benzilate ([11C]TRB), has been prepared through N-[11C]methylation of N-desmethyl TRB, and evaluated in rodents and primates. Full body biodistribution in rats has been determined and the expected human dosimetry calculated. Comparisons with [11C]scopolamine in rats showed 2-6 times greater brain uptake of [11C] TRB. Highly specific and saturable binding of [11C]TRB in the striatum and cortex was demonstrated by greater than 85% blockade of uptake following QNB or scopolamine pretreatment. Striatum/cerebellum ratios in mice at 60 min exceeded 12.6. TLC analysis of rat tissues showed the absence of 11C-metabolites in brain and heart, and a rapid solid phase C-18 Sep-Pak method found that unmetabolized plasma [11C]TRB in monkeys fell from 81% at 5 min to 48% at 80 min. Finally, brains of living primates have been imaged using PET and [11C]TRB; regional localization was consistent with muscarinic receptor distribution. These results represent intermediate steps in the development of [11C]TRB for quantification of central muscarinic receptors in man.

Animals↗
PubMed1991

Recovery and purification of no-carrier-added [18F]fluoride with bistrimethylsilylsulfate (BTMSS).

No-carrier-added trimethylsilyl[18F]fluoride (TMS[18F]F) was rapidly liberated from a variety of dry supports containing unreactive [18F]fluoride by simply heating with neat bistrimethylsilylsulfate. The supports included calcium phosphate, anion exchange resins, alumina, borosilicate and porous carbon beads, to which [18F]fluoride was applied by absorption or evaporation of aqueous solution. TMS[18F]F was evolved essentially free of entrained moisture or excess silylating agent and was efficiently absorbed and rapidly cleaved to free [18F]fluoride ion by 0.1% benzyltrimethylammonium methoxide in anhydrous methanol. Passage of this solution through a strong cation exchange column provided purified hydrogen[18F]fluoride, which was subsequently trapped on a quaternary 4-aminopyridinium resin and used for heterogeneous nucleophilic radiofluorination of 1,3,4,6-tetraacetyl-beta-mannopyranose-2-triflate in 70% yield. The purified [18F]fluoride was also used for solution phase nucleophilic labeling of ethyl [18F]4-fluorobenzoate following addition of K2 CO3/Kryptofix and DMSO. This approach provides a simplified way to ensure high reactivity in [18F]fluoride ion from cyclotron targets. It also may be used to salvage active [18F]fluoride ion from insoluble complexes and radiofluorination reaction residues.

Chromatography↗