Chemical stability of (99m)Tc-DTPA under aerobic and microbially mediated Fe(III)-reducing conditions in porous media.

(99m)Tc-DTPA has been used as a conservative tracer to quantify water transport through porous media. However, more information on the reactivity of this (99m)Tc compound under varying geochemical conditions is desirable to better understand its potential uses. We measured the speciation of Tc following amendment of (99m)Tc-DTPA to batch systems spanning a range of controlled biogeochemical conditions. Our results suggest that (99m)Tc-DTPA is stable under the reducing conditions tested. However, freshly precipitated Al-ferrihydrite may displace Tc(IV) from DTPA in the absence of Fe(III)-reducing conditions.

Capturing [¹¹C]CO2 for use in aqueous applications.

We present a simple method for trapping [(11)C]CO2 gas and releasing it into a buffered solution using an ion-exchange cartridge. Sodium hydroxide cartridges captured >99% of [(11)C]CO2 following NaOH activation. A sodium bicarbonate solution eluted >99% of trapped radioactivity. Trapping [(11)C]CO2 directly in small volumes of several solutions was less effective than cartridge methods. The recommended methods allow for fast and simple production of highly concentrated carbon-11 containing aqueous solutions for use in filling phantoms, calibrating detectors, or (bio)geochemical experiments.

Monitoring Tc dynamics in a bioreduced sediment: an investigation with gamma camera imaging of (99m)Tc-pertechnetate and (99m)Tc-DTPA.

We demonstrate the utility of nuclear medical imaging technologies and a readily available radiotracer, [(99m)Tc]TcO(4)(-), for the noninvasive monitoring of Fe(II) production in acetate-stimulated sediments from Old Rifle, CO, USA. Microcosms consisting of sediment in artificial groundwater media amended with acetate were probed by repeated injection of radiotracer over three weeks. Gamma camera imaging was used to noninvasively quantify the rate and extent of [(99m)Tc]TcO(4)(-) partitioning from solution to sediment. Aqueous Fe(II) and sediment-associated Fe(II) were also measured and correlated with the observed tracer behavior. For each injection of tracer, curves of (99m)Tc concentration in solution vs time were fitted to an analytic function that accounts for both the observed rate of sedimentation as well as the rate of (99m)Tc association with the sediment. The rate and extent of (99m)Tc association with the biostimulated sediment correlated well with the production of Fe(II), and a mechanism of [(99m)Tc]TcO(4)(-) reduction via reaction with surface-bound Fe(II) to form an immobile Tc(IV) species was inferred. After three weeks of bioreduction, a subset of microcosms was aerated in order to reoxidize the Fe(II) to Fe(III), which also destroyed the affinity of the [(99m)Tc]TcO(4)(-) for the sediments. However, within 3 days postoxidation, the rate of Tc(VII) reduction was faster than immediately before oxidation implying a rapid return to more extensive bioreduction. Furthermore, aeration soon after a tracer injection showed that sediment-bound Tc(IV) is rapidly resolubilized to Tc(VII). In contrast to the [(99m)Tc]TcO(4)(-), a second commercially available tracer, (99m)Tc-DTPA (diethylenetriaminepentaacetic acid), had minimal association with sediment in both controls and biostimulated sediments. These experiments show the promise of [(99m)Tc]TcO(4)(-) and (99m)Tc-DTPA as noninvasive imaging probes for a redox-sensitive radiotracer and a conservative flow tracer, respectively.

Imaging and modeling of flow in porous media using clinical nuclear emission tomography systems and computational fluid dynamics.

This paper presents experimental and modeling aspects of applying nuclear emission tomography to study fluid flow in laboratory packed porous media columns of the type frequently used in geophysics, geochemistry and hydrology research. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are used as non-invasive tools to obtain dynamic 3D images of radioactive tracer concentrations. Dynamic sequences obtained using 18F-FDG PET are used to trace flow through a 5 cm diameter × 20 cm tall sand packed column with and without an impermeable obstacle. In addition, a custom-made rotating column setup placed in a clinical two-headed SPECT camera is used to image 99mTc-DTPA tracer propagation in a through-flowing column (10 cm diameter × 30 cm tall) packed with recovered aquifer sediments. A computational fluid dynamics software package FLUENT is used to model the observed flow dynamics. Tracer distributions obtained in the simulations in the smaller column uniformly packed with sand and in the column with an obstacle are remarkably similar to the reconstructed images in the PET experiments. SPECT results demonstrate strongly non-uniform flow patterns for the larger column slurry-packed with sub-surface sediment and slow upward flow. In the numerical simulation of the SPECT study, two symmetric channels with increased permeability are prescribed along the column walls, which result in the emergence of two well-defined preferential flow paths. Methods and results of this work provide new opportunities in hydrologic and biogeochemical research. The primary target application for developed technologies is non-destructive, non-perturbing, quantitative imaging of flow dynamics within laboratory scale porous media systems.

Dynamic PET denoising with HYPR processing.

HighlY constrained backPRojection (HYPR) is a promising image-processing strategy with widespread application in time-resolved MRI that is also well suited for PET applications requiring time series data. The HYPR technique involves the creation of a composite image from the entire time series. The individual time frames then provide the basis for weighting matrices of the composite. The signal-to-noise ratio (SNR) of the individual time frames can be dramatically improved using the high SNR of the composite image. In this study, we introduced the modified HYPR algorithm (the HYPR method constraining the backprojections to local regions of interest [HYPR-LR]) for the processing of dynamic PET studies. We demonstrated the performance of HYPR-LR in phantom, small-animal, and human studies using qualitative, semiquantitative, and quantitative comparisons. The results demonstrate that significant improvements in SNR can be realized in the PET time series, particularly for voxel-based analysis, without sacrificing spatial resolution. HYPR-LR processing holds great potential in nuclear medicine imaging for all applications with low SNR in dynamic scans, including for the generation of voxel-based parametric images and visualization of rapid radiotracer uptake and distribution.

High-affinity dopamine D2/D3 PET radioligands 18F-fallypride and 11C-FLB457: a comparison of kinetics in extrastriatal regions using a multiple-injection protocol.

(18)F-Fallypride and (11)C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D(2)/D(3) receptors, but differences in their in vivo kinetics may affect the sensitivity for measuring subtle changes in receptor binding. Focusing on regions of low binding, a direct comparison of the kinetics of (18)F-fallypride and (11)C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K(1), k(2), f(ND)k(on), B(max), and k(off) in the midbrain and cortical regions of the rhesus monkey. (11)C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume (K(1)/k(2)) that is three times higher than (18)F-fallypride, primarily due to a slower k(2) (FAL:FLB; k(2)=0.54 min(-1):0.18 min(-1)). The dissociation rate constant, k(off), was slower for (11)C-FLB457, resulting in a lower K(Dapp) than (18)F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D(2)/D(3) binding could be detected in the cerebellum for (11)C-FLB457 but not (18)F-fallypride. Both radioligands can be used to image extrastriatal D(2)/D(3) receptors, with (11)C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and (18)F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D(2)/D(3) binding in the cerebellum, reference region analysis methods will give a greater bias in BP(ND) with (11)C-FLB457 than with (18)F-fallypride.

PET measurement of changes in D2/D3 dopamine receptor binding in a nonhuman primate during chronic deep brain stimulation of the bed nucleus of the stria terminalis.

UNLABELLED: PET imaging is a powerful tool for measuring physiological changes in the brain during deep brain stimulation (DBS). In this work, we acquired five PET scans using a highly selective D2/D3 dopamine antagonist, 18F-fallypride, to track changes in dopamine receptor availability, as measured by the distribution volume ratio (DVR), through the course of DBS in the bed nucleus of the stria terminalis (BNST) in a nonhuman primate. METHODS: PET scans were performed on a rhesus monkey with unilateral BNST stimulation during periods of baseline, chronic high frequency (130 Hz) and low frequency (50 Hz) DBS stimulation, and during a washout period between stimulation periods. A final scan was performed with the electrode stimulation starting 110 min into the scan. Whole brain parametric images of (18)F-fallypride DVR were calculated for each condition to track changes in both striatal and extrastriatal D2/D3 availability. RESULTS: The monkey displayed significant increases in receptor binding throughout the brain during DBS relative to baseline for 130 and 50 Hz, with changes in DVR of: caudate 42%, 51%; putamen 56%, 57%; thalamus 33%, 49%; substantia nigra 29%, 26%; and prefrontal cortex 28%, 56%, respectively. Washout and post-stimulation scans revealed DVR values close to baseline values. Activating the stimulator midway through the final scan resulted in no statistically significant changes in binding. CONCLUSIONS: PET neuroligand imaging has demonstrated the sensitivity to track changes in dopamine D2/D3 binding during the course of DBS. These methods show great potential for providing insight into the neurochemical consequences of DBS.

The distribution of D2/D3 receptor binding in the adolescent rhesus monkey using small animal PET imaging.

UNLABELLED: PET imaging of the neuroreceptor systems in the brain has earned a prominent role in studying normal development, neuropsychiatric illness and developing targeted drugs. The dopaminergic system is of particular interest due to its role in the development of cognitive function and mood as well as its suspected involvement in neuropsychiatric illness. Nonhuman primate animal models provide a valuable resource for relating neurochemical changes to behavior. To facilitate comparison within and between primate models, we report in vivo D2/D3 binding in a large cohort of adolescent rhesus monkeys. METHODS: In this work, the in vivo D2/D3 dopamine receptor availability was measured in a cohort of 33 rhesus monkeys in the adolescent stage of development (3.2-5.3 years). Both striatal and extrastriatal D2/D3 binding were measured using [F-18]fallypride with a high resolution small animal PET scanner. The distribution volume ratio (DVR) was measured for all subjects and group comparisons of D2/D3 binding among the cohort were made based on age and sex. Because two sequential studies were acquired from a single [F-18]fallypride batch, the effect of competing (unlabeled) ligand mass was also investigated. RESULTS: Among this cohort, the rank order of regional D2/D3 receptor binding did not vary from previous studies with adult rhesus monkeys, with: putamen>caudate>ventral striatum>amygdala approximately substantia nigra>medial dorsal thalamus>lateral temporal cortex approximately frontal cortex. The DVR coefficient of variation ranged from 14%-26%, with the greatest variance seen in the head of the caudate. There were significant sex differences in [F-18]fallypride kinetics in the pituitary gland, but this was not observed for regions within the blood-brain barrier. Furthermore, no regions in the brain showed significant sex or age related differences in DVR within this small age range. Based on a wide range of injected fallypride mass across the cohort, significant competition effects could only be detected in the substantia nigra, thalamus, and frontal cortex, and were not evident above intersubject variability in all other regions. CONCLUSION: These data represent the first report of large cohort in vivo D2/D3 dopamine whole brain binding in the adolescent brain and will serve as a valuable comparison for understanding dopamine changes during this critical time of development and provide a framework for creating a dopaminergic biochemical atlas for the rhesus monkey.