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Positron emission tomography (PET) radioligands (radioactively labelled tracer compounds) are extremely useful for in vivo characterization of central nervous system drug candidates, neurodegenerative diseases and numerous oncology targets.sup.1. Both tritium and carbon-11 radioisotopologues are generally necessary for in vitro and in vivo characterization of radioligands.sup.2, yet there exist few radiolabelling protocols for the synthesis of either, inhibiting the development of PET radioligands. The synthesis of such radioligands also needs to be very rapid owing to the short half-life of carbon-11. Here we report a versatile and rapid metallaphotoredox-catalysed method for late-stage installation of both tritium and carbon-11 into the desired compounds via methylation of pharmaceutical precursors bearing aryl and alkyl bromides. Methyl groups are among the most prevalent structural elements found in bioactive molecules, and so this synthetic approach simplifies the discovery of radioligands. To demonstrate the breadth of applicability of this technique, we perform rapid synthesis of 20 tritiated and 10 carbon-11-labelled complex pharmaceuticals and PET radioligands, including a one-step radiosynthesis of the clinically used compounds [.sup.11C]UCB-J and [.sup.11C]PHNO. We further outline the direct utility of this protocol for preclinical PET imaging and its translation to automated radiosynthesis for routine radiotracer production in human clinical imaging. We also demonstrate this protocol for the installation of other diverse and pharmaceutically useful isotopes, including carbon-14, carbon-13 and deuterium. A versatile and rapid metallaphotoredox catalytic method of making .sup.3H- and .sup.11C-labelled tracer compounds for use in positron emission tomography (PET) is reported., Author(s): Robert W. Pipal [sup.1] , Kenneth T. Stout [sup.1] , Patricia Z. Musacchio [sup.1] , Sumei Ren [sup.2] , Thomas J. A. Graham [sup.3] , Stefan Verhoog [sup.4] , [...]

Byline: Shreyashi. Jha, Chandana. Nagaraj, R. Mundlamuri, Suvarna. Alladi, Saraswati. Nashi, Raghavendra. Kenchaiah, Anita. Mahadevan, Maya. Bhat, Jitender. Saini, M. Netravathi Background: Fluorodeoxyglucose-positron emission tomography (FDG-PET) in autoimmune encephalitis (AE) [...]

BACKGROUND. Several molecular imaging strategies can identify bacterial infections in humans. PET affords the potential for sensitive infection detection deep within the body. Among PET-based approaches, antibiotic-based radiotracers, which often target key bacterial-specific enzymes, have considerable promise. One question for antibiotic radiotracers is whether antimicrobial resistance (AMR) reduces specific accumulation within bacteria, diminishing the predictive value of the diagnostic test. METHODS. Using a PET radiotracer based on the antibiotic trimethoprim (TMP), [[[sup.11]C]]-TMP, we performed in vitro uptake studies in susceptible and drug-resistant bacterial strains and whole-genome sequencing (WGS) in selected strains to identify TMP resistance mechanisms. Next, we queried the NCBI database of annotated bacterial genomes for WT and resistant dihydrofolate reductase (DHFR) genes. Finally, we initiated a first-in-human protocol of [[sup.11]C]-TMP in patients infected with both TMP-sensitive and TMP-resistant organisms to demonstrate the clinical feasibility of the tool. RESULTS. We observed robust [[sup.11]C]-TMP uptake in our panel of TMP-sensitive and -resistant bacteria, noting relatively variable and decreased uptake in a few strains of P. aeruginosa and E. coli. WGS showed that the vast majority of clinically relevant bacteria harbor a WT copy of DHFR, targetable by [[sup.11]C]-TMP, and that despite the AMR, these strains should be 'imageable.' Clinical imaging of patients with [[sup.11]C]-TMP demonstrated focal radiotracer uptake in areas of infectious lesions. CONCLUSION. This work highlights an approach to imaging bacterial infection in patients, which could affect our understanding of bacterial pathogenesis as well as our ability to better diagnose infections and monitor response to therapy. TRIAL REGISTRATION. ClinicalTrials.gov NCT03424525. FUNDING. Institute for Translational Medicine and Therapeutics, Burroughs Wellcome Fund, NIH Office of the Director Early Independence Award (DP5-OD26386), and University of Pennsylvania NIH T32 Radiology Research Training Grant (5T32EB004311-12)., Introduction The ability to specifically detect and characterize a bacterial infection in a patient has been a long-sought goal for molecular imaging (1). The implications of such a technique are [...]

A new positron emission tomography radiotracer enables imaging of the human glutamate receptor AMPA-R, a fundamental component of neurotransmission involved in neuropsychiatric disorders., Author(s): John H. Krystal [sup.1] Author Affiliations: (1) Department of Psychiatry, Department of Neuroscience, and Department of Psychology, Yale University, New Haven, USA Radiotracers are essential to the non-invasive study [...]

Noninvasive analysis of renal function in conscious mice is necessary to optimize the use of mouse models. In this study, we evaluated whether single photon emission-computed tomography (SPECT) using specific radionuclear tracers can be used to analyze changes in renal proximal tubule functions. The tracers included 99mTC-dimercaptosuccinic acid (99mTc-DMSA), which is used for cortex imaging; 99mTc_mercaptoacetyltriglycine ([sup.99m]Tc-MAG3), used for dynamic renography; and [sup.123]I-[[beta].sub.2]-microglobulin, which monitors receptor-mediated endocytosis. 99mTc-DMSA SPECT imaging was shown to delineate the functional renal cortex with a ~1-mm spatial resolution and accumulated in the cortex reaching a plateau 5 h after injection. The cortical uptake of 99mTc-DMSA was abolished in Clcn5 knockout mice, a model of proximal tubule dysfunction. Dynamic renography with [sup.99m]Tc-MAG3 in conscious mice demonstrated rapid extraction from blood, renal accumulation, and subsequent tubular secretion. Anesthesia induced a significant delay in the 99mTc-MAG3 clearance. The tubular reabsorption of [sup.123]I-[[beta].sub.2]-microglobulin was strongly impaired in the Clcn5 knockout mice, with defective tubular processing and loss of the native tracer in urine, reflecting proximal tubule dysfunction. Longitudinal studies in a model of cisplatin-induced acute tubular injury revealed a correlation between tubular recovery and [sup.123]I-[[beta].sub.2]-microglobulin uptake. These data show that SPECT imaging with well-validated radiotracers allows in vivo investigations of specific proximal tubule functions in conscious mice. receptor-mediated endocytosis; tubular secretion; CIC-5; Dent's disease; radionuclear tracers doi: 10.1152/ajprenal.00413.2009

Estimating the residence times in tumor and normal organs is an essential part of treatment planning for radioimmunotherapy (RIT). This estimation is usually done using a conjugate view whole body scan time series and planar processing. This method has logistical and cost advantages compared to 3-D imaging methods such as Single photon emission computed tomography (SPECT), but, because it does not provide information about the 3-D distribution of activity, it is difficult to fully compensate for effects such as attenuation and background and overlapping activity. Incomplete compensation for these effects reduces the accuracy of the residence time estimates. In this work we compare residence times estimates obtained using planar methods to those from methods based on quantitative SPECT (QSPECT) reconstructions. We have previously developed QSPECT methods that provide compensation for attenuation, scatter, collimator-detector response, and partial volume effects. In this study we compared the use of residence time estimation methods using QSPECT to planar methods. The evaluation was done using the realistic NCAT phantom with organ time activities that model [sup.111]In ibritumomab tiuxetan. Projection data were obtained using Monte Carlo simulations (MCS) that realistically model the image formation process including penetration and scatter in the collimator-detector system. These projection data were used to evaluate the accuracy of residence time estimation using a time series of QSPECT studies, a single QSPECT study combined with planar scans and the planar scans alone. The errors in the residence time estimates were

The purpose of this work was to evaluate myocardial wall motion estimation methods for gated cardiac emission tomography using a dynamic, physical phantom. Wall motion has been increasingly used in 4D image reconstruction methods for improved image quality. A commercially available dynamic phantom was modified by attaching radioactive markers to the phantom myocardial wall. The markers were used to provide an independent measurement of the wall motion throughout the cardiac cycle during a gated SPECT acquisition. Then, without moving the phantom, and after the markers were allowed to decay to negligible levels, the myocardium was injected with [sup.99m]Tc and a gated SPECT scan was acquired. Two wall motion estimation methods were applied to the gated SPECT data. The first method was a standard optical flow algorithm applied to OSEM reconstructions of the myocardial emission data. The second was a simultaneous image reconstruction/motion estimation algorithm. The error in the estimated motion fields was described by the average vector difference between the motion of the markers and the estimated myocardial motion. The simultaneous method gave more accurate motion estimates compared with the optical flow method, and this was more pronounced for larger motion magnitudes. The absolute differences were not great, and the practical implications of these findings are not certain. The physical phantom proved to be an effective tool for evaluating motion estimation methods. Index Terms--Cardiac imaging, gated cardiac emission tomography, image reconstruction, positron emission tomography, single photon emission tomography, wall motion estimation.

MADPET-II is a small animal PET tomograph that features individual Lutetium Oxyorthosilicate (LSO) crystal readout from Avalanche PhotoDiodes (APDs). The detector signals are preamplified by 16-channel fully integrated ASICs which are placed as close as possible to the detector in order to avoid attenuation of the signal or unwanted stray capacitance. However, the power consumption of the preamplifier (30 mW per channel) can cause heat transfer and, consequently, gain drift to temperature sensitive detectors. Temperature measurements on the front-end electronics of MADPET-II have shown a maximum increase of approximately 30[degrees]C in the area around the preamplifier and 10[degrees]C in the area around the APD-LSO detector with respect to room temperature. In the presence of this temperature gradient, energy spectra have been acquired from which a significant drift of the photopeak (3.4% per [degrees]C) and a small increase of the mean energy resolution (3% over the whole temperature range studied) with increasing temperature has been observed. The effect of temperature on the time resolution is small in comparison to the effect of walk and jitter introduced by the analog processing electronics. The behavior of two 4 x 8 LSO-APD front-end detector arrays in coincidence at temperatures below ambient and at various values of the APD bias voltage in terms of energy and time resolution has also been studied. The total current drawn by the APDs (leakage current and photocurrent) has been monitored at various temperatures T and APD bias and was modelled and fitted by a theoretical function demonstrating a T and [e.sup.-1/T] dependence. No significant improvement on time resolution with decreasing temperature has been observed. For temperature stabilization and monitoring, thermoelectric cooling is considered appropriate for mounting in the limited free space of a PET scanner, especially when this is inside an MR scanner for simultaneous PET/MR imaging.

Free-ion selective radiotracer extraction (FISRE) using no-carrier-added [sup.90]Y has been applied to assess the dissociation kinetics of yttrium(III)--1,4,7,10-tetraazacyclododecane-1,4, 7,10-tetraacetic acid (Y--DOTA), a radiopharmaceutical precursor with a remarkable kinetic stability. In order to extend the operationally defined detection window, a complemental FISRE-based experiment has been successfully developed. Within a time frame of approximately 10 half-times of [sup.90]y ([t.sub.1/2] = 61.4 h), the complex Y--DOTA has been observed to form two kinetically distinguishable species with significantly different kinetic properties. The time-dependent speciation was measured to be sensitive to pH variations even in the neutral pH range (4.5-7.4) whereas the impact of ionic strength changes is negligible.

Boric acid enriched in [.sup.10.B] was employed as an artificial ground water tracer at the Rio Hondo Spreading Grounds (RHSG) in Whittier, California. The assumptions regarding conservative tracer transport were supported, as the tracer breakthrough was relatively sharp.

Byline: Yutaka W. Watanabe (1), Akifumi Shimamoto (2), Tsuneo Ono (3) Keywords: Sulfur hexafluoride; trichloro-trifluoroethane; tracer dating techniques; western North Pacific Abstract: To verify the actual usefulness of time-dependent tracer dating techniques in the ocean, we simultaneously obtained two cross sections of sulfur hexafluoride (SF.sub.6) and chlrofluoromethanes (CFC-11, trichlorofluoromethane CFC-12, dichloro-difluromethane CFC-113, trichlorotrifluoroethane) in the western North Pacific in 1998. The vertical distribution patterns of SF.sub.6 and CFC-113 were similar in shape to those of CFC-11 and CFC-12. Maximum penetration depths of SF.sub.6 and CFC-113 remained around 800 m in the subpolar region and 400 m in the tropical region, while the maximum penetration depths of CFC-11 and CFC-12 were still found below 1000 m depth. We also found all maximum contents of these tracers around 26.6-26.8[sigma].sub.I, with a gradual decrease southward. This suggested that a new subsurface water mass in the subpolar region spread out over the entire North Pacific, which agrees closely with previous studies based on the salinity minimum. Moreover, we compared the tracer ages (the elapsed period of a water mass from when the water mass left from the ocean surface) using ten time-dependent tracer dating techniques, CFC-11, CFC-12, CFC-113, SF.sub.6, CFC-11/CFC-12, CFC-113/CFC-11, CFC-113/CFC-12, SF.sub.6/CFC-11, SF.sub.6/CFC-12 and SF.sub.6/CFC-113. This quantitative evaluation of multiple tracer dating techniques in the ocean was the first confirmation of its usefulness based on the observational data on the ocean basin-wide scale. We conclude that SF.sub.6/CFC-11, SF.sub.6/CFC-12, SF.sub.6/CFC-113 and SF.sub.6 dating techniques would be the most promising tools for determining the age of water mass not only just for the past several decades but for the future, too. Author Affiliation: (1) Graduate School of Earth Environmental Science, Hokkaido University, Sapporo, 060-0810, Japan (2) KANSO Co. Ltd., Osaka, 541-0052, Japan (3) Hokkaido National Fisheries Research Institute, Kushiro, 085-0802, Japan Article History: Registration Date: 06/10/2004

Radioactive Marker Technique (RMT), an in-situ method to measure reservoir rock compaction and to evaluate uniaxial compressibility coefficients ([C.sub.m]), is examined here. Recent field applications seems to confirm that RMT-derived [C.sub.m]'s match with sufficient precision with those calculated from land subsidence observed over the field by means of geodetic surveys, but are not always in good agreement with those derived from lab measurements. In particular, here is reported an application of RMT in the Italian Adriatic offshore, which highlights the discrepancies of [C.sub.m]'s measurements from lab and RMT. At present, these discrepancies aren't thoroughly understood, so, from an applicative standpoint, it is still necessary to perform a critical comparison and integration between both set of data. [DOI: 10.1115/1.1506700] Keywords: Formation Compaction, Subsidence, Logging, Radioactive Markers

We have developed a new method to determine the fractional synthesis rate (FSR) and breakdown rate (FBR) of muscle protein. This method involves a pulse tracer injection and measurement of enrichment in the arterial blood and muscle at three time points. The calculations of FSR and FBR are based on the precursor-product principle. To test this method, we gave a pulse injection of L-[ring-[sup.13][C.sub.6]]phenylalanine of 4-6 mg/kg in five rabbits. The measured FBR value (0.233 [+ or -] 0.060%/h) was almost identical (P = 0.35) to that (0.217 [+ or -] 0.078%/h) estimated from a leg arteriovenous balance model (Biolo G, Chinkes D, Zhang X-J, and Wolfe RR. J Parenter Enteral Nutr 16: 305-315, 1992). The measured FSR value tended to be lower than that estimated from the leg model (0.125 [+ or -] 0.036 vs. 0.185 [+ or -] 0.086%/h; P = 0.14), possibly because the new method measures only muscle FSR, whereas the leg balance model also includes skin and bone contributions. The pulse tracer injection did not affect muscle protein kinetics as measured by leucine and phenylalanine kinetics in the leg. In another five rabbits, we demonstrated that sampling could be reduced to either one or two muscle biopsies when multiple pulse injections were used. This method can be completed in 1 h with one muscle biopsy and has technical advantages over currently used methods. stable isotopes; gas chromatograph-mass spectrometer; arteriovenous balance; rabbits