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Three experiments investigated 3-, 4-, and 5-year-olds' (N = 240) understanding that their future or "grown-up" preferences may differ from their current ones (self-future condition). This understanding was compared to children's understanding of the preferences of a grown-up (adult-now condition) or the grown-up preferences of a same-aged peer (peer-future condition). Children's performance across all three conditions improved significantly with age. Moreover, children found it significantly more difficult to reason about their own future preferences than they did to reason either about an adult's preferences or the future preferences of a peer. These results have important implications for theories about future thinking and perspective-taking abilities, more broadly., (© 2014 The Authors. Child Development © 2014 Society for Research in Child Development, Inc.)

Activated macrophages play a significant role in initiation and progression of inflammatory diseases and may serve as the basis for the development of targeted diagnostic methods for imaging sites of inflammation. Folate receptor beta (FR-β) is differentially expressed on activated macrophages associated with inflammatory disease states yet is absent in either quiescent or resting macrophages. Because folate binds with high affinity to FR-β, development of folate directed imaging agents has proceeded rapidly in the past decade. However, reports of PET based imaging agents for use in inflammatory conditions remain limited. To investigate whether FR-β expressing macrophages could be exploited for PET based inflammatory imaging, two separate folate-targeted PET imaging agents were developed, 4-[(18)F]-fluorophenylfolate and [(68)Ga]-DOTA-folate, and their ability to target activated macrophages were examined in a rodent inflammatory paw model. We further compared inflamed tissue uptake with 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]-FDG). microPET analysis demonstrated that both folate-targeted PET tracers had higher uptake in the inflamed paw compared to the control paw. When these radiotracers were compared to [(18)F]-FDG, both folate PET tracers had a higher signal-to-noise ratio (SNR) than [(18)F]-FDG, suggesting that folate tracers may be superior to [(18)F]-FDG in detecting diseases with an inflammatory component. Moreover, both folate-PET imaging agents also bind to FR-α which is overexpressed on multiple human cancers. Therefore, these folate derived PET tracers may also find use for localizing and staging FR(+) cancers, monitoring response to therapy, and for selecting patients for tandem folate-targeted therapies.

Unlabelled: 2-((2S,5R,8S,11S)-5-benzyl-8-(4-((2S,3R,4R,5R,6S)-6-((2-(4-(3-(18)F-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)butyl)-11-(3-guanidinopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentaazacyclopentadecan-2-yl)acetic acid ((18)F-RGD-K5) has been developed as an α(v)β(3) integrin marker for PET. The purpose of this study was to determine the biodistribution and estimate the radiation dose from (18)F-RGD-K5 using whole-body PET/CT scans in monkeys and humans., Methods: Successive whole-body PET/CT scans were obtained after intravenous injection of (18)F-RGD-K5 in 3 rhesus monkeys (167 ± 19 MBq) and 4 healthy humans (583 ± 78 MBq). In humans, blood samples were collected between the PET/CT scans, and stability of (18)F-RGD-K5 was assessed. Urine was also collected between the scans, to determine the total activity excreted in urine. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on human and monkey biodistributions., Results: (18)F-RGD-K5 was metabolically stable in human blood up to 90 min after injection, and it cleared rapidly from the blood pool, with a 12-min half-time. For both monkeys and humans, increased (18)F-RGD-K5 uptake was observed in the kidneys, bladder, liver, and gallbladder, with mean standardized uptake values at 1 h after injection for humans being approximately 20, 50, 4, and 10, respectively. For human biodistribution data, the calculated effective dose was 31 ± 1 μSv/MBq, and the urinary bladder wall had the highest absorbed dose at 376 ± 19 μGy/MBq using the 4.8-h bladder-voiding model. With the 1-h voiding model, these doses reduced to 15 ± 1 μSv/MBq for the effective dose and 103 ± 4 μGy/MBq for the absorbed dose in the urinary bladder wall. For a typical injected activity of 555 MBq, the effective dose would be 17.2 ± 0.6 mSv for the 4.8-h model, reducing to 8.3 ± 0.4 mSv for the 1-h model. For monkey biodistribution data, the effective dose to humans would be 22.2 ± 2.4 mSv for the 4.8-h model and 12.8 ± 0.2 mSv for the 1-h model., Conclusion: The biodistribution profile of (18)F-RGD-K5 in monkeys and humans was similar, with increased uptake in the bladder, liver, and kidneys. There was rapid clearance of (18)F-RGD-K5 through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both whole-body effective dose and bladder dose can be reduced by more frequent voiding. (18)F-RGD-K5 can be used safely for imaging α(v)β(3) integrin expression in humans.

Objectives: F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans., Methods: Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software., Results: The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data., Conclusion: Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

Introduction: The metabotropic glutamate receptor subtype 5 (mGluR5) is distributed throughout the central nervous system (CNS), and has been suggested to be a potential target for several CNS disorders suchas Parkinson's disease, pain, anxiety, depression, schizophrenia, and addiction. We report here on the rhesus monkey biodistribution and radiation dosimetry of [18F]3-fluoro-5-[(pyridine-3-yl)ethynyl]benzonitrile, [18F]F-PEB, a mGluR5 positron emission tomography (PET) radiotracer., Methods: Three male and two female rhesus monkeys were imaged using the Discovery ST PET/computed tomography scanner. A total of 25 whole body PET emissions were acquired over 3 h (23 emissions in one subject). Regions of interest were drawn in the brain, lungs, heart, liver, spleen, bladder, and testes. The absorbed radiation dose was calculated using OLINDA v1., Results: At the end of the imaging session, 45% of the [18F]F-PEB activity had been excreted by the liver and into the gastrointestinal tract and 10% had been excreted into the urinary bladder. When extrapolating to the adult human, the largest absorbed radiation doses were located in the upper large intestine (males: 0.18 mGy/MBq, females: 0.20 mGy/MBq) and small intestine (males: 0.16 mGy/MBq, females: 0.19 mGy/MBq). Effective radiation dose was 0.033 mSv/MBq for males and 0.034 mSv/MBq for females, similar to many other [18F] ligands., Conclusion: The effective radiation dose of [18F]F-PEB obtained from rhesus is similar to many other clinically utilized [18F] ligands.

Background: The amyloid neuritic plaque is considered to be a toxic collection of amyloid-ss protein found in brain tissue in Alzheimer's disease. A neutral analogue of the amyloid-binding thioflavin-T (BTA), has been radiolabeled as [C-11]-6-OH-BTA-1. It crosses the blood brain barrier, and is a promising tracer for imaging plaques in vivo using positron emission tomography. We now report the biodistribution and dosimetry of [C-11]-6-OH-BTA-1 in baboons., Methods: Four 2-hour whole body studies were acquired in an ECAT ACCEL camera in two baboons after the bolus injection of [C-11]-6-OH-BTA-1. After 3.5 minute transmission scans performed per bed position prior to injection, emission scans were collected in 2-D mode over five bed positions. Regions of interest (ROI) were drawn around the brain, left and right lungs, heart, liver, gall bladder, left and right kidneys, spleen and urinary bladder. Since no fluid was removed from the baboons, total body radioactivity was calculated using the injected dose and a calibration factor determined from a cylinder phantom. The area under the curve (AUC) for each ROI was determined by trapezoidal integration of the first few points with subsequent points fit by a decreasing monoexponential. The AUC was then divided by counts in the total body, and resulting residence times were entered into the MIRDOSE3 program., Results: The animals tolerated the procedure well. The ligand was eliminated via the hepatobiliary and renal systems. In the adult male and female reference the gallbladder received the highest estimated radiation dose and was the critical organ (3.9E-02 mGy/MBq and 4.3E-02 mGy/MBq respectively)., Conclusion: In the United States, the absorbed dose to the gallbladder would limit [C-11]-6-OH-BTA-1 administered with the approval of a Radioactive Drug Research Committee (RDRC) to a single injection of 1295 MBq (35 mCi) in the adult male, and 1314 MBq (35 mCi) in the adult female.

Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [(11)C]DASB ([(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [(11)C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry., Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183+/-5 MBq/2.3+/-1.0 nmol of [(11)C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units., Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6 x 10(-2) mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies., Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [(11)C]DASB. In the United States, the absorbed dose to the lungs would limit [(11)C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female.

11C-labeled neuroreceptor ligands frequently require long scan durations to quantify ligand-receptor binding. In this paper, we compare the accuracy of two three-dimensional (3D) positron emission tomography (PET) reconstructions: ordered-subset expectation-maximization (OS-EM) versus filtered backprojection (FBP) under low count rate conditions exhibited by 11C neuroreceptor studies. Data were obtained from a dynamic 11C phantom acquisition as well as six dynamic human [11C] WAY-100635 studies, all acquired in 3D mode using the EXACT HR+ PET scanner. Model-based scatter correction of the phantom datum was found to overcorrect in low count rate situations producing a negative bias in FBP reconstruction and a positive bias in OS-EM reconstruction, the OS-EM bias attributed to the non-negativity constraint of sinogram values. In the phantom OS-EM and FBP, reconstruction bias occurred at activities less than 25 Bq/cm3. In the human cerebellum, OS-EM deviated from FBP at activities less than 50 Bq/cm3. The total volume of distribution (VT), as determined from the metabolite corrected arterial input function and a two-tissue compartment kinetic model, was more sensitive to the positive bias of OS-EM than the negative bias of FBP at low count rates. To avoid reconstruction bias with 3D PET studies using the HR+, the scan duration should be limited so as to yield a final non-decay-corrected activity concentration of no less than 50 Bq/cm3. In neuroreceptor studies, if such a low count rate cannot be avoided, FBP reconstruction is preferable to OS-EM to estimate VT.

Objective: To determine the seroprevalence of Coxiella burnetii among the shepherds and their sheep in the lower Saint-Lawrence River region (LSLRR) of Quebec, Canada., Design: A prospective human-animal comparative study was conducted with 81 shepherds from 46 farms and a control group matched for sex and age. All participants answered a standardized questionnaire to evaluate their risk factors for Q fever, including a specific section on the work practices of the shepherds. All human subjects had a blood sample taken for serology to phase I and phase II antigens of C burnetii performed by indirect immunofluorescence assay. At each participating farm, seven to nine sheep had blood samples taken for C burnetii serology to be assessed by the complement fixation test., Results: The seroprevalence to C burnetii was higher in the group of shepherds (28.4%) than the control group (1.2%) (P<0.005). Among the group of shepherds, spending more than 5 h/week in the sheep barn (P=0.06) and buying and/or trading sheep within the past six months (P=0.004) were associated with positive C burnetii serology. A total of 137 of 334 sheep (41%) were seropositive for C burnetii. These positive sheep were distributed in 41 of the 46 flocks (89%). No correlation could be demonstrated between a serology for C burnetii in the herds and the shepherds., Conclusion: Q fever is highly prevalent in the LSLRR of Quebec, affecting 89% of the flocks and 28% of the shepherds. Shepherds in this region are at increased risk for C burnetii infection in comparison to the general population.