Improved production of Br, Br and Br via CoSe cyclotron targets and vertical dry distillation.

Introduction: The radioisotopes of bromine are uniquely suitable radiolabels for small molecule theranostic radiopharmaceuticals but are of limited availability due to production challenges. Significantly improved methods were developed for the production and radiochemical isolation of clinical quality Br, Br, and Br. The radiochemical quality of the radiobromine produced using these methods was tested through the synthesis of a novel Br-labeled inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1), a DNA damage response protein.

PET Measures of D1, D2, and DAT Binding Are Associated With Heightened Tactile Responsivity in Rhesus Macaques: Implications for Sensory Processing Disorder.

Sensory processing disorder (SPD), a developmental regulatory condition characterized by marked under- or over-responsivity to non-noxious sensory stimulation, is a common but poorly understood disorder that can profoundly affect mood, cognition, social behavior and adaptive life skills. Little is known about the etiology and neural underpinnings. Clinical research indicates that children with SPD show greater prevalence of difficulties in complex cognitive behavior including working memory, behavioral flexibility, and regulation of sensory and affective functions, which are related to prefrontal cortex (PFC), striatal, and midbrain regions.

Chemical Consequences of Radioactive Decay and their Biological Implications.

The chemical effects of radioactive decay arise from (1) transmutation, (2) formation of charged daughter nuclei, (3) recoil of the daughter nuclei, (4) electron "shakeoff" phenomenon and (5) vacancy cascade in decays via electron capture and internal conversion. This review aims to reiterate what has been known for a long time regarding the chemical consequences of radioactive decay and gives a historical perspective to the observations that led to their elucidation. The energetics of the recoil process in each decay mode is discussed in relation to the chemical bond between the decaying nucleus and the parent molecule.

Intrinsic and Stable Conjugation of Thiolated Mesoporous Silica Nanoparticles with Radioarsenic.

The development of new image-guided drug delivery tools to improve the therapeutic efficacy of chemotherapeutics remains an important goal in nanomedicine. Using labeling strategies that involve radioelements that have theranostic pairs of diagnostic positron-emitting isotopes and therapeutic electron-emitting isotopes has promise in achieving this goal and further enhancing drug performance through radiotherapeutic effects. The isotopes of radioarsenic offer such theranostic potential and would allow for the use of positron emission tomography (PET) for image-guided drug delivery studies of the arsenic-based chemotherapeutic arsenic trioxide (ATO).

High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals.

Radioisotopes of arsenic are of considerable interest to the field of nuclear medicine with unique nuclear and chemical properties making them well-suited for use in novel theranostic radiopharmaceuticals. However, progress must still be made in the production of isotopically pure radioarsenic and in its stable conjugation to biological targeting vectors. This work presents the production and irradiation of isotopically enriched (72)Ge(m) discs in an irrigation-cooled target system allowing for the production of isotopically pure (72)As with capability on the order of 10 GBq.

Mathematical modeling of positron emission tomography (PET) data to assess radiofluoride transport in living plants following petiolar administration.

Background: Ion transport is a fundamental physiological process that can be studied non-invasively in living plants with radiotracer imaging methods. Fluoride is a known phytotoxic pollutant and understanding its transport in plants after leaf absorption is of interest to those in agricultural areas near industrial sources of airborne fluoride. Here we report the novel use of a commercial, high-resolution, animal positron emission tomography (PET) scanner to trace a bolus of [(18)F]fluoride administered via bisected petioles of Brassica oleracea, an established model species, to simulate whole plant uptake of atmospheric fluoride.

Moderate-level prenatal alcohol exposure induces sex differences in dopamine d1 receptor binding in adult rhesus monkeys.

Background: We examined the effects of moderate prenatal alcohol exposure and/or prenatal stress exposure on (D1 R) binding in a non human primate model. The dopamine D1 R is involved in executive function, and it may play a role in cognitive behavioral deficits associated with prenatal alcohol and/or stress exposure. Little is known, however, about the effects of prenatal alcohol and/or stress exposure on the D1 R.

A dual-tracer study of extrastriatal 6-[18F]fluoro-m-tyrosine and 6-[18F]-fluoro-L-dopa uptake in Parkinson's disease.

6-[(18)F]-Fluoro-L-dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism--its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6-[(18)F]fluoro-m-tyrosine (FMT), which also targets L-amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol-O-methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients.

Prenatal stress induces increased striatal dopamine transporter binding in adult nonhuman primates.

Background: To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron emission tomography in rhesus monkeys (Macaca mulatta). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task).

Methods: Subjects were adult offspring derived from a 2 × 2 experiment in which pregnant monkeys were randomly assigned to control, daily mild stress exposure (acoustic startle), voluntary consumption of moderate-level alcohol, or both daily stress and alcohol.

Synthesis of [64Cu]Cu-NOTA-Bn-GE11 for PET imaging of EGFR-rich tumors.

Epidermal growth factor receptors (EGFR) are over-expressed in many different types of cancer, thus, are logical targets for both diagnosis and therapy. Antibodies and antibody fragments targeting the extracellular EGF receptor and small molecules targeting the intracellular tyrosine kinase (TK) part of EGFR have been developed as possible diagnostic EGFR imaging agents. Recently, a 12-amino acid peptide, GE11, was identified using phage display screening to have high affinity for EGFR (Kd=22nM).

A within-subject comparison of 6-[18F]fluoro-m-tyrosine and 6-[18F]fluoro-L-dopa in Parkinson's disease.

Progression of Parkinson's disease symptoms is imperfectly correlated with positron emission tomography biomarkers for dopamine biosynthetic pathways. The radiopharmaceutical 6-[(18) F]fluoro-m-tyrosine is not a substrate for catechol-O-methyltransferase and therefore has a more favorable uptake-to-background ratio than 6-[(18) F]fluoro-L-dopa. The objective of this study was to evaluate 6-[(18) F]fluoro-m-tyrosine relative to 6-[(18) F]fluoro-L-dopa with partial catechol-O-methyltransferase inhibition as a biomarker for clinical status in Parkinson's disease.

A longitudinal study of motor performance and striatal [18F]fluorodopa uptake in Parkinson's disease.

Although [(18)F]fluoro-L: -dopa [FDOPA] positron emission tomography (PET) has been used as a surrogate outcome measure in Parkinson's disease therapeutic trials, this biomarker has not been proven to reflect clinical status longitudinally. We completed a retrospective analysis of relationships between computerized sampling of motor performance, FDOPA PET, and clinical outcome scales, repeated over 4 years, in 26 Parkinson's disease (PD) patients and 11 healthy controls. Mixed effects analyses showed that movement time and tongue strength best differentiated PD from control subjects.

Assessment of fetal brain uptake of paraquat in utero using in vivo PET/CT imaging.

Prenatal in utero conditions are thought to play a role in the development of adult diseases including Parkinson's disease (PD). Paraquat is a common herbicide with chemical structure similar to 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine, a neurotoxin known to induce parkinsonism. In order to assess the role of in utero paraquat exposure in PD, uptake in maternal and fetal brains were measured using positron emission tomography (PET)/computed tomography (CT) imaging.

Production of 34m Cl and 38 Cl via the (d,α) reaction on 36 Ar and nat Ar gas at 8.4 MeV.

Production of (38)Cl and (34m)Cl via the (d, α) reaction on natural argon and (36)Ar reveal medical cyclotrons' ability to supply these isotopes in small quantities. (38)Cl provides an inexpensive developmental tool, while (34m)Cl is a positron emitter of interest in PET imaging. Production yields, cyclotron target development, cryo-recovery of enriched gases, and nucleophilic chemistry of a model compound are described.

Fetal dopamine receptor characteristics assessed in utero.

Any tracer in fetal tissue comes from maternal arterial blood. Provided steady state is achieved and intermediate compartments are reversible, the Logan graphical methods should be applicable to the assessment of binding parameters in the fetal brain. Two pregnant rhesus macaques were studied with fallypride and the Logan method was used to assess dopamine receptor distribution volume ratios (DVRs) in both maternal and fetal striatum.

Fetal dose estimates for (18)F-fluoro-L-thymidine using a pregnant monkey model.

Unlabelled: Estimating the radiation dose received by the fetus from nuclear medicine procedures is important because of the greater sensitivity of rapidly developing fetal tissues to ionizing radiation. (18)F-fluoro-L-thymidine (FLT) uptake is related to cellular proliferation and is currently used to monitor tumor progression and response to therapy. This study was undertaken to estimate-on the basis of biodistribution data obtained by PET/CT in pregnant rhesus monkeys-radiation absorbed dose to a human fetus administered (18)F-FLT.

Timing of moderate level prenatal alcohol exposure influences gene expression of sensory processing behavior in rhesus monkeys.

Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype.

Paraquat is excluded by the blood brain barrier in rhesus macaque: An in vivo pet study.

Environmental factors have long been thought to have a role in the etiology of idiopathic Parkinson's disease (PD). Since the discovery of the selective neurotoxicity of MPTP to dopamine cells, suspicion has focused on paraquat, a common herbicide with chemical structure similar to 1-methyl-4-phenylpyridinium (MPP+), the MPTP metabolite responsible for its neurotoxicity. Although in vitro evidence for paraquat neurotoxicity to dopamine cells is well established, its in vivo effects have been ambiguous because paraquat is di-cationic in plasma, which raises questions about its ability to cross the blood brain barrier.

Sensory processing disorder in a primate model: evidence from a longitudinal study of prenatal alcohol and prenatal stress effects.

Disrupted sensory processing, characterized by over- or underresponsiveness to environmental stimuli, has been reported in children with a variety of developmental disabilities. This study examined the effects of prenatal stress and moderate-level prenatal alcohol exposure on tactile sensitivity and its relationship to striatal dopamine system function in thirty-eight 5- to 7-year-old rhesus monkeys. The monkeys were from four experimental conditions: (a) prenatal alcohol exposed, (b) prenatal stress, (c) prenatal alcohol exposed + prenatal stress, and (d) sucrose controls.

Positron-emitting resin microspheres as surrogates of 90Y SIR-Spheres: a radiolabeling and stability study.

Commercially available resin microspheres and SIR-Spheres were labeled with metallic positron emitters and evaluated as positron emission tomography (PET) imaging surrogates of (90)Y SIR-Spheres. Radiolabeling was performed using a batch method, and in vitro stability over 24 h was evaluated in saline at physiological pH at 37 degrees C. The activity per microsphere distribution, as evaluated by autoradiography, showed the activity per microsphere to be proportional to the square radius of the spheres, suggesting surface binding.

Sensory processing disorders in a nonhuman primate model: evidence for occupational therapy practice.

Evaluation of sensory processing function serves as a critical component of treatment planning and implementation of intervention in pediatric occupational therapy practice. We developed a Sensory Processing Scale for Monkeys (SPS-M), based on human tests, that measures behavioral responses to a series of tactile stimuli. This assessment has been used to assess sensory processing in adult rhesus monkeys exposed to prenatal alcohol, stress, or postnatal lead.

Moderate-level prenatal alcohol exposure alters striatal dopamine system function in rhesus monkeys.

Background: Moderate prenatal alcohol exposure can cause impairments even in the absence of gross morphological defects associated with fetal alcohol syndrome. The basal ganglia, which include the dopamine-rich striatum, are sensitive to fetal alcohol-induced injury. In this study, we manipulated the timing of moderate-level alcohol exposure and compared the risk of adverse effects on striatal dopamine (DA) system function in rhesus monkeys.

Time profile of cerebral [18F]6-fluoro-L-DOPA metabolites in nonhuman primate: implications for the kinetics of therapeutic L-DOPA.

At least two rates of dopamine turnover have been demonstrated in vivo, including a slow turnover rate that is associated with synaptic vesicles, and a faster rate that leads to rapid production of dopamine metabolites. Similarly, [18F]6-fluorodopamine (FDA), the decarboxylation product of the PET tracer [18F]6-fluoro-L-DOPA (FDOPA), may have multiple turnover rates which could substantially affect the interpretation of FDOPA uptake. To better characterize FDA turnover in vivo, we measured the formation of FDOPA metabolites in primate brain following bolus FDOPA injection with carbidopa pretreatment.

PET Measurement of rCBF in the presence of a neurochemical tracer.

Functional neurochemical imaging can indicate neurotransmitter release by detecting changes in receptor occupancy. A dual tracer positron emission tomography (PET) technique is presented here to extend such studies by simultaneously measuring changes in regional cerebral blood flow (rCBF). This would permit correlations of task or drug induced changes in rCBF and neurochemical function.

Effect of tetrabenazine on the striatal uptake of exogenous L-DOPA in vivo: a PET study in young and aged rhesus monkeys.

The effect of tetrabenazine (TBZ) pretreatment on the striatal uptake of exogenous L-DOPA in vivo was assessed noninvasively in rhesus monkeys by positron emission tomography (PET) using the tracer [(18)F]-FluoroDOPA (FDOPA). Paired studies were done comparing baseline vs. TBZ treatment on the uptake of FDOPA, a measure of aromatic L-amino acid decarboxylase (AAAD) activity.