[en] The labeled serotonin agonist 3-[¹⁸F]fluoro-N-(α,α,α-trifluoro-m-tolyl)piperazine (¹⁸FTFMPP) was prepared rapidly using the labeling procedure for trifluorotoluenes, [¹⁸F]fluoro-for-nitro exchange, followed by an alumina-supported bis-alkylation. After normal-phase HPLC purification, the labeled product was obtained in 20-32% (n = 20) decay-corrected radiochemical yield with a radiochemical purity >98% and a specific activity of 100 GBq/μmol. The synthesis time including purification was 3 h. The receptor binding affinity of FTFMPP to rat brain membranes was found to be similar to that of the nonfluorinated parent compound (TFMPP). Although TFMPP has been proposed by others as an agent for the imaging of serotonin receptors, only minimal receptor-mediated uptake was observed

[en] Using positron emission tomography (PET) and nitric oxide radiolabeled with nitrogen-13 (half-life 9.97 min) we probed the distribution and kinetics of inhaled nitric oxide in anesthetized dogs. The washout of this gas after inhalation was much slower than that observed for [¹³N]nitrogen gas, demonstrating its uptake by lung tissue. The small fraction of radioactivity found in the plasma was determined to be in the form of [¹³N]nitrate. The administered gas contained < 1 ppm of nonradioactive nitric oxide, which is believed to be below the physiologic threshold for vasorelaxation

[en] Increased understanding in the area of trafficking behavior of adoptively transferred tumor-specific T cells could help develop better therapeutic protocols. We utilized the DUC18/CMS5 tumor model system in conjunction with a microPET scanner to study the DUC18 T cell distribution pattern in spleens and lymph nodes in live mice. Anti-Thy1.2 antibodies conjugated to 1,4,7,10-tetraazacyclododecane-N,N',N'',N''-tetraacetic acid (DOTA) and radiolabeled with ⁶⁴Cu were administered to three groups of BALB-Thy1.1 mice on days 4, 7, or 14 post-DUC18 T cell transfer. We were able to detect the transferred cells in all the major lymph nodes, spleens, and in tumors. Our findings suggest that tumor-specific T cells do not all preferentially localize to the tumors but they also home to all the major lymphoid organs; additionally the number of DUC18 T cells remains relatively constant during and after tumor elimination within each lymphoid organ

[en] There are several reports in the literature on the evaluation of chelates containing two nitrogens and two sulfurs (N₂S₂) as four coordinate ligands (in solution) for gallium and indium radiopharmaceuticals. No thermodynamic stability constants of these ligands were reported, and the stability of these complexes in vivo has been questioned. l,l-Ethylenedicysteine (EC) is a N₂S₂ ligand that also contains two carboxylic acid moieties for complexation of Ga(III) and In(III) in a hexacoordinate environment. The stability constants of Ga- and In-EC have been determined by potentiometric methods. The stability of In-EC was found to be greater than that of Ga-EC, with stability constants (log K's) of 33.0 and 31.5, respectively. A molecular mechanics evaluation of the Ga- and In-EC complexes support the thermodynamic results. ⁶⁷Ga- and ¹¹¹In-labeled complexes of EC were prepared and analyzed by thin layer chromatography and electrophoresis. Both complexes were evaluated in biodistribution studies in normal Sprague-Dawley rats. ¹¹¹In-EC cleared rapidly through the hepatobiliary system, whereas ⁶⁷Ga-EC remained in the liver at 1 h post-injection. Although ⁶⁷Ga-EC was retained in the liver, suggesting instability of the complex in vivo, ⁶⁷Ga-EC was stable in rat plasma in vivo at 2 h post-injection. Because of the high thermodynamic and in vivo stability of In-EC, derivatives of EC may have applications as bifunctional chelates for ¹¹¹In-labeled proteins and peptides. More lipophilic analogues of ⁶⁸Ga-EC may also have potential as myocardial PET imaging agents

[en] Deflection by magnetic or electric field gradients has long been used to analyze or to alter the translational trajectories of neutral gas-phase atoms or molecules. Recent work has developed sources of slow, cold molecular beams that offer means to enhance markedly the attainable deflections, which are inversely proportional to the translational kinetic energy. The sensitivity and resolution can thus be much increased, typically by factors of 10²-10⁴. We illustrate ways to exploit this enhanced deflection capability, particularly when balancing electric and magnetic deflections. Chemical scope can be greatly extended by utilizing feeble but ubiquitous interactions, especially the induced electric dipole due to the molecular polarizability and magnetic moments resulting from molecular rotation or nuclear spins. We also examine the effect of non-Maxwellian velocity distributions produced by supersonic expansions or by quantum statistics (pertinent for ultracold beams). Generic plots are provided, employing dimensionless variables, to facilitate the design and interpretation of experiments with deflections amplified by low kinetic energy

No abstract available

[en] The positron emitting radionuclides, oxygen-15, nitrogen-13, carbon-11, and fluorine-18 have been produced at Washington University for many years utilizing two biomedical cyclotrons; a Cyclotron Corporation CS15 and a Japan Steel Works 16/8 cyclotron. In recent years we have become interested in the production of non-standard PET isotopes. We were initially interested in copper-64 production using the ⁶⁴Ni(p,n)⁶⁴Cu nuclear reaction, but now apply this technique to other positron emitting copper isotopes, copper-60 and copper-61. Copper-64 is being produced routinely and made available to other institutions. In 1999 over ten Curies of copper-64 were produced, making copper available to thirteen institutions, as well as research groups at Washington University. We are currently developing methods for the routine productions of other PET radioisotopes of interest, these include; bromine-76, bromine-77, iodine-124, gallium-66, and technetium-94m

[en] The serotonin 5-HT_1B receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [¹¹C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT_1B receptor. [¹¹C]P943 was synthesized via N-methylation of the precursor with [¹¹C]methyl iodide or [¹¹C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8±3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BP_ND) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT_1B receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BP_ND values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT_1B/5-HT_1D antagonist, resulted in reduction of BP_ND values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [¹¹C]P943 for 5-HT_1B receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT_1B receptor system in humans.

[en] [¹⁸F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test-retest reproducibility of [¹⁸F]FPEB in the human brain. Seven healthy male subjects were scanned twice, 3 - 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [¹⁸F]FPEB. Four methods were used to estimate volume of distribution (V_T): equilibrium analysis (EQ) using arterial (EQ_A) or venous input data (EQ_V), MA1, and a two-tissue compartment model (2 T). Binding potential (BP_ND) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test-retest variability (aTRV) of V_T and BP_ND were calculated for each method. Venous blood measurements (C_V) were compared with arterial input (C_A) to examine their usability in EQ analysis. Regional V_T estimated by the four methods displayed a high degree of agreement (r² ranging from 0.83 to 0.99 among the methods), although EQ_A and EQ_V overestimated V_T by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V_T were 11 % by EQ_A, 12 % by EQ_V, 14 % by MA1 and 14 % by 2 T. Regional BP_ND also agreed well among the methods and mean aTRV of BP_ND was 8 - 12 % (CWM) and 7 - 9 % (CGM). Venous and arterial blood concentrations of [¹⁸F]FPEB were well matched during equilibrium (C_V = 1.01 . C_A, r² = 0.95). [¹⁸F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [¹⁸F]FPEB is an excellent PET imaging tracer for mGluR5 in humans. (orig.)

[en] This study was designed as ''proof of concept'' for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses to molecularly targeted therapy. Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6-8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6 or 7) with [¹⁸F]fluorodeoxyglucose, [¹⁸F]fluoro-L-thymidine, [¹⁸F]fluoro-azoazomycinarabinoside or [¹⁸F]fluoromisonidazole. Separate cohorts (n=3) were treated identically and tumours were assessed ex vivo for markers of glucose metabolism, proliferation and hypoxia. During the study period, mean uptake of all PET tracers generally increased for control tumours compared to baseline. In contrast, tracer uptake into CI-1033-treated tumours decreased by 20-60% during treatment. Expression of the glucose transporter Glut-1 and cell cycle markers was unchanged or increased in control tumours and generally decreased with CI-1033 treatment, compared to baseline. Thymidine kinase activity was reduced in all tumours compared to baseline at day 3 but was sevenfold higher in control versus CI-1033-treated tumours by day 6 of treatment. Uptake of the hypoxia marker pimonidazole was stable in control tumours but was severely reduced following 7 days of CI-1033 treatment. CI-1033 treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET. The PET findings correlated well with ex vivo biomarkers for each of the cellular processes studied. These results confirm the utility of small animal PET for evaluation of the effectiveness of molecularly targeted therapies and simultaneously definition of specific cellular processes involved in the therapeutic response. (orig.)