Elevated sympathetic nervous system (SNS) tone contributes to excess cardiac mortality associated with type 2 diabetes mellitus (T2DM). Chronic SNS stimulation has detrimental effects to the heart, in particular, with its cell signaling abilities. (R)-[11C]Rolipram small animal positron emission tomography (PET), an noninvasive nuclear imaging modality, was used to assess phosphodiesterase-4 (PDE4) alterations in a high fat diet (HFD), streptozotocin (STZ) induced model of hyperglycemia in rats. Prior to investigation in the animal model, characterization of (R)-[11C]rolipram small animal PET was completed. (R)-[11C]Rolipram binds specifically to PDE4 in the rat heart demonstrated by competitive blockade with (R)-rolipram with the PDE4 enzyme susceptible to saturation with increasing injected masses of unlabeled rolipram. (R)-[11C]Rolipram cardiac retention was elevated by acute norepinephrine stimulation via desipramine pharmacologic challenge. Quantitative (R)-[11C]rolipram PET was highly reproducible in the heart and presents an ideal avenue to investigate PDE4 alterations. (R)-[11C]rolipram small animal PET did not reveal changes in PDE4 expression and activity in STZ-treated hyperglycemic animals compared to STZ-treated euglycemic and control groups. In vitro measures of PDE4 enzyme expression and activity, with or without desipramine, were also not altered between treatment groups. Although (R)-[11C]rolipram small animal PET does not reveal PDE4 alterations in this animal model of diabetes, its utility to assess PDE4 alterations in other over active SNS pathologies, such as heart failure and obesity, remains.

Environmental stimuli associated with drug use are related to drug craving and relapse. The mechanism of cue-induced craving is thought to involve the release of dopamine (DA) in brain regions associated with reward and habit formation. The aim of the study was to investigate the role of DA in cue-induced craving in tobacco-dependent smokers using Positron Emission Tomography (PET) and a picture cue paradigm. Tobacco-associated cues were capable of eliciting significantly greater subjective reports of craving relative to neutral cues in tobacco smokers (n=6) in a neuroimaging environment. Using this cue paradigm and [11C]-(+)-PHNO PET (n=6), a non-significant trend towards a greater decrease in binding potential, indicative of dopamine release, was shown in selected brain regions of interest. These findings are similar to findings in cocaine-dependent individuals and suggest the involvement of dopamine in the response to smoking-associated cues in tobacco-dependent individuals.

Elevated sympathetic nervous system (SNS) tone contributes to excess cardiac mortality associated with type 2 diabetes mellitus (T2DM). Chronic SNS stimulation has detrimental effects to the heart, in particular, with its cell signaling abilities. (R)-[11C]Rolipram small animal positron emission tomography (PET), an noninvasive nuclear imaging modality, was used to assess phosphodiesterase-4 (PDE4) alterations in a high fat diet (HFD), streptozotocin (STZ) induced model of hyperglycemia in rats. Prior to investigation in the animal model, characterization of (R)-[11C]rolipram small animal PET was completed. (R)-[11C]Rolipram binds specifically to PDE4 in the rat heart demonstrated by competitive blockade with (R)-rolipram with the PDE4 enzyme susceptible to saturation with increasing injected masses of unlabeled rolipram. (R)-[11C]Rolipram cardiac retention was elevated by acute norepinephrine stimulation via desipramine pharmacologic challenge. Quantitative (R)-[11C]rolipram PET was highly reproducible in the heart and presents an ideal avenue to investigate PDE4 alterations. (R)-[11C]rolipram small animal PET did not reveal changes in PDE4 expression and activity in STZ-treated hyperglycemic animals compared to STZ-treated euglycemic and control groups. In vitro measures of PDE4 enzyme expression and activity, with or without desipramine, were also not altered between treatment groups. Although (R)-[11C]rolipram small animal PET does not reveal PDE4 alterations in this animal model of diabetes, its utility to assess PDE4 alterations in other over active SNS pathologies, such as heart failure and obesity, remains.

Les opioïdes peuvent être responsables, en cas d’intoxication, d’une dépression respiratoire mortelle. Deux opioïdes ont un profil de toxicité particulier. La buprénorphine, seule, a des effets respiratoires plafonnés alors qu’administrée avec des benzodiazépines elle peut être à l’origine d’une dépression respiratoire mortelle. Le tramadol, dans un contexte d’intoxication aigue, entraine dans 20% des cas des convulsions. Les mécanismes de ces toxicités sont inconnus.L’objectif de cette thèse était d’étudier de façon multimodale les mécanismes impliqués dans ces deux types de toxicité en incluant des données pharmacodynamiques et neuropharmacocinétiques in vivo. Pour la buprénorphine, nous avons montré que la dépression respiratoire observée avec le diazépam ne résultait pas d’une interaction neuropharmacocinétique/réceptologique centrale (imagerie TEP 11C- buprénorphine). En revanche, les données physiologiques respiratoires (pléthysmographie, gaz du sang, électromyographie) et leur réversion par les antagonistes des récepteurs opioïdes et de l’acide γ-aminobutyrique (GABA) étaient en faveur d’une interaction pharmacodynamique. Pour le tramadol, nous avons montré que les convulsions n’impliquaient pas les systèmes noradrénergiques, dopaminergiques, sérotoninergiques ou opioïdergiques. Le tramadol agissait comme un modulateur allostérique négatif du site de liaison des benzodiazépines des récepteurs GABA-A (imagerie TEP 11C-flumazénil). Par cette approche multimodale in vivo chez le rat, nous avons pu déterminer que les interactions entre les opioïdes et le système GABAergique jouent un rôle majeur dans les profils de toxicité spécifique de la buprénorphine et du tramadol. / Opioids overdose may be responsible for respiratory depression. Nevertheless, two molecules exhibit particular toxicity patterns. Buprenorphine induces ceiling respiratory effects even at high doses. However, several deaths have been reported, mainly when buprenorphine was co-administered with benzodiazepines. Tramadol is a µ-opioid receptor agonist that induces seizures in 20% of poisoning cases. The exact mechanisms involved in both toxicity remain poorly understood. The aim of our investigation was to study the mechanisms involved in these two types of toxicity using a multimodal approach including pharmacodynamic data and in vivo brain neuropharmacokinetics. Regarding buprenorphine, we have shown that respiratory depression with diazepam does not result from neuropharmacokinetic/receptologic interaction (11C-buprenorphine PET imaging) Conversely, the study of respiratory parameters (plethysmography, blood gas, electromyogram) and their antagonization by opioid and gamma-aminobutyric acid (GABA) receptors antagonists supported interactions mediated by the addition of the pharmacodynamic effects of each molecule. Regarding tramadol, we showed that seizures did not involve the noradrenergic, dopaminergic, serotoninergic or opioidergic systems. Conversely, they involve the GABA-ergic system; tramadol acts as negative allosteric modulator of the benzodiazepine site of the GABA-A receptor (11C-flumazenil PET imaging). Using a multimodal in vivo approach in the rat, we have been able to determine that the interactions between opioids and the GABAergic system play a major role in mechanisms of toxicity of buprenorphine and tramadol.

This work deals with radiochemistry and new approaches to develop novel PET tracers labelled with the radionuclide 11C. Two methods for the synthesis of 11C-labelled acrylamides have been explored. First, [1-11C]-acrylic acid was obtained from a palladium(0)-mediated 11C-carboxylation of acetylene with [11C]carbon monoxide; this could be converted to the corresponding acyl chloride and then combined with benzylamine to form N-benzyl[carbonyl-11C]acrylamide. In the second method, the palladium(0)-mediated carbonylation of vinyl halides with [11C]carbon monoxide was explored. This latter method, yielded labelled acrylamides in a single step with retention of configuration at the C=C double bond, and required less amine compared to the acetylene method. The vinyl halide method was used to synthesize a library of 11C-labelled EGFr-inhibitors in 7-61% decay corrected radiochemical yield via a combinatorial approach. The compounds were designed to target either the active or the inactive form of EGFr, following computational docking studies. The rhodium(I)-mediated carbonylative cross-coupling of an azide and an amine was shown to be a very general reaction and was used to synthesize a library of dual VEGFr-2/PDGFrβ inhibitors that were 11C-labelled at the urea position in 38-78% dc rcy. The angiotensin II AT1 receptor antagonist eprosartan was 11C-labelled at one of the carboxyl groups in one step using a palladium(0)-mediated carboxylation. Autoradiography shows specific binding in rat kidney, lung and adrenal cortex, and organ distribution shows a high accumulation in the intestines, kidneys and liver. Specific binding in frozen sections of human adrenal incidentalomas warrants further investigations of this tracer. Three angiotensin II AT2 ligands were 11C-labelled at the amide group in a palladium(0)-mediated aminocarbonylation in 16-36% dc rcy. One of the compounds was evaluated using in vitro using autoradiography, and in vivo using organ distribution and animal PET. The compound was metabolized fast and excreted via urine. High radioactivity was also found in the liver, meaning that more metabolically stable compounds are desirable for future development.

Introduction Since its development by Al Wolf and colleagues in the 1970s1, [11C]cyanide has been a useful synthon for a wide variety of reactions, most notably those producing [1-11C]-labeled amino acids2. However, despite its position as rote gas-phase product, the catalytic synthesis is difficult to optimize and often only perfunctorily dis-cussed in the radiochemical literature. Recently, [11C]CN– has been used in the synthesis of indole-3-[1-11C]acetic acid ([11C]IAA), the principal phytohormone responsible for a wide variety of growth and development functions in plants3. The University of Wisconsin has expertise in cyclotron production and radiochemistry of 11C and previous experience in the PET imaging of plants4,5. In this abstract, we present work on optimizing [11C]CN– production for the synthesis of [11C]IAA and the PET imaging of auxin transport in living plants. Material and Methods [11C]CH4 was produced by irradiating 270 psi of 90% N2, 10% H2 with 30 µA of 16.1 MeV protons from a GE PETtrace cyclotron. After irradiation, the [11C]CH4 was converted to [11C]CN– by passing through a quartz tube containing 3.0 g of Pt wire and powder between quartz wool frits inside a 800–1000 ˚C Carbolite tube furnace. The constituents and flow rate of the [11C]CH4 carrier gas were varied in an effort to optimize the oven\'s catalytic production of [11C]CN– from CH4 and NH3. The following conditions were investigated: i. Directly flowing irradiated target gas versus trapping, purging and releasing [11C]CH4 from a −178 ˚C HayeSep D column in He through the Pt furnace. ii. Varying the amount of anhydrous NH3 (99.995%) mixed with the [11C]CH4 carrier gas prior to the Pt furnace. Amounts varied from zero to 35 % of gas flow. iii. Varying the purity of the added NH3 gas with the addition of a hydride gas purifier (Entegris model 35KF), reducing O2 and H2O impurities to < 12 ppb. iv. Varying the flow rate of He gas carrying trapped, purged and released [11C]CH4. After flowing through the Pt furnace, the gas stream was bubbled through 300 µL of DMSO containing IAA precursor gramine (1 mg), then passed through a 60×5 cm column containing ascarite to absorb [11C]CO2, followed by a −178˚C Porapak Q column to trap [11C]CH4 and [11C]CO. After bubbling, the DMSO/gramine vial was heated to 140 ˚C to react the gramine with [11C]CN–, forming the intermediate indole-3-[1-11C]acetonitrile ([11C]IAN), which was subsequently purified by solid phase extraction (SPE). The reaction mixture was diluted into 20 mL water and loaded onto a Waters Sep-Pak light C18 cartridge, followed by rinsing with 5 mL of 0.1% HCl : acetonitrile (99 : 1) and 10 mL of the same mixture in ratio 95 : 5, and finally eluted with 0.5 mL of diethyl ether. The ether was subsequently evaporated under argon flow, followed by the hydrolysis of [11C]IAN to [11C]IAA with the addition of 300 µL 1 M NaOH and heating to 140 ˚C for 5 minutes. After hydrolysis, the solution was neutralized with 300 µL 1 M HCl and purified using preparative high-performance liquid chromatography (HPLC) using a Phenomenex Luna C18 (10μ, 250×10mm) column with a mobile phase acetonitrile : 0.1% formic acid in H2O (35 : 65) at flow rate of 3 mL/min. The [11C]IAA peak, eluting at 12 minutes, was collected and rotary evaporated to dryness, then again after the addition of 5 mL acetonitrile, followed by its reconstitution in 50 µL of water. Analytical HPLC was performed on the [11C]IAA before and after this evaporation procedure using a Phenomenex Kinetex C18 (2.6μ, 75× 4.6 mm) column with a linear gradient elution over 20 minutes of 10 : 90–30 : 70 (acetonitrile : 0.1% formic acid) at a 1 mL/min flow rate, eluting at 7.6 minutes. The transport of [11C]IAA was monitored following administration through the severed petiole of rapid cycling Brassica oleracea (rcBo) using a Siemens microPET P4 scanner. Transport was compared following administration to the first true leaf versus the final fully formed leaf in plants with and without exposure to the polar auxin transport inhibitor naphthylphthalamic acid (NPA). Results and Conclusion Optimization of the [11C]CN– gas phase chemistry was performed using two key metrics for measuring conversion yield. First is the fraction of total produced radioactivity that trapped in the DMSO/gramine solution (denoted %DMSO), and second, the fraction of DMSO/gramine-trapped activity that was able to react with gramine to form [11C]IAN (denoted %CN–). Under certain conditions, the former of these metrics experienced significant losses due to unconverted [11C]CH4 or through combustion, forming [11C]CO2 or [11C]CO. The latter metric experienced losses due to production of incomplete oxidation products of the CH4-NH3 reaction, such as methylamine. Total [11C]CH4 to [11C]CN– con-version yields is reported by the product of the two metrics. It was initially hypothesized that the irradiation of a 90% N2, 10% H2 target gas would produce sufficient in-target-hot-atom-produced NH3 to convert [11C]CH4 to [11C]CN– in the Pt furnace. However, conversion yields were found to be low and highly variable, with 13 ± 8 % trapping in DMSO/gramine, 9 ± 9 % of which reacted as CN– (n = 15). While in disagreement with previous reports1, this is likely as a result the batch irradiation conditions resulting ammonia losses in the target chamber and along the tubing walls. Yields and reproducibility were improved when combining the target gas with a stream of anhydrous NH3 gas flow with conversion yields reported in TABLE 1. However, these yields remained undesirably low, potentially as a result of the 10% H2 carrier gas having an adverse effect on the oxidative conversion of [11C]CH4 to [11C]CN–. To remedy this, the irradiated target gas was trapped, purged, released in He and combined with NH3 gas before flowing through the Pt furnace. Initial experiments using 99.995% anhydrous NH3 gas resulted in very poor (< 0.1%) [11C]CN– yields as a result of nearly quantitative combustion forming [11C]CO2. Installation of a hydride gas purifier to reduce O2 and H2O impurities in NH3 improved yields for CH4 in He, but did not significantly affect those from [11C]CH4 in N2/H2 target gas. In disagreement with previous reports2, conversion yields were found to be highly sensitive to overall carrier gas flow rate, with lower flow rates giving the best yields, as shown in TABLE 1. Optimization experiments are continuing. The total decay-corrected yield for the 1 hour synthesis of [11C]IAA in 50 µL of water is 2.3 ± 0.7 %, based on the total produced [11C]CH4 with a specific activity ranging from 1–100 GBq/µmol. The principal radiochemical impurity was determined to be indole-3-carboxylic acid. The SPE procedure isolating the [11C]IAN intermediate product was optimized to minimize this impurity in the final sample. After a rapid distribution of the administered [11C]IAA through the cut petiole and throughout the rcBO plant, upward vascular transport of auxin and downward polar auxin transport was visualized through time-activity curves (TACs) of regions of interest along the shoot. Comparison of these TACS with and without exposure to NPA yields insight into the fundamental physiological process of polar auxin transport in plants. In conclusion, the Pt-catalyzed oxidative conversion of [11C]CH4 and NH3 to [11C]CN– is a challenging process to optimize and highly sensitive to carrier gas composition and flow rate. Optimization for our experimental conditions yielded several results which disagreed with previous reports. [11C]IAA produced using [11C]CN– is well suited for PET imaging of polar auxin transport in living plants.

Introduction [11C]choline is a very effective PET radiopharma-ceutical for the study of prostate cancer. To support the increasing demand for [11C]choline, several different synthetic approaches have been described in the literature, including different automated production methods using remote-controlled synthesis modules [1–4]. The most popular method uses a C18 Sep-Pak as solid support for methylation and, subsequently, a CM Sep-Pak for purification [2]. We report an optimized method for producing [11C]choline using only one CM Sep-Pak for both reaction and purification as was shown in the literature [4]. For synthesis of [11C]choline we used two modules Tracerlab FXC for preparation of methylation reagent [11C]CH3I and GPF-101 for [11C]choline synthesis. Material and Methods TracerlabFXC GE, GPF-101 Veenstra Instrument, 2-(dimethylamino)-ethanol (DMAE) ABX, Sep-Pak Light Accell Plus CM cation-exchange cartridges Waters used without conditioning, precursor 50 µL of DMAE dissolved in 25 µL of ethanol and loaded on a CM Sep-Pak. Schematic diagram of the automated system for the production of [11C]choline is given below. [11C]CH4 was produced in two standard Nitra target IBA irradiation of mixture 90 % N2/10 % H2 with 15 MeV protons using dual beam. Results and Conclusion [11C]CH4 was prepared in the targets and connected with Tracerlab FXC. [11C]CH3I was pre-pared in a loop in which allowed to react of elemental iodine at a temperature 720 oC. Con-version to [11C]CH3I usually is around 50% uncorrected activity. Activity is within the range 15–18 GBq of [11C]CH3I and time of production 10 min. Synthesis of [11C]choline is based on the reaction DMAE with [11C]CH3I on a Accell Plus CM cation-exchange column which serves both as a support for reaction and for separation of choline from DMAE by ethanol washing. The basic parameters are shown in TABLE 1. Beam current 2X 20 µA Irradiation time 30 min DMAE 50 µl Synthesis time from EOB 25 min Absolute yield without correction 6.6 GBq Radiochemical purity > 99 % Residual DMAE in product < 5 ppm Ethanol < 1000 mg/L pH 4.5–8.5 TABLE 1. Reaction parameters and result of production of [11C]choline syntheses Conclusion We have applied a simple synthesis method for [11C]choline preparation using automated commercial equipments with one column used both for reaction and separation purpose. The main advantage of using one column is lower contamination of the product [11C]choline with DMAE. When for synthesis of [11C]choline two columns C18 for synthesis and CM for separation is used, higher contamination of DMAE can be found in the product due to a release of DMAE from C18 column.

Introduction Recently in our laboratory we needed a reliable and relatively simple source of aqueous solutions of [11C]CO2. We examined various methods of trapping [11C]CO2 gas both in solution and on ion exchange resins, followed by elution into aqueous phase. We favor simple methods that have high trapping and elution efficiencies and produce a highly concentrated solution. Furthermore, we desired methods that would minimize the use of hazardous reagents and materials with respect to both handling and disposal. We also considered the formulation of the final solution in terms of chemical compatibility with contacted materials, working with the assumption that dilute bicarbonate or carbonate solutions will have little reactivity with many materials. In a phantom, compatibility with materials (i.e. plastics, glues, metals, etc.) is important (1-4), while in (bio)geochemical studies – where transport of carbon is important – the chemical form of the radiolabelled molecule is important, but compatibility must be determined on a case-by-case basis (5-7). Small medical cyclotrons can easily produce carbon-11 as gaseous [11C]CO2, and various methods are utilized to incorporate carbon-11 into solution, often with unfavorable resource requirements, costs, or chemical properties. Commonly [11C]CO2 gas is bubbled through a strong base, forming the carbonate anion; but neutralizing a strong base (as to avoid special handling or disposal requirements) requires a large volume of diluent or buffer; or a very precise addition of acid – which if done improperly – may lead to an acidic pH and subsequent loss of [11C]CO2 from solution (8,9). Alternatively, [11C]CO2 (or [11C]CH4) can be converted to [11C]CH3I at high-yield, but requires specialized, expensive radio-synthesis equipment (10-12). [11C]CH3I can then be trapped in DMSO (albeit providing a volatile and hazardous solution) or used as a synthon en route to water soluble compounds such as [11C]choline (13). Finally, leftover radiolabelled radiopharmaceuticals from a carbon-11 imaging experiment could be used, but chemical compatibility (i.e. lipophilicity) of the radiolabelled compound may be of concern. Carbon dioxide gas will dissolve with a solubility of 1.5 g/L at STP (9) and slowly react with water to generate carbonic acid (H2CO3), a weak acid. Passing [11C]CO2 through a base-activated ion exchange cartridge, the [11C]CO2 reacts with hydroxide ions to form [11C]carbonate which is bound to the resin due to its higher selectivity for carbonate than hydroxide (14). Elution with excess bicarbonate displaces [11C]carbonate and neutralizes any remaining hydroxide, providing a 11C aqueous solution that is mildly basic, chemically non-hazardous, and very concentrated. Material and Methods [11C]CO2 gas trapping efficiency was evaluated for solutions and base-activated ion exchange resins. The gas was delivered either rapidly in a high-flow bolus directly from the cyclotron target or slowly in a low-flow helium stream during heating of a carbosieves column. Elution efficiency of ion exchange cartridges were evaluated for both fraction of trapped activity eluted and volume of solution needed for elution. [11C]CO2 was produced via the 14N(p,α)11C reaction on a CTI RDS111 – 11 MeV cyclotron at the Lawrence Berkeley National Laboratory’s Bio-medical Isotope Facility. The 7 mL target is pressurized to 315 psi with 1% O2/N2 gas, equating to 150 mL gas at STP. For direct-from-target trapping experiments, the target was decompressed and routed to the cartridge via 50 feet of 0.020” I.D. tubing until the target falls to atmospheric pressure (~55 seconds) providing an inhomogeneous flow – a short rapid burst of flow followed by a longer low-flow bleed. For helium-eluted experiments, the [11C]CO2 was unloaded from the cyclotron target and trapped on a room-temperature carbosieves column (15). Target gases were subsequently flushed from the column for 30 seconds with helium at 50 mL/min. After heating the column to 125 °C without gas flow, [11C]CO2 was eluted off the column in helium at 15 mL/min. [11C]CO2/He was bubbled through 9 aqueous and 2 organic solutions to test for trapping efficiency in a slow, steady helium stream at 15 mL/min (sodium hydroxide (0.96M, 0.096M, 0.0096M), sodium bicarbonate (1.14M, 0.57M, 0.057M), sodium carbonate (2.0M, 1.0M, 0.10M), ethanol, and DMSO (2mL ea.). An Ascarite-filled cartridge was attached to trap any untrapped [11C]CO2. Measures of radioactivity were made using a Capintec CRC-15R dose calibrator. Trapping efficiency for solutions is calculated as the fraction of radioactivity captured in solution relative to the sum of the solution and the Ascarite trap. Three different commercially available, ion ex-change cartridges were evaluated for trapping and elution efficiencies. FIGURE 1 shows a photo-graphic comparison of the physical size and shapes of the cartridges as well as a X-ray computed tomography (CT) cross sectional view of the internal ion exchange resin volume and dead volume of the cartridges. All cartridges were activated with 1 mL of 1 N aqueous NaOH followed by passing 10 mL deionized water then 10 mL of air through the cartridge. In both direct-from-target (n = 4) and helium-stream experiments (n = 3 or 4), cartridges were connected to [11C]CO2 delivery lines via Luer connections. The gas exiting the cartridge passed through an empty 3 mL crimp-top vial as a liquid trap en route to an Ascarite trap on the vent needle as described above. Trapping efficiency for cartridges is calculated as the fraction of radioactivity captured on the cartridge relative to the sum of the cartridge, the empty vial, and the Ascarite trap. Cartridges were eluted with 0.5 mL of saturated sodium bicarbonate solution (1.14 M @ 20°C) followed by 9.5 mL water and 10 mL air. Elution efficiency is calculated as the fraction of radioactivity eluted in 10 mL relative to the sum of the spent cartridge following elution and the 10 mL eluate (Equation 5). The pH of the eluate was measured using 0-14 pH test strips. Results and Conclusion The trapping of [11C]CO2 in all solutions was less than 70% of the total radioactivity with the exception of the 0.96 M and 0.096 M NaOH. With a higher concentration of base driving equilibrium towards carbonate stability, it could be expected that the most basic solution had the best trapping efficiency, but this attribute also means it is least desirable solution to work with from a hazardous material or chemical compatibility perspective. When [11C]CO2 was delivered in a helium stream, all three cartridges performed at near 100% efficiency, as shown in FIGURE 4. With higher flow, direct-from-target delivery, the cartridges trapped [11C]CO2 with a wider range of efficiencies: ICOH (99 ± 1 %), ORTG (90 ± 2 %), and QMA (79 ± 4 %). Elution resulted in > 99 % release of carbon-11 activity for both QMA and ORTG cartridges, but only 39 ± 3 % release from the ICOH cartridge. Elution efficiency of the trapped radioactivity (Equation 5) was independent of the method of [11C]CO2 delivery. Across all cartridges and delivery methods, the eluate was at about pH = 10. We recommend that the ORTG cartridge be used for trapping of [11C]CO2 gas with elution by > 300 µL of saturated bicarbonate solution. This recommendation is based on the better trapping for ORTG cartridges compared to the QMA cartridges in the direct-from-target [11C]CO2 delivery method and the smaller volume needed for elution of all trapped carbon. This method excels based on its simplicity, adaptability to automation, low-cost ($5/cartridge), and observations that a single ORTG cartridge suffers no loss of performance after multiple uses. A potential disadvantage to this method is that it involves using a carbon-containing eluent, which means that this method cannot be used for imaging experiments that require high specific activity. However, considering the eluate is a mildly basic aqueous solution, we expect that it will be compatible with a wide variety of materials and experimental applications.

Introduction High starting radioactivity is usually advantageous for producing radiopharmaceuticals with high specific radioactivity. However, the [11C]CH4 yields from N2-H2 gas target fall short from theoretical amounts, as calculated from the cross section for the well-known 14N(p,α)11C nuclear reaction1. The beneficial effect of increased target chamber temperature on [11C]CH4 yields has recently been brought forward by us2 and others3. In addition to the temperature effect, our attention has also been on the hydrogen content factor. This study intends to examine the N2-H2 target performance in a substantially larger target chamber and at higher temperatures than our setup before and compare the results to the existing data. Materials and Methods Aluminium bodied custom design target chamber is used in fixed 17 MeV proton beam irradiations. Target chamber is equipped with heating elements and cooling circuit for temperature control. In addition to the target chamber body temperature, the target gas loading pressure and irradiation current can be varied. The irradiation product is collected into an ad-sorbent trap that was immersed in a liquid argon cooling bath within a dose calibrator. Results and Conclusion Pursued data will show [11C]CH4 saturation yields (Ysat [GBq/µA]) at different irradiation and target parameters.

Introduction At WTTC 14 we presented data on the target yields of our GE PETtrace C-11 HP target in comparison to the target yields we had been getting on the MC17 prior to its decommissioning1. Discussion with other attendees alerted us to the fact that the target may be too “thin”, allowing the beam to spread out and interact with the walls, which could result in a lower target yield. Additionally, a GE service engineer indicated that we could be striking the top of the target with some of the beam, due both to target thinning and the “banana” effect from the magnetic fringe fields. Experiments were carried out to determine the potential magnitude of this effect and the efficacy of potential solutions. Material and Methods All experiments were performed on a GE PET-trace cyclotron. The first set of experiments was performed on the C-11 HP target in its natural mounting state (no aids). The change is gas pressure as a function of beam current was measured, from 5 to 70 microamps for three different gas fill pressures: 210, 230 and 250 PSI. The second set of experiments was performed after mechanically lifting the back end of the target with a box, changing the target angle from 23.9 degrees past horizontal to 25.2 degrees past horizontal. While this change in angle does not seem drastic, it did pick up all the slack in the target mount due the sagging of the target from its longer length than other GE targets. The change in gas pressure as a function of beam current was measured, from 5 to 80 microamps for four different gas fill pressures: 190, 210, 230 and 250 PSI. (Note that the box is a temporary solution and the target will sag over time without a more permanent solution for supporting the back end of the target.) Results and Conclusion The graphical results of pressure rise as a function of beam current are shown in FIGURE 1. Note that measurements were stopped when the pressure approached 470 PSI, based on advice from GE engineers. There is some flattening out for the 190-PSI data, even with the increase in angle as an attempt to counteract the banana effect (note that GE’s recommended fill pressure is 187 PSI). Increases in the fill pressure helped in keeping the target thick, but with the tradeoff that less beam can be put onto the target before reaching the maximum specified pressure. Final-ly, using a lifting mechanism to raise the back of the target also helped to prevent thinning, as seen in the r-squared values for the linear fit, shown in TABLE 1. The data presented indicate that a shorter target that can withstand higher pressures could be beneficial for the PETtrace cyclotron, allowing the beam to fully stop before striking the walls, be it through target thinning or the “banana” effect while still allowing the user to run high beam currents.