@article{WenzArndtSamnick2022, author = {Wenz, Jan and Arndt, Felix and Samnick, Samuel}, title = {A new concept for the production of \(^{11}\)C-labelled radiotracers}, series = {EJNMMI Radiopharmacy and Chemistry}, volume = {7}, journal = {EJNMMI Radiopharmacy and Chemistry}, doi = {10.1186/s41181-022-00159-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300731}, year = {2022}, abstract = {Background The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this "plug 'n' synthesize" principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate. Results The target gas purification of cyclotron produced [\(^{11}\)C]CO\(_2\) and subsequent conversion to [\(^{11}\)C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[\(^{11}\)C]choline and L-S-methyl-[\(^{11}\)C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [\(^{11}\)C]MeI. After 18 min N-methyl-[\(^{11}\)C]choline was isolated with 52\% decay corrected yield and a radiochemical purity of > 99\%. For L-S-methyl-[\(^{11}\)C]methionine the total reaction time was 19 min reaction, yielding 25\% of pure product (> 97\%). The reactor design was used as an exemplary model for the technically challenging [\(^{11}\)C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [\(^{11}\)C]CO\(_2\) was passed through. After complete release of [\(^{11}\)C]CO\(_2\) the reaction mixture was quenched with water and guided through a series of ion exchangers (H\(^+\), Ag\(^+\) and OH\(^-\)). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [\(^{11}\)C]CO\(_2\) before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [\(^{11}\)C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5\%. Conclusion Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[\(^{11}\)C]choline, L-S-methyl-[\(^{11}\)C]methionine and [11C]acetate.}, language = {en} } @article{OsmanogluKhaledAlSeiariAlKhoorietal.2021, author = {Osmanoglu, {\"O}zge and Khaled AlSeiari, Mariam and AlKhoori, Hasa Abduljaleel and Shams, Shabana and Bencurova, Elena and Dandekar, Thomas and Naseem, Muhammad}, title = {Topological Analysis of the Carbon-Concentrating CETCH Cycle and a Photorespiratory Bypass Reveals Boosted CO\(_2\)-Sequestration by Plants}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {9}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2021.708417}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249260}, year = {2021}, abstract = {Synthetically designed alternative photorespiratory pathways increase the biomass of tobacco and rice plants. Likewise, some in planta-tested synthetic carbon-concentrating cycles (CCCs) hold promise to increase plant biomass while diminishing atmospheric carbon dioxide burden. Taking these individual contributions into account, we hypothesize that the integration of bypasses and CCCs will further increase plant productivity. To test this in silico, we reconstructed a metabolic model by integrating photorespiration and photosynthesis with the synthetically designed alternative pathway 3 (AP3) enzymes and transporters. We calculated fluxes of the native plant system and those of AP3 combined with the inhibition of the glycolate/glycerate transporter by using the YANAsquare package. The activity values corresponding to each enzyme in photosynthesis, photorespiration, and for synthetically designed alternative pathways were estimated. Next, we modeled the effect of the crotonyl-CoA/ethylmalonyl-CoA/hydroxybutyryl-CoA cycle (CETCH), which is a set of natural and synthetically designed enzymes that fix CO₂ manifold more than the native Calvin-Benson-Bassham (CBB) cycle. We compared estimated fluxes across various pathways in the native model and under an introduced CETCH cycle. Moreover, we combined CETCH and AP3-w/plgg1RNAi, and calculated the fluxes. We anticipate higher carbon dioxide-harvesting potential in plants with an AP3 bypass and CETCH-AP3 combination. We discuss the in vivo implementation of these strategies for the improvement of C3 plants and in natural high carbon harvesters.}, language = {en} }