Positron emission tomography has increased the demand for new carbon-11 radiolabeled tracers and building blocks. A promising radiolabeling synthon is [(11) C]benzyl iodide ([(11) C]BnI), because the benzyl group is a widely present functionality in biologically active compounds. Unfortunately, synthesis of [(11) C]BnI has received little attention, resulting in limited application. Therefore, we investigated the synthesis in order to significantly improve, automate, and apply it for labeling of the dopamine D2 antagonist [(11) C]clebopride as a proof of concept. [(11) C]BnI was synthesized from [(11) C]CO2 via a Grignard reaction and purified prior the reaction with desbenzyl clebopride. According to a one-pot procedure, [(11) C]BnI was synthesized in 11 min from [(11) C]CO2 with high yield, purity, and specific activity, 52 ± 3% (end of the cyclotron bombardment), 95 ± 3%, and 123 ± 17 GBq/µmol (end of the synthesis), respectively. Changes in the [(11) C]BnI synthesis are reduced amounts of reagents, a lower temperature in the Grignard reaction, and the introduction of a solid-phase intermediate purification. [(11) C]Clebopride was synthesized within 28 min from [(11) C]CO2 in an isolated decay-corrected yield of 11 ± 3% (end of the cyclotron bombardment) with a purity of >98% and specific activity (SA) of 54 ± 4 GBq/µmol (n = 3) at the end of the synthesis. Conversion of [(11) C]BnI to product was 82 ± 11%. The reliable synthesis of [(11) C]BnI allows the broad application of this synthon in positron emission tomography radiopharmaceutical development.

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Hydroxy-aryl-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles represent interesting chemical scaffolds, but synthetic access to these compounds is limited. The reaction of 2-aroyl-cyclohexanones with 2-cyanoacetamide and base in ethanol has been reported to lead to the formation of the tetrahydroisoquinoline isomer. We show that depending on the electronic nature of the para-substituent on the aryl ring, formation of the regioisomeric tetrahydroquinoline isomer can significantly compete. The electron-donating or -withdrawing properties of the para-substituent of the aryl ring determines the ratio of product isomers. A series of 2-aroyl-cyclohexanones, with para-substituents ranging from electron-donating to electron-withdrawing, were reacted with [2-(13)C]-cyanoacetamide. The product ratio and absolute regiochemistry were directly determined by quantitative (13)C, HMBC, and NOESY NMR spectroscopy on the reaction mixtures. A clear relationship between the regioisomeric product ratio and the Hammett sigma values of the substituents is demonstrated. This is explained by the separate in situ yields, which reveal that the pathway leading to the tetrahydroquinoline regioisomer is significantly more sensitive toward the electronic nature of the para-substituent than the pathway leading to the tetrahydroisoquinoline. Semiempirical AM1 molecular orbital calculations on the starting electrophile 2-aroyl-cyclohexanone support a correlation between the energy of the LUMOs and the regioisomeric product ratio. Our results facilitate synthetic access to a range of these interesting synthetic intermediates.

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Table of contentsOP03 Selective extraction of medically-related radionuclides from proton-irradiated thorium targetsV. Radchenko, J.W. Engle, C. Roy, J. Griswold, M.F. Nortier, E.R. Birnbaum, M. Brugh, S. Mirzadeh, K. D. John, M.E. FassbenderOP04 Comparison of [68Ga]FSC(succ-RGD)3 and [68Ga]NODAGA-RGD for PET imaging of αvβ3 integrin expressionChuangyan Zhai, Gerben M. Franssen, Milos Petrik, Peter Laverman, Clemens DecristoforoOP05 A new NPY-Y1R targeting peptide for breast cancer PET imagingAit-Mohand Samia, Dumulon-Perreault Véronique, Guérin BrigitteOP06 The influence of multivalency on CCK 2 receptor targetingD. Summer, A. Kroess, C. Rangger, H. Haas, P. Laverman, F. Gerben, E. von Guggenberg, C.DecristoforoOP07 SPECT Imaging of αvβ3 Expression by [99mTc(N)PNP43]- Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5Cristina Bolzati, Nicola Salvarese, Fiorenzo Refosco, Laura Meléndez-Alafort, Debora Carpanese, Antonio Rosato, Michele Saviano, Annarita Del Gatto, Daniela Comegna, Laura ZaccaroOP09 New dienophiles for the inverse-electron-demand Diels-Alder reaction and for pretargeted PET imagingEmilie Billaud, Muneer Ahamed, Frederik Cleeren, Elnaz Shahbazali, Tim Noël, Volker Hessel, Alfons Verbruggen and Guy BormansOP10 New complexing agent for Al18F-labelling of heat-sensitive biomolecules: Synthesis and preclinical evaluation of Al18F-RESCA1-HASCleeren F, Lecina J, Koole M, Verbruggen A and Bormans GOP11 A novel versatile precursor efficient for F-18 radiolabelling via click-chemistryB. Lugatoa, S. Stucchia, E.A. Turollaa, L. Giulianoa, S.Toddea, P. FerraboschibOP12 A general applicable method to quantify unidentified UV impurities in radiopharmaceuticalsR.P. Klok, M.P.J. Mooijer, N.H. Hendrikse, A.D. WindhorstOP13 Development of [18F]Fluoro-C-glycosides to radiolabel peptidesCollet C., Petry N., Chrétien F., Karcher G., Pellegrini-Moïse N., Lamandé-Langle S.OP14 A Microfluidic Approach for the 68Ga-labeling of PSMAHBED-CC and NODAGA-RGDSarah Pfaff, Cecile Philippe, Markus Mitterhauser, Marcus Hacker, Wolfgang WadsakOP16 Surprising reactivity of astatine in the nucleophilic substitution of aryliodonium salts: application to the radiolabeling of antibodiesFrançois Guérard, Yong-Sok Lee, Sébastien Gouard, Kwamena Baidoo, Cyrille Alliot, Michel Chérel, Martin W. Brechbiel, Jean-François GestinOP17 64Cu-NOTA-pertuzumab F(ab')2 fragments, a second-generation probe for PET imaging of the response of HER2-positive breast cancer to trastuzumab (Herceptin)Lam K, Chan C, Reilly RMOP18 Development of radiohalogenated analogues of a avb6-specific peptide for high LET particle emitter targeted radionuclide therapy of cancerSalomé Paillas, John Marshall, Jean-Pierre Pouget, Jane SosabowskiOP19 Ligand Specific Efficiency (LSE) as a guide in tracer optimizationEmmanuelle Briard, Yves P. Auberson, John Reilly, Mark Healy, David SykesOP23 The radiosynthesis of an 18F-labeled triglyceride, developed to visualize and quantify brown adipose tissue activityAndreas Paulus, Wouter van Marken Lichtenbelt,Felix Mottaghy,...