<p>Compounds labelled with ¹¹C (<i>β</i>⁺, t_1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized reconstruction methods to produce time-resolved images of the radioactivity distribution in living subjects. </p><p>The feasibility of preparing [¹¹C]methyl iodide from [¹¹C]methane and iodine via a single pass through a non-thermal plasma reactor was explored. [¹¹C]Methyl iodide with a specific radioactivity of 412 ± 32 GBq/µmol was obtained in 13 ± 3% decay-corrected radiochemical yield within 6 min via catalytic hydrogenation of [¹¹C]carbon dioxide (24 GBq) and subsequent iodination, induced by electron impact. </p><p>Labelled ethyl-, propyl- and butyl iodide was synthesized, within 15 min, via palladium-mediated carbonylation using [¹¹C]carbon monoxide. The carbonylation products, labelled carboxylic acids, esters and aldehydes, were reduced to their corresponding alcohols and converted to alkyl iodides. [1-¹¹C]Ethyl iodide was obtained via palladium-mediated carbonylation of methyl iodide with a decay-corrected radiochemical yield of 55 ± 5%. [1-¹¹C]Propyl iodide and [1-¹¹C]butyl iodide were synthesized via the hydroformylation of ethene and propene with decay-corrected radiochemical yields of 58 ± 4% and 34 ± 2%, respectively. [1-¹¹C]Ethyl iodide was obtained with a specific radioactivity of 84 GBq/mmol from 10 GBq of [¹¹C]carbon monoxide. [1-¹¹C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-¹¹C]butyl iodide with 146 GBq/mmol from 8 GBq. </p><p>Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-¹¹C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with amine to yield <i>N-</i>[<i>carbonyl</i>-¹¹C]benzylacrylamide. In an alternative method, [<i>carbonyl</i>-¹¹C]acrylamides were synthesized in decay-corrected radiochemical yields up to 81% via palladium-mediated carbonylative cross-coupling of vinyl halides and amines. Starting from 10 ± 0.5 GBq of [¹¹C]carbon monoxide, <i>N-</i>[<i>carbonyl</i>-¹¹C]benzylacrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq/µmol. </p>

Compounds labelled with 11C (β+, t1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized reconstruction methods to produce time-resolved images of the radioactivity distribution in living subjects. The feasibility of preparing [11C]methyl iodide from [11C]methane and iodine via a single pass through a non-thermal plasma reactor was explored. [11C]Methyl iodide with a specific radioactivity of 412 ± 32 GBq/µmol was obtained in 13 ± 3% decay-corrected radiochemical yield within 6 min via catalytic hydrogenation of [11C]carbon dioxide (24 GBq) and subsequent iodination, induced by electron impact. Labelled ethyl-, propyl- and butyl iodide was synthesized, within 15 min, via palladium-mediated carbonylation using [11C]carbon monoxide. The carbonylation products, labelled carboxylic acids, esters and aldehydes, were reduced to their corresponding alcohols and converted to alkyl iodides. [1-11C]Ethyl iodide was obtained via palladium-mediated carbonylation of methyl iodide with a decay-corrected radiochemical yield of 55 ± 5%. [1-11C]Propyl iodide and [1-11C]butyl iodide were synthesized via the hydroformylation of ethene and propene with decay-corrected radiochemical yields of 58 ± 4% and 34 ± 2%, respectively. [1-11C]Ethyl iodide was obtained with a specific radioactivity of 84 GBq/mmol from 10 GBq of [11C]carbon monoxide. [1-11C]Propyl iodide was synthesized with a specific radioactivity of 270 GBq/mmol from 12 GBq and [1-11C]butyl iodide with 146 GBq/mmol from 8 GBq. Palladium-mediated hydroxycarbonylation of acetylene was used in the synthesis of [1-11C]acrylic acid. The labelled carboxylic acid was converted to its acid chloride and subsequently treated with amine to yield N-[carbonyl-11C]benzylacrylamide. In an alternative method, [carbonyl-11C]acrylamides were synthesized in decay-corrected radiochemical yields up to 81% via palladium-mediated carbonylative cross-coupling of vinyl halides and amines. Starting from 10 ± 0.5 GBq of [11C]carbon monoxide, N-[carbonyl-11C]benzylacrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq/µmol.

<p>The positron emitting radionuclide ⁶⁸Ga (T_1/2 = 68 min) might become of practical interest for clinical positron emission tomography (PET). The metallic cation, ⁶⁸Ga(III), is suitable for complexation with chelators, either naked or conjugated with biological macromolecules. Such labelling procedures require pure and concentrated preparations of ⁶⁸Ga(III), which cannot be sufficiently fulfilled by the presently available ⁶⁸Ge/⁶⁸Ga generator eluate. This thesis presents methods to increase the concentration and purity of ⁶⁸Ga obtained from a commercial ⁶⁸Ge/⁶⁸Ga generator. The use of the preconcentrated and purified ⁶⁸Ga eluate along with microwave heating allowed quantitative ⁶⁸Ga-labelling of peptide conjugates within 15 min. The specific radioactivity of the radiolabelled peptides was improved considerably compared to previously applied techniques using non-treated generator eluate and conventional heating. A commercial ⁶⁸Ge/⁶⁸Ga generator in combination with the method for preconcentration/purification and microwave heated labelling might result in an automated device for ⁶⁸Ga-based radiopharmaceutical kit production with quantitative incorporation of ⁶⁸Ga(III).</p><p>Macromolecules were labelled with ⁶⁸Ga(III) either directly or via a chelator. The bifunctional chelator, DOTA, was conjugated in solution to peptides, an antibody and oligonucleotides. The peptides had varied pI values, constitution, and length ranging from 8 to 53 amino acid residues. The oligonucleotides were of various sequences and length with modifications in backbone, sugar moiety and both 3' and 5' ends with a molecular weight up to 9.8 kDa. The bioconjugates were labeled with ⁶⁸Ga(III), and the resulting tracers were characterised chemically and biologically. The identity of the ⁶⁸Ga-labelled bioconjugates was verified. The tracers were found to be stable and their biological activity maintained. Specific radioactivity was shown to be an important parameter influencing the feasibility of accurate imaging data quantification.</p><p>Furthermore, ⁶⁸Ga-labelled peptide imaging was shown to be a useful tool to study peptide adsorption to microstructures in a chemical analysis device.</p>

The positron emitting radionuclide 68Ga (T1/2 = 68 min) might become of practical interest for clinical positron emission tomography (PET). The metallic cation, 68Ga(III), is suitable for complexation with chelators, either naked or conjugated with biological macromolecules. Such labelling procedures require pure and concentrated preparations of 68Ga(III), which cannot be sufficiently fulfilled by the presently available 68Ge/68Ga generator eluate. This thesis presents methods to increase the concentration and purity of 68Ga obtained from a commercial 68Ge/68Ga generator. The use of the preconcentrated and purified 68Ga eluate along with microwave heating allowed quantitative 68Ga-labelling of peptide conjugates within 15 min. The specific radioactivity of the radiolabelled peptides was improved considerably compared to previously applied techniques using non-treated generator eluate and conventional heating. A commercial 68Ge/68Ga generator in combination with the method for preconcentration/purification and microwave heated labelling might result in an automated device for 68Ga-based radiopharmaceutical kit production with quantitative incorporation of 68Ga(III). Macromolecules were labelled with 68Ga(III) either directly or via a chelator. The bifunctional chelator, DOTA, was conjugated in solution to peptides, an antibody and oligonucleotides. The peptides had varied pI values, constitution, and length ranging from 8 to 53 amino acid residues. The oligonucleotides were of various sequences and length with modifications in backbone, sugar moiety and both 3' and 5' ends with a molecular weight up to 9.8 kDa. The bioconjugates were labeled with 68Ga(III), and the resulting tracers were characterised chemically and biologically. The identity of the 68Ga-labelled bioconjugates was verified. The tracers were found to be stable and their biological activity maintained. Specific radioactivity was shown to be an important parameter influencing the feasibility of accurate imaging data quantification. Furthermore, 68Ga-labelled peptide imaging was shown to be a useful tool to study peptide adsorption to microstructures in a chemical analysis device.

S'ha desenvolupat una nova estratègia per la síntesi ràpida i eficient de L-[metil-11C]metionina basada en el captive solvent method. La reacció de L-homocisteína (dissolució bàsica en aigua/etanol 1:1) amb [11C]CH3I en un loop de HPLC va permetre la formació del radiotraçador desitjat amb elevat rendiment radioquímic (38.4 ± 4.1%) en un temps curt (< 12 min). Tots el paràmetres analítics compleixen les especificacions requerides per la versió actual de la Farmacopea Espanyola, tot i que els valors d'activitat específica obtinguts van ser relativament baixos. Degut a això, es van estudiar i quantificar les principals fonts que contribueixen a la contaminació de carboni-12 durant les síntesis de [11C]CH3I efectuades segons el "wet" method. Es va observar que la principal font de contaminació de CO2 no radioactiu (contribució>90%) és el propi procés de bombardeig, probablement degut a la combustió (causada per les altes temperatures i pressions assolides durant la irradiació) dels compostos que contenen carboni i que es troben al gas irradiat (o a l'interior del blanc). Es van establir procediments generals per realitzar abans, durant i després de la radiosíntesi per prevenir la contaminació exterior i, d'aquesta manera, augmentar l'activitat específica dels radiotraçadors sintetitzats.En quant al marcatge amb nitrogen-13, s'ha desenvolupat un procés totalment automàtic per a la producció de [13N]NO2- a partir de [13N]NO3- generat en el ciclotró. El precursor radioactiu [13N]NO2- s'ha utilitzat per la radiosíntesi de compostos amb interès biològic com ara S-nitrosotiols (donadors de NO.), N-nitrosamines (molècules amb potencials efectes carcinogènics) i azo compostos (amb possible aplicació com a radiotraçadors per a la detecció in vivo de plaques de &#946;-amiloide). En tots els casos es van obtenir excel·lents conversions radioquímiques (48.7% - 74.5% per S-[13N]nitrosotiols, 45.6% - 53.4% per N-[13N]nitrosamines i 40.0% - 58.3% per 13N-azo compostos) i bons rendiments radioquímics (33.8% - 60.6% per S-[13N]nitrosotiols, 34.0% - 37.8% per N-[13N]nitrosamines i 20.4% - 47.2% per 13N-azo compostos). A més a més, s'ha dissenyat i implementat un mòdul automàtic amb control remot pel marcatge de molècules amb 13N. / Se ha desarrollado una nueva estrategia para la síntesis rápida y eficiente de L-[metil-11C]metionina basada en el captive solvent method. La reacción de L-homocisteína (disolución básica en agua/etanol 1:1) con [11C]CH3I en un loop de HPLC permitió la formación del radiotrazador deseado con elevado rendimiento radioquímico (38.4 ± 4.1%) en un tiempo corto (< 12 min). Todos los parámetros analíticos cumplían las especificaciones requeridas por la versión actual de la Farmacopea Española, aunque los valores de actividad específica obtenidos fueron relativamente bajos. Por ello, se estudiaron y cuantificaron las principales fuentes que contribuyen a la contaminación de carbono-12 durante las síntesis de [11C]CH3I efectuadas según el "wet" method. Se observó que la principal fuente de contaminación de CO2 no radiactivo (contribución>90%) es el propio proceso de bombardeo, probablemente debido a la combustión (causada por las altas temperaturas y presiones alcanzadas durante la irradiación) de los compuestos que contienen carbono y que se encuentran presentes en el gas irradiado (o en el mismo cuerpo del blanco). Se establecieron procedimientos generales para realizar antes, durante y con posterioridad a la radiosíntesis para prevenir la contaminación exterior y, de esta manera, aumentar la actividad específica de los radiotrazadores sintetizados.Respecto al marcaje con nitrógeno-13, se ha desarrollado un proceso totalmente automático para la producción de [13N]NO2- a partir del [13N]NO3- generado en el ciclotrón. El precursor radiactivo [13N]NO2- se ha utilizado para la radiosíntesis de compuestos con interés biológico tales como S-nitrosotioles (donadores de NO.), N-nitrosaminas (moléculas con potenciales efectos carcinogénicos) y azo compuestos (con posible aplicación como radiotrazadores para la detección in vivo de placas de &#946;-amiloide). En todos los casos se obtuvieron excelentes conversiones radioquímicas (48.7% - 74.5% para S-[13N]nitrosotioles, 45.6% - 53.4% para N-[13N]nitrosaminas y 40.0% - 58.3% para 13N-azo compuestos) y buenos rendimientos radioquímicos (33.8% - 60.6% para S-[13N]nitrosotioles, 34.0% - 37.8% para N-[13N]nitrosaminas y 20.4% - 47.2% para 13N-azo compuestos). Además, se ha diseñado e implementado un módulo automático con control remoto para el marcaje de moléculas con 13N. / A new strategy for the fast and efficient synthesis of L-[methyl-11C]methionine based on the captive solvent method has been developed. The in loop reaction of a basic water/ethanol 1:1 solution of L-homocysteine with [11C]CH3I led to the formation of the desired radiotracer with high radiochemical yield (38.4 ± 4.1%) in short production time (< 12 min). All analytical parameters were within the specifications of the current version of the Spanish Pharmacopoeia, although specific radioactivity values were relatively low. Thus, the main sources of carbon-12 during the synthesis of [11C]CH3I by the "wet" method were studied and the contribution attributable to each individual source was quantified. The most relevant contamination of non-radioactive CO2 (contribution>90%) was shown to be generated during the bombardment process, probably due to the combustion (caused by high temperature and pressure during irradiation) of carbon carrier compounds present in the irradiated gas (or target body). General procedures to be performed before, during and after the radiosynthesis were established to prevent external contamination and to improve the specific radioactivity of 11C-labeled radiotracers synthesized from [11C]CH3I produced via the "wet" method. Concerning 13N-labeling, a fully automatic process for the production of [13N]NO2- from cyclotron generated [13N]NO3- has been developed. The radioactive precursor [13N]NO2- has been used for the synthesis of biologically interesting 13N-labeled compounds such as S-nitrosothiols (well-known NO. donors), N-nitrosamines (molecules with potent carcinogenic effects) and azo compounds (with putative application as imaging probes for in vivo detection of &#946;-amyloid plaques). In all cases, excellent radiochemical conversion (48.7% - 74.5% for S-[13N]nitrosothiols, 45.6% - 53.4% for N-[13N]nitrosamines and 40.0% - 58.3% for 13N-labeled azo compounds) and good radiochemical yields (33.8% - 60.6% for S-[13N]nitrosothiols, 34.0% - 37.8% for N-[13N]nitrosamines and 20.4% - 47.2% for 13N-labeled azo compounds) were achieved. An automatic remote controlled synthesis module for the preparation of 13N-labeled structures has been designed and implemented.