RESUMEN
The cross sections of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were measured at the ARRONAX facility by using the 70 MeV cyclotron, with particular attention to the production of the theranostic radionuclide 67Cu. Enriched 68Zn material was electroplated on silver backing and exposed to alow-intensity proton beam by using the stacked-foils target method. Since 67Cu and 67Ga radionuclides have similar half-lives and same γ-lines (they both decay to 67Zn), a radiochemical process aimed at Cu/Ga separation was mandatory to avoid interferences in γ-spectrometry measurements. A simple chemical procedure having a high separation efficiency (>99%)was developed and monitored during each foil processing, thanks to the tracer isotopes 61Cu and 66Ga.Nuclear cross sections were measured in the energy range 35-70 MeV by using reference reactions recommended by the International Atomic Energy Agency (IAEA) to monitor beam flux. In comparison with literature data a general good agreement on the trend of the nuclear reactions was noted, especially with latest measurements, but slightly lower values were obtained in case of 67Cu. Experimental results of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were also compared with the theoretical values estimated by using the nuclear reaction code TALYS. The production yield of the theranostic radionuclide 67Cu was estimated considering the results obtained in this work.
Las secciones eficaces de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga se midieron en la instalación ARRONAX utilizando el ciclotrón 70 MeV, con especial atención a la producción del radionucleidos teranóstico 67Cu. El material enriquecido 68Zn se galvanizó sobre soporte de plata y se expuso a un haz de protones de baja intensidad utilizando un blanco de láminas apiladas. Como los radionucleidos 67Cu y 67Ga tienen periodos de semidesintegración y líneas γ similares (ambos se desintegran a 67Zn), un proceso radioquímico dirigido a la separación Cu / Ga fue obligatorio para evitar interferencias en las mediciones de espectrometría γ. Se desarrolló un procedimiento químico simple con una alta eficiencia de separación (> 99%) durante cada procesamiento de la lámina, gracias a los isótopos trazadores 61Cu y 66Ga. Las secciones eficaces nucleares se midieron en el rango de energía de 35-70 MeV utilizando reacciones de referencia recomendadas por el Organismo Internacional de Energía Atómica (OIEA) para monitorear el flujo del haz. Al comparar con los datos de la literatura, se observó una buena concordancia en general con la tendencia de las reacciones nucleares, particularmente con las últimas mediciones, pero se obtuvieron valores ligeramente inferiores en el caso de 67Cu. Los resultados experimentales de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga también se compararon con los valores teóricos estimados usando el código de reacción nuclear TALYS. El rendimiento de producción del radionucleido teranóstico 67Cu se estimó considerando los resultados obtenidos en este trabajo.
RESUMEN
Abstract The cross sections of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were measured at the ARRONAX facility by using the 70 MeV cyclotron, with particular attention to the production of the theranostic radionuclide 67Cu. Enriched 68Zn material was electroplated on silver backing and exposed to alow-intensity proton beam by using the stacked-foils target method. Since 67Cu and 67Ga radionuclides have similar half-lives and same γ-lines (they both decay to 67Zn), a radiochemical process aimed at Cu/Ga separation was mandatory to avoid interferences in γ-spectrometry measurements. A simple chemical procedure having a high separation efficiency (>99%)was developed and monitored during each foil processing, thanks to the tracer isotopes 61Cu and 66Ga.Nuclear cross sections were measured in the energy range 35-70 MeV by using reference reactions recommended by the International Atomic Energy Agency (IAEA) to monitor beam flux. In comparison with literature data a general good agreement on the trend of the nuclear reactions was noted, especially with latest measurements, but slightly lower values were obtained in case of 67Cu. Experimental results of the 68Zn(p,2p)67Cu,68Zn(p,2n)67Ga and 68Zn(p,3n)66Ga reactions were also compared with the theoretical values estimated by using the nuclear reaction code TALYS. The production yield of the theranostic radionuclide 67Cu was estimated considering the results obtained in this work.
Resumen Las secciones eficaces de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga se midieron en la instalación ARRONAX utilizando el ciclotrón 70 MeV, con especial atención a la producción del radionucleidos teranóstico 67Cu. El material enriquecido 68Zn se galvanizó sobre soporte de plata y se expuso a un haz de protones de baja intensidad utilizando un blanco de láminas apiladas. Como los radionucleidos 67Cu y 67Ga tienen periodos de semidesintegración y líneas γ similares (ambos se desintegran a 67Zn), un proceso radioquímico dirigido a la separación Cu / Ga fue obligatorio para evitar interferencias en las mediciones de espectrometría γ. Se desarrolló un procedimiento químico simple con una alta eficiencia de separación (> 99%) durante cada procesamiento de la lámina, gracias a los isótopos trazadores 61Cu y 66Ga. Las secciones eficaces nucleares se midieron en el rango de energía de 35-70 MeV utilizando reacciones de referencia recomendadas por el Organismo Internacional de Energía Atómica (OIEA) para monitorear el flujo del haz. Al comparar con los datos de la literatura, se observó una buena concordancia en general con la tendencia de las reacciones nucleares, particularmente con las últimas mediciones, pero se obtuvieron valores ligeramente inferiores en el caso de 67Cu. Los resultados experimentales de las reacciones 68Zn (p, 2p) 67Cu, 68Zn (p, 2n) 67Ga y 68Zn (p, 3n) 66Ga también se compararon con los valores teóricos estimados usando el código de reacción nuclear TALYS. El rendimiento de producción del radionucleido teranóstico 67Cu se estimó considerando los resultados obtenidos en este trabajo.
RESUMEN
Despite the advances associated with the introduction of PET technology, reasons to consider that SPECT, particularly with 99mTc radiopharmaceuticals will continue playing an important role in Nuclear Medicine, are presented. The details examined are the following ones. An improvement of the technology SPECT is appreciated with the development of new detection systems and the advantages of the appearance of the hybrid systems SPECT / TAC. The biggest half-life of the main SPECT radionuclides like 123 pipe and 99mTc in comparison with PET radionuclides, facilitates its transportation at larger distances, allow the realization of studies with radiopharmaceuticals with different radionuclides in the same patient, and the possibility of the detection of lesions of low tracer accumulation. Finally the main base core for 99mTc complex formation with different ligands are reviewed, as a background that assure the appearance of new radiopharmaceuticals of practical interest. The oncological and cardiological potential applications are examined with emphasis in these last ones. It is clear that 99mTc radiopharmacy will continue playing an important role in nuclear medicine.
En el trabajo se exponen razones para considerar que el SPECT, particularmente con radiofármacos de 99mTc continuará teniendo un importante papel en medicina nuclear, no obstante los avances asociados a la incorporación de la tecnología PET. Las razones que se examinan son las siguientes. Se aprecia un mejoramiento de la tecnología SPECT con el desarrollo de nuevos sistemas de detección y las ventajas de la aparición de los sistemas híbridos SPECT/TAC, la mayor vida media de los principales radionúclidos SPECT como 123 pipe y 99mTc en comparación con los radionúclidos PET, lo que posibilita su traslado a mayores distancias, la realización de estudios con radiofármacos con más de un radionúclido en el mismo paciente y la posibilidad de detectar lesiones de baja captación, favorecido por lo indicado de las vidas medias. Finalmente se examinan los principales núcleos base de formación de complejos de 99mTc con distintos ligandos que aseguran la aparición de nuevos radiofármacos de interés. Se examinan las potenciales aplicaciones oncológicas y cardiológicas con énfasis en estas últimas. Se considera que la radiofarmacia del 99mTc continuará jugando un importante papel en medicina nuclear.
RESUMEN
A novel class of Tc-99m complexes able to cross the blood brain barrier has been investigated and described here. These compounds are formed by reacting the bis-substituted nitrido precusors [99mTc(N)(PS)2] (PS = phosphino-thiol ligand) with triethylborane (BEt3) under strictly anhydrous conditions and using non-aqueous solvents. The molecular structure of these tracers was not fully established, but preliminary experimental evidence suggests that they result from the interaction of the Lewis base [99mTc(N)(PS)2] with the Lewis acid BEt3, which leads to the formation of the novel -B-Nº Tc- adduct. After purification and recovery in a physiological solution, the new borane-nitrido Tc-99m derivatives were injected in rats for evaluating their in vivo biological behavior. Results showed a significant accumulation in brain tissue, thus indicating that these complexes are capable of penetrating the intact blood brain barrier. Uptake in the central nervous system was confirmed by imaging the distribution of activity on the integrated living animal using a YAP(S)SPECT small animal scanner.
Uma nova classe de complexos de Tc-99m capazes de atravessar a barreira hemato-encefálica foi investigada e descrita neste trabalho. Estes compostos são formados reagindo os precursores bissubstituídos do nitrido [99mTc(N)(PS)2] (PS = phosphino-tiol ligante) com trietillborano (BEt3) sob restritas condições anidras e usando solventes não aquosos. A estrutura molecular desses traçadores não foi totalmente estabelecida, mas evidências experimentais preliminares sugerem que eles resultam da interação da base de Lewis [99mTc(N)(PS)2] com o ácido de Lewis BEt3, levando a formação do novo aducto -B-Nº Tc-. Após purificação e recuperação em uma solução fisiológica, os novos derivados borano-nitrido-Tc-99m foram injetados em ratos para avaliação de seu comportamento biológico in vivo. Os resultados mostraram uma acumulação significativa no tecido cerebral, indicando que estes complexos são capazes de atravessar a barreira hemato-encefálica íntegra. A captação pelo sistema nervosa central foi confirmada pela imagem da distribuição de atividade em animais vivos, usando um scanner para animais pequenos (YAP(S)SPECT).
Asunto(s)
Cerebro , Óxido NítricoRESUMEN
The chemical methods for the production of technetium-99m radiopharmaceuticals containing a terminal TcºN triple bond have been established more than a decade ago. From that time, the chemistry of nitrido Tc-99m complexes has provided a highly efficient tool for the design and preparation of novel classes of diagnostic agents, and a number of potentially useful radiopharmaceuticals have been discovered. In particular, nitrido technetium-99m tracers have been developed for heart perfusion imaging. In this short review, the chemical and biological properties of the neutral myocardial perfusion tracer bis(N-ethoxy, N-ethyl-dithiocarbamato) nitrido Tc-99m (TcN-NOEt) will be summarized along with the preparation and preliminary biological evaluation of the first class of monocationic nitrido technetium-99m radiopharmaceuticals exhibiting improved biodistribution properties closer to those expected for an ideal perfusion imaging agent