Rapid and simplified synthesis of [18F]MISO and its use in subarachnoidal hemorrhage PET imaging

Abstract

Resumen del póster presentado al "Annual Congress of the European Association of Nuclear Medicine" celebrado en Gothenburg (Suecia) del 18 al 22 de octubre de 2014.-- et al.[Aim]: Difered cerebral damage secondary to the vasospasm due to subarachnoidal hemorrhage is an important cause of morbi‐mortality. We propose the use of the PET tracer 1‐[18F]Fluoro‐3‐(2‐nitro‐imidazol‐1‐yl)‐propan‐2‐ol ([18F]MISO) to visualize the hypoxia caused by vasospasm. On the other hand [18F]MISO synthesis process can be optimized, avoiding HPLC purification, with solid phase extraction cartridges (SPE). [Matherial and methods]: [18F]MISO was obtained by nucleophilic substitution of 1‐(2´‐Nitro‐1´‐imidazolyl)‐2‐O‐tetrahydropyranyl‐3‐O‐toluenesulfonyl‐propanediol (NITTP) precursor with 18F‐, following Tang et al. method. We adapted our TracerLab FXFN module reducing some synthesis steps. 18F‐ was obtained from a 18/9 MeV Cyclone Cyclotron. Azeotropic distillation was reduced to 5 minutes. Fluorination of precursor took 5 minutes. Hydrolysis with HCl 1M of the protective groups and later neutralization with 1N NaOH was about 6 minutes. The solution was purified passing through three Sep‐Paks cartridges; Alumina‐SCX‐C18 connected in series. Final product was eluted in hydro‐alcoholic mixture (90/10). The completed synthesis was carried out in 21 minutes. Radiochemical purity of [18F]MISO (higher than 95%) was determined by analytical HPLC, and pH tested before injection to the animals. Two Wistar rats were used to obtain [18F]MISO PET images. 100‐200uL of blood obtained from the tail vein were injected in the Cisterna magna to cause the hemorrhage at one animal. The control animal was injected with saline, with the same procedure. Two days after the hemorrhage [18F]MISO PET/CT studies were carried out at a Mosaic MicroPET (Philips) and Bioscan nanoCT scanner to study the hemorrhage‐induced hypoxia. 100MBq of [18F]MISO were injected to each animal at the dorsal tail vein. After three hours of incorporation, PET images were adquired. CT scan followed the PET study. Images of both studies could be overlaid, because the animals remained anesthetized and immobilized during all process. [Results]: and discussion The synthesis steps were optimized; azeotropic distillation was completed in 5 minutes and we avoided HPLC purification using the SPE instead. Total synthesis time was reduced to 21 minutes with high radiochemical yield, up to 45% without decay correction. [18F]MISO PET Images will be available at poster.Peer Reviewe