Evaluation of 1-deoxy-1-[18F]fluoro-D-mannitol as a brain imaging tracer for measuring osmotic disruption following cancer therapy

1123 Objectives One of several methods for increasing brain drug delivery and bioavailability is osmotic disruption of the blood-brain barrier. Intracarotid injection of a hypertonic mannitol solution is used for improving chemotherapeutic drug administration to brain tumors. Here we report the evaluation of 1-deoxy-1-[18F]fluoro-D-mannitol in rat brain as a potential tracer for evaluating BBB permeability prior to chemotherapy administration and monitoring brain permeability changes during intracranial chemotherapy administration. Methods [18F]Mannitol was prepared from the corresponding pentaacetyl-protected tosylate in a manner similar to that for 2-FDG production. Radiofluorination was performed in acetonitrile at 120°C. After hydrolysis (0.1M HCl, 130°C), the tracer was purified by a series SepPaks: ion-retarding resin, alumina and C18 using water as the eluent. PET imaging was performed in a rat using a Siemens Focus 220 scanner with Neurologica CT scanner. [18F]Mannitol (1.2 mCi) was injected via tail-vein and imaged in list mode for one hour. Results The tracer was produced in 1.2h with yields of 10-20% (EOS) and >98% radiochemical purity. PET imaging showed very fast flow related brain accumulation and washout in the first 60 sec. Brain accumulation increased to 0.1% injected dose (%ID) at 47 second and decreased to 0.04 %ID at 5 min. Surprisingly, brain activity increased and doubled to 0.08% ID at 1 hour (SUV at 1 hour was 0.3). The images clearly indicated high brain uptake of the agent. The increased brain uptake is associated with [18F]mannitol release from blood plasma and other tissues. Conclusions High yield and no carrier added [18F]mannitol radiosynthesis was demonstrated. One hour rat imaging indicated that [18F]mannitol has adequate brain uptake. The utility of this tracer for monitoring brain chemotherapy administration should be studied further.