CORE D The Radiochemistry Core will carry out four Specific Aims: (1) Provide oxygen-15 radiopharmaceuticals for PET measurement of CBF, CBV, OEF and CMRO2 (2) Optimize and automate the synthesis of [11C] mannitol for PET studies of brain mannitol uptake (3)Implement, optimize and automate the synthesis of [11 C] methyl alpha aminoisobutyric acid for PET studies of blood:brain barrier permeability (4)Construct a steady state oxygen-15gas inhalation system to permit PET studies of CBV, OEF and CMRO2 in subjects who are not endotracheally intubated or who cannot actively inhale. Oxygen-15 will be produced via the 14N(d,n) 150 reaction. [150]H20, [150] CO, and [150] 02 will be produced by a system that has been in operation for 20 years. We have synthesized [11C]-D-mannitol by a simple reduction of [C11]-D-mannose with sodium borohydride. During the period of this grant we will optimize the synthesis and automate this system to reduce operator exposure. The synthesis of [11 C] methyl alpha aminoisobutyric acid will be modeled after a published procedure of Nagren et al. We have at hand the authentic material to be used as standard for our HPLC purification (Aldrich # 86,022-0) and have also prepared the substrate for the radiosynthesis, a protected AIB methyl ester. During the first two years this grant will implement, optimize and automate this synthesis. We will then supply [11C]-MeAIB for patient studies during years 3-5. The brief inhalation method for measuring CBV, OEF and CMRO2 employs a rapid injection of [150]H20 and two brief inhalations of [150] CO, and [150] 02. A problem occurs in subjects who are unable to voluntarily inhale a sufficiently deep breath of [150]-gas to achieve adequate radioactivity delivery the brain for good counting statistics from the 40-sec PET scan. In contrast, the steady-state method employs continuous passive inhalation of [150] gases. We now request funds to construct the steady state oxygen-15 gas inhalation system in the NNICU PET facility to allow us to effectively measure CBV, OEF and CMRO2 in a larger fraction of the clinically eligible patients.
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