Three carboxylic acid drugs, valproic acid(VPA), n-butyric acid(BA), and 4-phenylbutyric acid(PBA) have been used or investigated for the treatment of various human diseases including epilepsy and cancer.  They have also been reported to affect epigenetic processes through histone deacetylase (HDAC) inhibition.  In order to determine the pharmacokinetics and biodistribution of each drug and/or its labeled metabolites, we labeled each with C-11 using [11C]CO2 and the appropriate Grignard reagent.  Dynamic PET studies for 90 min were performed in three female baboons. [11C]BA was metabolized rapidly with only 20% remaining in plasma by 5 minutes post iv injection.  Brain uptake was low (VPA>PBA) and C-11 was excreted through kidney.  Interestingly, while [11C]BA showed moderate uptake in spleen and pancreas, [11C]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. These unique biodistribution patterns may shed light on the therapeutic and side effect profile of these drugs.

Synthesis and positron emission tomography studies of three C-11 labeled carboxylic
acid drugs, [11C]butyric acid, [11C]valporic acid, [11C]4-phenylbutyric acid

240th National Meeting (2010)

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Synthesis and positron emission tomography studies of three C-11 labeled carboxylic acid drugs, [11C]butyric acid, [11C]valporic acid, [11C]4-phenylbutyric acid

Synthesis and positron emission tomography studies of three C-11 labeled carboxylic acid drugs, [¹¹C]butyric acid, [¹¹C]valporic acid, [¹¹C]4-phenylbutyric acid