[18F]Fluoride radiolabelling and stability of B-F…P pincer triphenylphosphonium derivatives for applications in mitochondrial imaging.

2636 Objectives Mitochondrial membrane potential (MMP) dependent uptake of triphenylphosphonium (TPP) derivatives is an important marker for detection of cellular dysfunction in cancer and cardiac hypertrophy. Lipophilicity is a key property for uptake into the mitochondria. It has been suggested that less lipophilic (-3 to -1) compounds are more suitable for cancer imaging and the more lipophilic (0 to 2) appropriate for imaging of cardiac dysfunction. The objective of this work is [18F]fluoride radiolabelling of a range of pincer TPP derivatives, forming a B-F bond which links to the phosphorus, with different overall charges and lipophilicity, and to determine the stability of the 18F-TPP labelled compounds. Methods Different concentrations of cold TPP derivatives and varying reaction times were used to identify the optimum reaction conditions. Serum stability was determined in human serum at 370C for 3 hours. Phosphate buffer stability was determined at room temperature for 3 hours. Specific activity (SA) was quantified for each 18F- TPP derivative by HPLC. The value of log p was determined from the partition between octanol and phosphate buffer. Results A range of TPP derivatives were radiolabelled with 18F using an isotopic exchange reaction and also under carrier-added conditions converting the boronic ester to BF3. The radiochemical yield was determined for each 18F labelled compound showing high radiochemical yield (RCY) between 70% - 90% and high radiochemical stability between 80% - 95% for a range of 18F labelled compounds. SA and log P value of 18F labelled TPP derivatives were determined. Conclusions A novel set of B-F…P pincer 18F-TPP derivatives were radiolabelled and shown to have high stability. SA and log P values of each 18F labelled derivative indicates that they are suitable for in vitro studies in either cancer or heart cells and in vivo studies in animal models.