Synthesis, radiosynthesis, and in vitro characterization of [ 125I]-2- iodo-L-phenylalanine in a R1M rhabdomyosarcoma cell model as a new potential tumor tracer for SPECT

Abstract

[ 125I]-2-iodo-L-phenylalanine, a new radioiodinated phenylalanine analog was evaluated as a potential specific tumor tracer for SPECT. The tracer is obtained with an overall radiochemical yield of at least 98%, a purity of >99%, and a specific activity of 11 MBq/mmol in one pot Kit conditions using the Cu 1+ assisted isotopic exchange. The tracer is evaluated in vitro using R1M rat rabdomyosarcoma cells in HEPES buffer with and without Na + ions and in MEM buffer. The uptake of [ 125I]-2-iodo-L-phenylalanine follows a reversible pseudo-first-order reaction which is the same in presence and absence of Na + ions, but the compound is not incorporated into the cell proteins. The reversible uptake is proven to occur with the same affinity as L-henylalanine by a saturable transport system which is competitively inhibited by BCH, an L transport type selective molecule. Trans-stimulation of the efflux by BCH and typical L transported amino acids shows that the transporter is of the antiport type and fulfils all the properties of the LAT1 heterodimer transport system. [ 125I]-2-iodo-L-phenylalanine is thus a phenylalanine analog that for the uptake uses for the major part the LAT1 transport system which is known to be over-expressed in tumor cells. This, together with the easy Kit preparation, makes [ 123I]-2-iodo-L-phenylalanine a promising tumor specific tracer for SPECT.