title: 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 Cu1+ 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.
authors.affiliation: Nuclear Medicine Department/BEFY, Vrije Universiteit Brussel, Belgium. jjmerten@vub.ac.be
authors.forename: J
authors.initials: J
authors.lastname: Mertens
authors.forename: V
authors.initials: V
authors.lastname: Kersemans
authors.forename: M
authors.initials: M
authors.lastname: Bauwens
authors.forename: C
authors.initials: C
authors.lastname: Joos
authors.forename: T
authors.initials: T
authors.lastname: Lahoutte
authors.forename: A
authors.initials: A
authors.lastname: Bossuyt
authors.forename: G
authors.initials: G
authors.lastname: Slegers
mesh_terms: D000465:Algorithms; D000818:Animals; D002021:Buffers; D045744:Cell Line, Tumor; D006207:Half-Life; D007202:Indicators and Reagents; D009363:Neoplasm Proteins / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011786:Quality Control; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging*; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C496694:2-iodophenylalanine; D002021:Buffers; D007202:Indicators and Reagents; D009363:Neoplasm Proteins; D019275:Radiopharmaceuticals; D010649:Phenylalanine