title: Biodistribution and pharmacokinetics of I-131 labelled 4-iodophenylacetic acid.
abstract: Phenylacetate has been reported to have a potent anti-proliferative and anti-differentiating effect in haematological malignancies and in solid tumours at non-toxic concentrations. This study is a preliminary investigation of 131I-radiolabelled 4-iodophenylacetic acid as a potential radiopharmaceutical equivalent. Radiolabelling by isotope exchange gave a radiochemical yield of 53 ± 6 %, and a radiochemical purity of 97.8 ± 1.2 %, as qualified by HPLC. The labelled product was used in Sprague Dawley rats and athymic nude (balb/c) mice xenografted with WHCO1 cells (an oesophageal cancer cell line). Dynamic and static scans were carried out on rats with a SPECT camera to determine the biodistribution of 4-[131I]-iodophenylacetic acid. No target organ was found after 5 h with fast excretion from all organs via the kidney into the urine. Ex vivo studies (termination 5 h after injection) were performed in 12 xenograft mice carrying tumours of 5-8 mm on their right flank. Tumour uptake of 4 + 0.4 % ID/g was recorded with a tumour to background ratio of 2. As the blood pool still contains high levels of activity after 5 h in mice, increased tumour uptake may occur at later time points, which might warrant further investigation.
authors.affiliation: Drug Research and Development, North West University, South Africa. zeevaart@necsa.co.za
authors.forename: Jan Rijn
authors.initials: JR
authors.lastname: Zeevaart
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szucs
authors.forename: Tamsyn
authors.initials: T
authors.lastname: Pulker
authors.forename: Thato
authors.initials: T
authors.lastname: Sello
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bracher
authors.forename: Mike
authors.initials: M
authors.lastname: Sathekge
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D006207:Half-Life; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010648:Phenylacetates / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous
chemical_list: C579622:4-iodophenylacetic acid; D000964:Antimetabolites, Antineoplastic; D007457:Iodine Radioisotopes; D010648:Phenylacetates; D019275:Radiopharmaceuticals; C025136:phenylacetic acid