Biodistribution and Pharmacokinetics of I-131 Labelled 4- Iodophenylacetic Acid

Jan      Rijn Zeevaart; Zoltan      Szucs; Tamsyn      Pulker; Thato      Sello; Jacqueline      Bracher; Mike      Sathekge

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.

Keywords: SPECT, phenylacetic acid metabolism, solid tumour, 131I.

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