Abstract
1707
Objectives Thyronine and its iodinated analogs are transported by L type amino acid transporter (LAT) system, which has been shown to be overexpressed in many types of cancers. Our goal was to study the potential of 3′-Iodothyronine (IT) (a natural amino acid and a substrate for LAT) as a tracer for imaging tumors.
Methods [124/131I]-IT was synthesized by iodination of thyronine with [124/131I]-NaI using chloramine-T as catalyst for 2 min and purified by RP HPLC. In vitro studies were carried out in U87 brain tumor cells by incubating with [131I]-IT and percent uptake with respect to time was measured. In vivo evaluation was performed on mice with bilateral MDA-MB-468 xenografts. [124I]-IT in saline was administered intravenously to mice and imaged using small animal PET at 2, 4 and 8 h time points.
Results Radioiodination produced monoiodinated thyronine as a major product as previously reported (J Nucl Med. 1977, 18(11):1112) with isolated yield of about 40%. In vitro evaluation in U87 cell lines indicated increasing uptake with time until saturation. In vivo MicroPET imaging studies revealed uptake in tumors. ROI analysis of PET images indicated that %ID/g values in the MDA-MB-468 tumors were 0.92 ± 0.20, 0.58 ± 0.08 and 0.14 ± 0.01 at 2, 4 and 8 h respectively and the corresponding values in muscle are 0.34 ± 0.03, 0.19 ± 0.02 and 0.07 ± 0.01.
Conclusions [124/131I]-IT can be easily synthesized and purified using RP-HPLC systems. [124/131I]-IT is taken up preferentially by U87 tumor cells in vitro and MDA-MB-468 tumors in vivo. The tracer exhibits high uptake during early time points and clears from the tumor tissue with no significant retention which is characteristic of amino acid transport based tracers. The results indicate that [124/131I]-IT has potential as PET tracer for tumors overexpressing LAT.
Research Support NIH 5P50CA08643