Radioiodinated 6-iodo-D-meta-tyrosine : Characterization of Uptake in DLD-1 Colon Cancer Cells and Biodistribution in Mice

Introduction: 123I-6-iodo-D-meta-tyrosine (123I-6-D-mTyr) is an iodine-labeled D-amino acid employed potentially in molecular imaging of tumors. We used its 125I-labeled analogue (6-I-D-mTyr), which has a long half-life and is suitable for basic studies, to examine the mechanism of 123I-6-D-mTyr accumulation in DLD-1 human colon cancer cells and its biodistribution in normal mice. Methods: DLD-1 cells (5.0×105) suspended in 5 ml of culture medium (Dulbecco`s Modified Eagles Medium) containing fetal bovine serum and L-glutamine were seeded into 6-cmφ culture dishes and cultured at 37°C, CO2 5%, and pH 7.4. Time curves for the uptake of 6-I-D-mTyr (18.5 kBq) into DLD-1 cells were constructed, and the transport systems were analyzed by uptakeinhibition experiments using 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a system L–specific inhibitor) and 2-(methylamino)isobutyric acid (a system A–specific inhibitor) at an uptake temperature of 4°C. Also, 6-I-D-mTyr (11.1 kBq) was administered to male ddY mice (6 weeks old) by injection into the tail vein, and the time-course of its biodistribution was determined. Results: The uptake of 6-I-D-mTyr into DLD-1 cells peaked at 10 min. Membrane transport inhibition studies indicated that ca. 70% of the incorporated amount was due to membrane transport (ca. 50% was due to transport system L, and the other ca. 20% was due to membrane transport via an unknown mechanism), whereas inhibition unsaturated uptake was estimated to be ca. 30% (4°C). Physiologic accumulation of 6-I-D-mTyr in normal mouse tissues was low overall, and clearance from the blood was observed to be rapid. Accumulation in the stomach was also low, indicating excellent metabolic resistance to de-iodination enzymes. Conclusions: In normal mice, the concentration of 6-I-D-mTyr in organs and tissues decreased rapidly following administration, whereas in DLD-1 mice, both the uptake and retention of 6-I-D-mTyr were excellent. These results highlight the potential of 6-I-D-mTyr as a new labeling agent for use in molecular imaging of tumors.