Comparative biodistribution of iodinated amino acids in rats: selection of the optimal analog for oncologic imaging outside the brain.

3-(123)I-Iodo-alpha-methyltyrosine ((123)I-3-IMT) is used for the detection of residual and recurrent brain tumors. The application of (123)I-3-IMT for the study of extracerebral malignancies is limited by its marked and rapid renal uptake. In this study, we compared the tumor uptake, biodistribution, and specificity of 5 structurally related iodinated amino acids with those of (123)I-3-IMT. The aim was to select the optimal analog for oncologic imaging outside the brain.

METHODS

We studied 3-(123)I-iodotyrosine ((123)I-3-IT), 2-(123)I-iodotyrosine ((123)I-2-IT), (123)I-iodo-azatyrosine ((123)I-IAzaT), 2-(123)I-iodophenylalanine ((123)I-2-IPhe), and 4-(123)I-iodophenylalanine ((123)I-4-IPhe). Tumor uptake and renal uptake in sarcoma-bearing rats were measured by use of in vivo dynamic imaging. The differential uptake ratio (average counts per pixel of the region of interest divided by the average counts per pixel inside the total body) and rates of tracer accumulation (K(1) values) were calculated. Results were compared with the values obtained for (123)I-3-IMT in the same rat. Tracers that demonstrated high tumor uptake were labeled with (125)I and coinjected with (18)F-FDG in rats with turpentine-induced acute inflammation. After 30 min, the rats were sacrificed and dissected. Amino acid tracer uptake in organs and tissues was measured, and the increase in uptake in the inflamed muscle was expressed relative to the increase in (18)F-FDG uptake.

RESULTS

Tumor uptake and K(1) values for (123)I-2-IT and (123)I-2-IPhe were comparable to those for (123)I-3-IMT. (123)I-4-IPhe showed high tumor uptake but a reduced K(1) value because of high blood-pool activity. (123)I-3-IT and (123)I-IAzaT did not accumulate markedly in tumor tissue. Renal accumulation of (123)I-2-IT, (123)I-2-IPhe, and (123)I-4-IPhe was at least 6 times lower than that of (123)I-3-IMT. (18)F-FDG uptake was markedly increased in areas of acute inflammation (215%). The increases for (125)I-3-IMT and (125)I-4-IPhe were 35.5% and 22.2%, respectively, of the increase for (18)F-FDG. Almost no increase was found for (125)I-2-IT (3.3%) and (125)I-2-IPhe (2.8%).

CONCLUSIONS

(123)I-2-IT and (123)I-2-IPhe are promising tracers for oncologic imaging outside the brain. (123)I-2-IT has the advantage of an established kit for radiosynthesis.