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Comparative Biodistribution of Iodinated Amino Acids in Rats: Selection of the Optimal Analog for Oncologic Imaging Outside the Brain

Department of Nuclear Medicine, Academic Hospital, Free University Brussels, Jette, Belgium

3-¹²³I-Iodo--methyltyrosine (¹²³I-3-IMT) is used for the detection of residual and recurrent brain tumors. The application of ¹²³I-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 ¹²³I-3-IMT. The aim was to select the optimal analog for oncologic imaging outside the brain. Methods: We studied 3-¹²³I-iodotyrosine (¹²³I-3-IT), 2-¹²³I-iodotyrosine (¹²³I-2-IT), ¹²³I-iodo-azatyrosine (¹²³I-IAzaT), 2-¹²³I-iodophenylalanine (¹²³I-2-IPhe), and 4-¹²³I-iodophenylalanine (¹²³I-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 (K₁ values) were calculated. Results were compared with the values obtained for ¹²³I-3-IMT in the same rat. Tracers that demonstrated high tumor uptake were labeled with ¹²⁵I and coinjected with ¹⁸F-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 ¹⁸F-FDG uptake. Results: Tumor uptake and K₁ values for ¹²³I-2-IT and ¹²³I-2-IPhe were comparable to those for ¹²³I-3-IMT. ¹²³I-4-IPhe showed high tumor uptake but a reduced K₁ value because of high blood-pool activity. ¹²³I-3-IT and ¹²³I-IAzaT did not accumulate markedly in tumor tissue. Renal accumulation of ¹²³I-2-IT, ¹²³I-2-IPhe, and ¹²³I-4-IPhe was at least 6 times lower than that of ¹²³I-3-IMT. ¹⁸F-FDG uptake was markedly increased in areas of acute inflammation (215%). The increases for ¹²⁵I-3-IMT and ¹²⁵I-4-IPhe were 35.5% and 22.2%, respectively, of the increase for ¹⁸F-FDG. Almost no increase was found for ¹²⁵I-2-IT (3.3%) and ¹²⁵I-2-IPhe (2.8%). Conclusion: ¹²³I-2-IT and ¹²³I-2-IPhe are promising tracers for oncologic imaging outside the brain. ¹²³I-2-IT has the advantage of an established kit for radiosynthesis.

Key Words: amino acids • tumor imaging • inflammation • biodistribution • small-animal imaging

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