Synthesis and In Vitro/In Vivo Stability Evaluation of Various Radioiodinated Tyrosine Derivatives

Radioiodinated drugs face limited application due to severe in vivo deiodination. In this study, nine tyrosine derivatives were synthesized and evaluated to develop stable radioiodinated prosthetic groups to reduce deiodination. Biodistribution results revealed that replacing phenolic hydroxyl and amino groups with methoxy and acetamide groups enhanced stability. Compound 131I-8 exhibited the highest stability, with a maximum thyroid uptake of 1.13 ± 0.12 %ID (approximately one-20th of 131I-Tyr). It’s high stability was explained by in vitro stability experiments and molecular docking. A new PSMA-targeted radioiodinated drug, [125/131I]IMPA, was synthesized to verify whether compound 8 remained stable after conjugation with drugs. It exhibited a lower thyroid uptake of only 0.19 ± 0.03 %ID, approximately 100-fold lower than that of the control compound [131I]ITPA, which has a tyrosine moiety as the radioiodination site. In conclusion, 8 is a small, easily labeled, and highly stable prosthetic group with promising potential for developing stable radioiodinated drugs and broadening their therapeutic application.