# Labeling Peptides with Radioiodine: An Overview of Traditional and Emerging Techniques
## 7 Conclusions  
The field of radioiodinated peptide synthesis continues to evolve, driven by the need for more efficient, selective, and stable radiolabeling techniques. The choice between direct and indirect radioiodination methods depends on multiple factors, including the peptide's structure, functional groups available for labeling, and the intended application. While direct iodination remains a widely used approach due to its simplicity, indirect methods provide greater flexibility and control over labeling site specificity, thereby preserving peptide functionality and improving in vivo stability. Advancements in radioiodination chemistry have led to the development of novel prosthetic groups, click chemistry techniques, and improved purification strategies, all of which contribute to the enhanced efficiency of radiolabeling. Additionally, recent innovations in computational modeling and high-throughput screening have facilitated the optimization of reaction conditions, reducing the time and resources required for peptide radiolabeling. These technological improvements not only expand the scope of radio-pharmaceutical applications but also enhance the translational potential of radioiodinated peptides from bench to bedside. Another key frontier is the development of dual-modality imaging agents, where radioiodinated peptides are conjugated with fluorescent or MRI-active probes for complementary diagnostic insights [82; 83]. Another promising direction in radionuclide theranostics lies in the development of double-labeled peptide-based probes ensuring consistent pharmacokinetics across both diagnostic and therapeutic applications. By leveraging the strengths of dual-labeling strategies, we can achieve higher imaging resolution with PET tracers such as gallium-68 while simultaneously enabling effective targeted radionuclide therapy with isotopes like lutetium-177, actinium-225 or iodine-131 [84; 85; 86]. Despite these significant advancements, challenges remain in the field of radioiodination. One major hurdle is the potential for deiodination in vivo, which can lead to reduced imaging contrast and off-target effects [13]. Strategies to address this issue include the use of metabolically stable prosthetic groups and the incorporation of iodine isotopes into structurally protected positions within the peptide. Additionally, further research is needed to refine purification protocols to achieve high radiochemical purity while minimizing peptide degradation. Looking ahead, the continued exploration of novel chemical methodologies, coupled with advancements in radiopharmaceutical development, will pave the way for more effective and versatile radioiodinated peptides. The integration of artificial intelligence and machine learning in radiochemistry is expected to further optimize labeling strategies, enabling the rapid identification of the most suitable conditions for peptide radioiodination [87; 88]. Moreover, the development of dual-labeled peptides that combine radioiodine with other imaging or therapeutic isotopes presents an exciting avenue for multimodal diagnostics and theranostics [84]. In conclusion, radioiodinated peptides remain at the forefront of molecular imaging and targeted therapy, offering invaluable tools for the diagnosis and treatment of various diseases. The continuous refinement of radiolabeling strategies will not only improve the efficacy of these radiopharmaceuticals but also expand their clinical applicability. By addressing current challenges and leveraging cutting-edge technologies, the field of peptide radioiodination is poised for significant breakthroughs that will further advance the landscape of nuclear medicine. Conceptualization, G.F.; validation, L.C. and A.P. ; data curation, V.P. and E.S. ; writing--original draft preparation, V.P., E.S., L.C., A.P. and G.F.; writing--review and editing, V.P., E.S., L.C., A.P. and G.F.; visualization, V.P. and E.S. ; supervision, V.P.