The library of new smart contrast agents based on Gd3+, Eu3+, and Tb3+ used as biomarkers is in continuous development due to its applications in diagnostic imaging. The search for safer and more efficient contrast agents has focused on the design of compounds that exhibit high relaxivity. Herein, we present alternative synthetic strategies for the development of theoretically high-relaxivity synthons based on lanthanides using the Solomon–Bloembergen–Morgan equations through click chemistry and direct addition. Special attention has been devoted to the analysis of the different aspects interfering with the successful acquisition of these complexes and their troubleshooting during their synthesis. Our preliminary results showed that not only the mathematical background needs to be considered, but also the synthetic strategy and the use of procedures free of metallic ions favor the total synthesis of these challenging complexes.