Synthesis, ^99m Tc-labeling, and preliminary biological evaluation of DTPA-melphalan conjugates

Melphalan (MFL) is a typical nitrogen mustard for the treatment of many types of cancer. For the purpose to develop novel ^99m Tc-labeled tumor imaging agents with SPECT, MFL was directly labeled by ^99m Tc using diethylene triamine pentacetate acid (DTPA) as bifunctional chelating agent. The novel ligands were successfully synthesized by conjugation of DTPA to MFL to get monosubstituted DTPA-MFL and bis-substituted DTPA-2MFL. Radiolabeling was performed in high yield to get ^99m Tc-DTPA-MFL and ^99m Tc-DTPA-2MFL, respectively, which were hydrophilic and stable at room temperature. The high initial tumor uptake with retention, good tumor/muscle ratios, and satisfactory scintigraphic images suggested the potential of ^99m Tc-DTPA-MFL and ^99m Tc-DTPA-2MFL for tumor imaging. However, the slow normal tissue clearance would be a great obstacle. Further modification on the linker and/or ^99m Tc-chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress.