Synthesis, 99mTc‐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 ^99mTc‐labeled tumor imaging agents with SPECT, MFL was directly labeled by ^99mTc 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 ^99mTc‐DTPA‐MFL and ^99mTc‐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 ^99mTc‐DTPA‐MFL and ^99mTc‐DTPA‐2MFL for tumor imaging. However, the slow normal tissue clearance would be a great obstacle. Further modification on the linker and/or ^99mTc‐chelate to improve the tumor targeting efficacy and in vivo kinetic profiles is currently in progress.