Tumor imaging using technetium-99m bound to pH-sensitive peptides

摘要

Solid tumors often display metabolic abnormalities that consistently produce low pH in the extracellular space of poorly perfused tissue.These acidic regions may provide a mechanism for drug targeting.Peptides have been designed in such a manner that they exist in an anionic hydrophilic form at the pH of normal tissues,but then undergo a sharp transition to a non-ionic lipophilic form at reduced pH.Peptides were labeled with fluorescein or technicium-99m(99mTc)and evaluated in vitro and in two murine models of cancer.Our studies suggest that PAP-1,an 18 amino acid pH activated peptide with a pH of transition between hydrophilic and lipophilic forms(pT)of 6.4,will deliver fluorescein and 99mTc to tumors.Activation of PAP-1 by low pH and penetration into the plasma membrane of cells and tumors were confirmed using flow cytometry,fluorescence microscopy,and gamma scintigraphy.These results support our central hypothesis that PAP-1 may enable the selective delivery of macromolecules to tumors.This technology has potential for exploiting a common property of tumors to achieve highly specific medical intervention.