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Tumor imaging using technetium-99m bound to pH-sensitive peptides.
|Title||Tumor imaging using technetium-99m bound to pH-sensitive peptides.|
|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Mata JE, Dyal LA, Slauson ME, Summerton JE, Loehr C, Tyson AR, Rodriguez-Proteau R, Gustafson SB|
|Journal||Nanomedicine : nanotechnology, biology, and medicine|
|Date Published||2007 Dec|
|Keywords||Animals, Cell Line, Tumor, Hydrogen-Ion Concentration, Image Enhancement, Lung Neoplasms, Mammary Neoplasms, Animal, Metabolic Clearance Rate, Mice, Peptides, Protein Binding, Radiopharmaceuticals, Technetium, Tissue Distribution|
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 technetium-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.