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

Abstract

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.

• Authors: John E Mata, Leslie A Dyal, Margorie E Slauson, James E Summerton, Christiane Loehr, Arhie Reid Tyson, Rosita Rodriguez-Proteau, Scott B Gustafson
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 3 Issue 4 Pg. 297-305 (Dec 2007) ISSN: 1549-9642 [Electronic] United States
• PMID: 17900997 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Pancreatitis-Associated Proteins
• Peptides
• REG3A protein, human
• Radiopharmaceuticals
• Technetium

Topics

• Animals
• Cell Line, Tumor
• Hydrogen-Ion Concentration
• Image Enhancement (methods)
• Lung Neoplasms (diagnostic imaging, metabolism)
• Mammary Neoplasms, Animal (diagnostic imaging, metabolism)
• Metabolic Clearance Rate
• Mice
• Pancreatitis-Associated Proteins
• Peptides (pharmacokinetics)
• Protein Binding
• Radionuclide Imaging
• Radiopharmaceuticals (pharmacokinetics)
• Technetium (pharmacokinetics)
• Tissue Distribution