Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2014 May 20;111(20):7254-9. doi: 10.1073/pnas.1405240111. Epub 2014 May 1.

Understanding the pharmacological properties of a metabolic PET tracer in prostate cancer.

Author information

1
Program in Molecular Pharmacology and Chemistry, andDepartments of Radiology.
2
Medical Physics.
3
Departments of Radiology.
4
Neurology, and.
5
Department of Physics, University of Rhode Island, Kingston, RI 02881; and.
6
Program in Molecular Pharmacology and Chemistry, andDepartments of Radiology,Neurology, and.
7
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 donald.engelman@yale.edu lewisj2@mskcc.org.
8
Program in Molecular Pharmacology and Chemistry, andDepartments of Radiology,Medical Physics,Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
9
Program in Molecular Pharmacology and Chemistry, andDepartments of Radiology, donald.engelman@yale.edu lewisj2@mskcc.org.

Abstract

Generally, solid tumors (>400 mm(3)) are inherently acidic, with more aggressive growth producing greater acidity. If the acidity could be targeted as a biomarker, it would provide a means to gauge the pace of tumor growth and degree of invasiveness, as well as providing a basis for predicting responses to pH-dependent chemotherapies. We have developed a (64)Cu pH (low) insertion peptide (pHLIP) for targeting, imaging, and quantifying acidic tumors by PET, and our findings reveal utility in assessing prostate tumors. The new pHLIP version limits indiscriminate healthy tissue binding, and we demonstrate its targeting of extracellular acidification in three different prostate cancer models, each with different vascularization and acid-extruding protein carbonic anhydrase IX (CAIX) expression. We then describe the tumor distribution of this radiotracer ex vivo, in association with blood perfusion and known biomarkers of acidity, such as hypoxia, lactate dehydrogenase A, and CAIX. We find that the probe reveals metabolic variations between and within tumors, and discriminates between necrotic and living tumor areas.

PMID:
24785505
PMCID:
PMC4034234
DOI:
10.1073/pnas.1405240111
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center