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

Authors

Nerissa Therese Viola-Villegas
Sean D. Carlin
Ellen Ackerstaff
Kuntal K. Sevak
Vadim Divilov
Inna Serganova
Natalia Kruchevsky
Michael Anderson
Ronald G. Blasberg
Oleg A. Andreev, University of Rhode IslandFollow
Donald M. Engelman
Jason A. Koutcher
Yana K. Reshetnyak, University of Rhode IslandFollow
Jason S. Lewis

Document Type

Article

Date of Original Version

2014

Abstract

Generally, solid tumors (>400 mm³) 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 ⁶⁴Cu 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.

Citation/Publisher Attribution

Viola-Villegas, N., Carlin, S. D., Ackerstaff, E., Sevak, K. K., Dilov, V., Serganova, I., Kruchevsky, N.,...Lewis, J. S. (2014). Understanding the pharmacological properties of a metabolic PET tracer in prostate cancer. Proc. Acad. Natl. Sci., 111(20), 7254-7259. doi: 10.1073/pnas.1405240111

Available at: https://doi.org/10.1073/pnas.1405240111