A novel technology for the imaging of acidic prostate tumors by positron emission tomography.
Solid tumors often develop an acidic environment due to the Warburg effect. The effectiveness of diagnosis and therapy may therefore be enhanced by the design and use of pH-sensitive agents that target acidic tumors. Recently, a novel technology was introduced to target acidic tumors using pH low insertion peptide (pHLIP), a peptide that inserts across cell membranes as an alpha-helix when the extracellular pH (pH(e)) is acidic. In this study, we expanded the application of the pHLIP technology to include positron emission tomography imaging of the acidic environment in prostate tumors using (64)Cu conjugated to the pHLIP ((64)Cu-DOTA-pHLIP). Studies showed that this construct avidly accumulated in LNCaP and PC-3 tumors, with higher uptake and retention in the LNCaP tumors. Uptake correlated with differences in the bulk pH(e) of PC-3 and LNCaP tumors measured in magnetic resonance spectroscopy experiments by the (31)P chemical shift of the pH(e) marker 3-aminopropylphosphonate. This article introduces a novel class of noninvasive pH-selective positron emission tomography imaging agents and opens new research directions in the diagnosis of acidic solid tumors.
Division of Radiological Sciences, Department of Radiology, Washington University School of Medicine, St Louis, MO, USA.
Amy L
AL
Vāvere
Gráinne B
GB
Biddlecombe
William M
WM
Spees
Joel R
JR
Garbow
Dayanjali
D
Wijesinghe
Oleg A
OA
Andreev
Donald M
DM
Engelman
Yana K
YK
Reshetnyak
Jason S
JS
Lewis
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003301:Copper Radioisotopes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008301:Maleimides; D008565:Membrane Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D008969:Molecular Sequence Data; D049268:Positron-Emission Tomography / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging*
D003301:Copper Radioisotopes; D008301:Maleimides; D008565:Membrane Proteins; C533201:pHLIP protein