A combined positron emission tomography (PET)- electron paramagnetic resonance imaging (EPRI) system: initial evaluation of a prototype scanner.
Tseytlin M, Stolin AV, Guggilapu P, Bobko AA, Khramtsov VV, Tseytlin O, Raylman RR.
Phys Med Biol. 2018; 63(10): 105010.
Triarylmethyl-based biradical as a superoxide probe.
Poncelet M, Driesschaert B, Bobko AA, Khramtsov VV.
Free Radic Res. 2018; 52(3): 373-379.
LPA signaling is regulated through the primary cilium: a novel target in glioblastoma.
Loskutov YV, Griffin CL, Marinak KM, Bobko AA, Margaryan NV, Geldenhuys WJ, Sarkaria JN, Pugacheva EN.
Oncogene. 2018; 37(11): 1457-1471.
Oxygen-induced leakage of spin polarization in Overhauser-enhanced magnetic resonance imaging: application for oximetry in tumors.
Gorodetskii AA, Eubank TD, Driesschaert B, Poncelet M, Ellis EJ, Khramtsov VV, Bobko AA.
J Magn Reson. 2018; 297: 42-50.
In Vivo EPR assessment of pH, pO2, redox status, and concentrations of phosphate and glutathione in the tumor microenvironment.
Bobko AA, Eubank TD, Driesschaert B, Khramtsov VV.
J Vis Exp. 2018; (133).
Exchange phenomena in the electron paramagnetic resonance spectra of the nitroxyl and trityl radicals: multifunctional spectroscopy and imaging of local chemical microenvironment.
Khramtsov VV, Bobko AA, Tseytlin MP, Driesschaert B.
Anal Chem. 2017; 89(9): 4758-4771.
Nitro-triarylmethyl radical as dual oxygen and superoxide probe.
Driesschaert B, Bobko AA, Khramtsov VV, Zweier JL.
Cell Biochem Biophys. 2017; 75(2): 241-246.
Concurrent longitudinal EPR monitoring of tissue oxygenation, acidosis, and reducing capacity in mouse xenograft tumor models.
Bobko AA, Evans J, Denko NC, Khramtsov VV.
Cell Biochem Biophys. 2017; 75(2): 247-253.
Interstitial inorganic phosphate as a tumor microenvironment marker for tumor progression.
Bobko AA, Eubank TD, Driesschaert B, Dhimitruka I, Evans J, Mohammad R, Tchekneva EE, Dikov MM, Khramtsov VV.
Sci Rep. 2017; 7: 41233.
Poly-arginine conjugated triarylmethyl radical as intracellular spin label.
Driesschaert B, Bobko AA, Eubank TD, Samouilov A, Khramtsov VV, Zweier JL.
Bioorg Med Chem Lett. 2016; 26(7): 1742-1744.
Redox properties of the nitronyl nitroxide antioxidants studied via their reactions with nitroxyl and ferrocyanide.
Bobko AA, Khramtsov VV.
Free Radic Res. 2015; 49(8): 919-926.
The importance of the tumor microenvironment (TME) in tumor progression, invasion, and therapy is widely recognized. Intermittent and hypoxic oxygenation (pO2) and extracellular acidosis (pHe) of tumor tissues are among the most established hallmarks in solid TME, while extracellular inorganic phosphate (Pi) has been recently identified as a new signaling molecule of importance in tumorigenesis (marker of metastatic potential).
The αvβ3 and αvβ5 integrins are usually expressed at low levels in most adult epithelia but can be highly upregulated in some tumors. These integrins are involved in angiogenesis and metastasis of solid tumors, and their inhibition resulted in significant reduction of functional vessel density, retardation of tumor growth, and metastasis in vivo.
In this project we propose to develop theranostic multifunctional paramagnetic trityl probes for in vivo monitoring of basic physiological parameters (pO2, pH, Pi) using electron paramagnetic resonance-based techniques and patient-derived tumor xenograft (PDX) models.
Proposed trityl probes are designed to have minimal toxicity, a wide range of pharmacokinetic time, and antiangiogenic therapeutic effects due to high affinity of the probes to the αvβ3 integrins in tumor tissue.
The best probe formulations are used to construct a real-time TME profile during tumor development and antiangiogenic treatment using theranostic
We hypothesize that the TME signature can predict levels of success for αvβ integrins based on antiangiogenic therapy. Successful completion of this proposed project will result in development of new theranostic paramagnetic multifunctional probes which can be easily modified with appropriate targeting motif to study drug therapeutic effects.