Imaging the intratumoral–peritumoral extracellular pH gradient of gliomas

摘要: Solid tumors have an acidic extracellular pH (pHe ) but near neutral intracellular (pHi ). Because pHe milieu is conducive to tumor growth and builds resistance therapy, simultaneous mapping of inside outside the (i.e., intratumoral-peritumoral gradient) fulfills important need in cancer imaging. We used Biosensor Imaging Redundant Deviation Shifts (BIRDS), which utilizes shifts non-exchangeable protons from macrocyclic chelates (e.g., 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonate) or DOTP(8-) complexed with paramagnetic thulium (Tm(3) (+) ion, generate vivo maps rat brains bearing 9L RG2 tumors. Upon TmDOTP(5-) infusion, MRI identified boundary by enhanced water transverse relaxation BIRDS allowed imaging gradients. The measured was compared pHi (31) P-MRS. In normal tissue, similar , lower than . While intratumoral for both types, peritumoral varied type. gradient much larger because found distal regions. increased presence Ki-67 positive cells beyond border suggested that more invasive tumor. These results indicate extensive correlates cell invasion. summary, has sensitivity map gradient, thereby creating preclinical applications monitoring therapeutic responses -altering drugs). Copyright © 2016 John Wiley & Sons, Ltd.