Abstract
PurposeMetabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH.MethodsIn this study we combined APT MRI and 31P‐MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty‐two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi).ResultsWhile APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo.ConclusionsAs differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.
Highlights
KRIKKEN ET AL.Metabolism in cancer is widely investigated by the use of magnetic resonance imaging (MRI)
Assessment of hormone receptor status was performed on the pretreatment core biopsy; six patients had human epidermal growth factor receptor 2 (HER2) positive tumors and 16 patients had HER2 negative tumors
From the amide proton transfer (APT)‐MRI, the mean APT signal was determined inside the tumor volume (Figure 1C) based on the three‐pool Lorentzian fit
Summary
The contrast depends on the exchange rate of saturated mobile protons to the bulk water resonance. This enables indirect imaging of endogenous molecules containing these mobile protons, such as amides (proteins and peptides), a process which is called amide proton transfer (APT). In theory,[21] the measured amide signal is primarily related to the concentration of mobile amide protons, the exchange rate (dependent on pH), duration of saturation pulse, and T1 relaxation of water. In another study,[32] reduced APT signal during NAC treatment was observed These findings are counterintuitive, if one interprets the data solely in terms of the pH dependence of the chemical exchange rate of amide protons, which is base‐catalyzed. APT‐MRI and 31P‐MRSI were acquired in breast cancer patients receiving NAC treatment before and after the first cycle of NAC using 7 T MRI
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