Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): pH calibration for poly-L-lysine and a starburst dendrimer

The ability to measure proton exchange rates in tissue using MRI would be very useful for quantitative assessment of magnetization transfer properties, both in conventional MT imaging and in the more recent chemical exchange saturation transfer (CEST) approach. CEST is a new MR contrast mechanism that depends on several factors, including the exchange rate of labile protons in the agent in a pH-dependent manner. Two new methods to monitor local exchange rate based on CEST are introduced. The two MRI-compatible approaches to measure exchange are quantifying exchange using saturation time (QUEST) dependence and quantifying exchange using saturation power (QUESP) dependence. These techniques were applied to poly-L-lysine (PLL) and a generation-5 polyamidoamine dendrimer (SPD-5) to measure the pH dependence of amide proton exchange rates in the physiologic range. Data were fit both to an analytical expression and to numerical solutions to the Bloch equations. Results were validated by comparison with exchange rates determined by two established spectroscopic methods. The exchange rates determined using the four methods were pooled for the pH-calibration curve of the agents consisting of contributions from spontaneous (k_o) acid catalyzed (K_a), and base catalyzed (k _b) exchange rate constants. These constants were k_o = 68.9 Hz, k_a = 1.21 Hz, k_b = 1.92 x 10⁹ Hz, and k_o = 106.4 Hz, k_a = 25.8 Hz, k_b = 5.45 × 10⁸ Hz for PLL and SPD-5, respectively, showing the expected predominance of base-catalyzed exchange for these amide protons.