A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH

Abstract

Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. These previous studies have used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of both agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH-CEST ratio correlation for each agent. These results showed that both agents had similar performance characteristics, although iopromide produced a pH measurement with a higher dynamic range while iopamidol produced a more precise pH measurement. We then compared the performance of both agents to measure in vivo extracellular pH (pHe) within xenograft tumor models of Raji lymphoma and MCF-7 breast cancer. Our results showed that the pHe values measured with each agent were not significantly different. Also, iopromide consistently measured a greater region of the tumor relative to iopamidol in both tumor models. Therefore, an iodinated contrast agent for acidoCEST MRI should be selected based on the measurement properties needed for a specific biomedical study and the pharmacokinetic properties of a specific tumor model.

A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals

“…Our studies in this report used a saturation time of 6 seconds, a saturation power of 3 µT, and a Lorentzian line shape fitting method that can detect CEST signal amplitudes of 4.4%. These conditions are similar to our previously reported in vivo CEST MRI studies with diaCEST agents that used a satuation time of 3.8 to 5 seconds, 2.8 µT saturation power, and Lorentzian line shape fitting analyses to detect CEST signal amplitudes of approximately 2% (13,19–21). Therefore, translation of our agent to in vivo studies appears feasible.…”

Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI

“…White Gaussian noise was added to each pre-injection and post-injection CEST spectrum at a signal-to-noise ratio (SNR) of 40 and then the post-injection spectrum was subtracted from the pre-injection spectrum. An SNR of 40 and a concentration of 20 mM were chosen because the simulated difference CEST spectrum was similar to in vivo CEST spectra from our past studies [14]. Bloch fitting was performed on the simulated difference CEST spectrum to estimate the pH value.…”

Clinical applications of chemical exchange saturation transfer (CEST) MRI

“…The chemical exchange rate of an amide proton is base‐catalyzed, and the CEST signal amplitude of each aryl amide has a different dependency on pH, so that the ratio of these two CEST signals from a CT agent can be used to measure pH . Iopromide (Ultravist) has shown the best precision for measuring pH, although iopamidol (Isovue) is generally preferred due to its superior detection sensitivity . A ratio of the CEST signals from a single agent is inherently independent of concentration, and a CEST signal ratio has also been shown to be independent of the endogenous T 1 relaxation time and B 1 inhomogeneity, and largely independent of fluctuations in the physiological temperature range, which improves the accuracy of pH measurements …”