The extracellular pH (pHe) of solid
tumors is often acidic, as a consequence of the Warburg effect, and an altered metabolic state is often associated with
malignancy. It has been shown that
acidosis can promote
tumor progression; thus, many therapeutic strategies have been adopted against
tumor metabolism; one of these involves alkalinization
therapies to raise
tumor pH to inhibit
tumor progression, improve immune surveillance, and overcome resistance to
chemotherapies. Chemical exchange saturation transfer-magnetic resonance imaging (CEST-MRI) is a noninvasive technique that can measure pH in vivo using pH-sensitive
contrast agents.
Iopamidol, an iodinated
contrast agent, clinically used for computed tomography (CT), contains
amide group
protons with pH-dependent exchange rates that can reveal the pHe of the tumor microenvironment. In this study, we optimized intraperitoneal (IP) delivery of
iopamidol to facilitate longitudinal assessments of orthotopic pancreatic
tumor pHe by CEST-MRI. Following IV-infusion and IP-bolus
injections, we compared the two protocols for assessing
tumor pH. Time-resolved CT imaging was used to evaluate the uptake of
iopamidol in the
tumor, revealing that IP-bolus delivered a high amount of
contrast agent 40 min postinjection, which was similar to the amounts reached with the IV-infusion protocol. As expected, both IP and IV injection protocols produced comparable measurements of
tumor pHe, showing no statistically significant difference between groups (p=0.16). In addition, we showed the ability to conduct longitudinal monitoring of
tumor pHe using CEST-MRI with the IP injection protocol, revealing a statistically significant increase in
tumor pHe following
bicarbonate administration (p < 0.001). In conclusion, this study shows the capability to measure pHe using an IP delivery of
iopamidol into orthotopic pancreatic
tumors, which is important to conduct longitudinal studies.