Radiometal-Based PET/MRI Contrast Agents for Sensing Tumor Extracellular pH

• Published in: Biosensors (Basel) Vol. 12; no. 2; p. 134
• Main Authors: Pollard, Alyssa C, de la Cerda, Jorge, Schuler, F William, Pollard, Tyler R, Kotrotsou, Aikaterini, Pisaneschi, Federica, Pagel, Mark D
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20.02.2022; MDPI
• Subjects: Acidosis; Biomarkers; Cancer; Cell division; Chromatography; Contrast agents; Contrast media; copper-64; Evaluation; gallium-68; In vivo methods and tests; Magnetic resonance imaging; Mass spectrometry; Medical research; Metabolism; Pancreatic cancer; PET/MRI; pH effects; Positron emission; Radioactivity; Scientific imaging; Sensors; Solvents; Tomography; Tumors; United States > US; pH; gallium-68; cancer; PET/MRI; contrast agents; copper-64
• ISSN: 2079-6374; 2079-6374
• DOI: 10.3390/bios12020134

Acidosis is a useful biomarker for tumor diagnoses and for evaluating early response to anti-cancer treatments. Despite these useful applications, there are few methods for non-invasively measuring tumor extracellular pH, and none are routinely used in clinics. Responsive MRI contrast agents have been developed, and they undergo a change in MRI signal with pH. However, these signal changes are concentration-dependent, and it is difficult to accurately measure the concentration of an MRI contrast agent in vivo. PET/MRI provides a unique opportunity to overcome this concentration dependence issue by using the PET component to report on the concentration of the pH-responsive MRI agent. Herein, we synthesized PET/MRI co-agents based on the design of a pH-dependent MRI agent, and we have correlated pH with the r relaxivity of the MRI co-agent. We have also developed a procedure that uses PET radioactivity measurements and MRI R relaxation rate measurements to determine the r relaxivity of the MRI co-agent, which can then be used to estimate pH. This simultaneous PET/MRI procedure accurately measured pH in solution, with a precision that depended on the concentration of the MRI co-agent. We used our procedure to measure extracellular pH in a subcutaneous flank model of MIA PaCa-2 pancreatic cancer. Although the PET co-agents were stable in serum, post-imaging studies showed evidence that the PET co-agents were degraded in vivo. These results showed that tumor acidosis can be evaluated with simultaneous PET/MRI, although improvements are needed to more precisely measure MRI R relaxation rates, and ensure the in vivo stability of the agents.