Gd-PCTA-Ach

Gd-PCTA-Ach is a macrocyclic gadolinium-based MRI contrast agent characterized by high kinetic inertness and moderate albumin affinity. Its ability to bind with albumin effectively prolongs its circulation time in the bloodstream. Gd-PCTA-Ach is primarily excreted through the kidneys, with approximately 10% of the dose eliminated via the hepatobiliary route, demonstrating a unique dual-excretion profile. This compound enables high-quality imaging of brain and liver tumors and holds significant diagnostic value in research concerning liver cancer and gliomas.

Gd-PCTA-Ach (0.5-400 mM; 24 h, 37 °C, 5% CO2) exhibits negligible cytotoxicity, maintaining cell viability above 80% in HEK-293, AML-12, and C8-D1A cells after treatment at concentrations ranging from 0.5 to 400 mM for 24 hours.

Gd-PCTA-Ach (0.1 mmol [Gd]/kg; intravenous injection; single bolus administration) produces prolonged and strong contrast enhancement in multiple mouse organs, as confirmed by imaging and biodistribution analysis, with primary excretion through the kidneys (approximately 90%) and partial excretion via hepatobiliary pathways (about 10%). It enables clear imaging of orthotopic hepatocellular carcinoma in mice, with statistically significant increases in liver-tumor contrast-to-noise ratio (CNR) observed at 3 and 30 minutes post-injection. The hepatic uptake of Gd-PCTA-Ach is partly mediated by OATP transporters, as pre-administration of the OATP inhibitor bromosulfophthalein significantly reduces liver enhancement and increases renal enhancement. Effective brain tumor imaging is achieved in mice at doses of 0.05-0.1 mmol [Gd]/kg, with superior performance at 0.1 mmol [Gd]/kg, and comparable enhancement at a lower dose of 0.05 mmol [Gd]/kg to standard contrast agents.