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Introduction:

Magnetic resonance imaging (MRI) is routinely used to diagnosis hepatic neoplasms. However, Gadolinium (Gd) is contraindicated in patients with severe renal impairment, and recent evidence also suggests Gd accumulates in brain tissue after repeated contrast injections. Manganese (Mn2+) is a paramagnetic ion that is cleared via biliary excretion, and provides an ideal alternative to Gd-based MR contrast agents. We present a novel Mn-based contrast agent, [Mn(PyC3A)(H2O)]- (referred to as PyC3A), and compare its efficacy to gadoxetic acid (Eovist) by imaging orthotopically implanted colorectal cancer hepatic metastases in mice.

Methods:

Male BALB/c mice (n = 8) were injected in the left lobe of the liver with 5x104 MC26/MCA-26 murine colon carcinoma cells, and were imaged on postoperative day 10 using a 4.7T MR scanner with PyC3A and gadoxetic acid (Eovist) 24 hrs apart. Signal contrast-to-noise ratio (CNR) was calculated for normal liver relative to tumor for each probe and compared.

Results:

Relaxivity of PyC3A in blood plasma was shown to be comparable to commercial Gd contrast agents. Biodistribution analysis confirmed that PyC3A clears via a mixed renal/hepatobiliary pathway with greater than 99% clearance within 24 hours. For imaging hepatic metastases, all mice survived to the study endpoint and developed radiographically discernible tumors (5 ± 2 mm diameter) without evidence of carcinomatosis. Calculated CNRs for liver relative to tumor for all recorded times are shown in Table 1. There was no difference in CNR between gadoxetic acid and PyC3A for all time points, suggesting near-equivalent enhancement of normal liver and tumor by both probes.

Conclusions:

PyC3A provides resolution of metastatic liver metastases that is comparable to gadoxetic acid. PyC3A may provide a safe and effective alternative to Gd constrast agents for imaging hepatic neoplasms in patients with renal impairment.

Table 1. Contrast-to-Noise Ratio (CNR) of Normal Liver Relative to Tumor

Time (minutes post injection) Gadoxetic Acid PyC3A p-value 
2.61 ± 1.08 2.60 ± 1.64 0.92 
7.72 ± 4.67 7.53 ± 3.02 0.93 
7.85 ± 3.89 8.85 ± 4.43 0.66 
13 8.02 ± 3.98 7.62 ± 5.49 0.88 
18 9.79 ± 4.17 5.60 ± 3.08 0.06 
23 8.72 ± 4.16 7.03 ± 2.06 0.36 
Time (minutes post injection) Gadoxetic Acid PyC3A p-value 
2.61 ± 1.08 2.60 ± 1.64 0.92 
7.72 ± 4.67 7.53 ± 3.02 0.93 
7.85 ± 3.89 8.85 ± 4.43 0.66 
13 8.02 ± 3.98 7.62 ± 5.49 0.88 
18 9.79 ± 4.17 5.60 ± 3.08 0.06 
23 8.72 ± 4.16 7.03 ± 2.06 0.36 

Citation Format: Derek J. Erstad, Ian Ramsay, Mozhdeh Sojoodi, Christian Farrar, NIcholas J. Rotile, Shen Li, Sarani Ghoshal, Lanuti Michael, Peter Caravan, Kenneth K. Tanabe, Bryan C. Fuchs, Eric Gale. A novel manganese MRI contrast agent (PyC3A) for the evaluation of hepatic neoplasms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 659.

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