The goals of this study were to compare the efficacy of the new manganese-based magnetic resonance imaging (MRI) contrast agent Mn-PyC3A to the commercial gadolinium-based agents Gd-DOTA and to Gd-EOB-DTPA to detect tumors in murine models of breast cancer and metastatic liver disease, respectively, and to quantify the fractional excretion and elimination of Mn-PyC3A in rats.
T1-weighted contrast-enhanced MRI with 0.1 mmol/kg Mn-PyC3A was compared with 0.1 mmol/kg Gd-DOTA in a breast cancer mouse model (n = 8) and to 0.025 mmol/kg Gd-EOB-DTPA in a liver metastasis mouse model (n = 6). The fractional excretion, 1-day biodistribution, and 7-day biodistribution in rats after injection of 2.0 mmol/kg [52Mn]Mn-PyC3A or Gd-DOTA were quantified by 52Mn gamma counting or Gd elemental analysis. Imaging data were compared with a paired t test; biodistribution data were compared with an unpaired t test.
The postinjection-preinjection increases in tumor-to-muscle contrast-to-noise ratio (ΔCNR) 3 minutes after injection of Mn-PyC3A and Gd-DOTA (mean ± standard deviation) were 17 ± 3.8 and 20 ± 4.4, respectively (P = 0.34). Liver-to-tumor ΔCNR values at 8 minutes postinjection of Mn-PyC3A and Gd-EOB-DTPA were 28 ± 9.0 and 48 ± 23, respectively (P = 0.11). Mn-PyC3A is eliminated with 85% into the urine and 15% into the feces after administration to rats. The percentage of the injected doses (%ID) of Mn and Gd recovered in tissues after 1 day were 0.32 ± 0.12 and 0.57 ± 0.12, respectively (P = 0.0030), and after 7 days were 0.058 ± 0.051 and 0.19 ± 0.052, respectively (P < 0.0001).
Mn-PyC3A provides comparable tumor contrast enhancement to Gd-DOTA in a mouse breast cancer model and is more completely eliminated than Gd-DOTA; partial hepatobiliary elimination of Mn-PyC3A enables conspicuous delayed phase visualization of liver metastases.
From the *Division of Surgical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston
†Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown
‡Institute for Innovation in Imaging, Massachusetts General Hospital, Boston, MA.
Received for publication April 16, 2019; and accepted for publication, after revision, May 22, 2019.
Conflicts of interest and sources of funding: This work was supported by grants from the National Institutes of Health (K25HL128899, R21EB022804, R44DK113906, P41RR014075, R01EB009062, and S10OD010650) and the Department of Energy (DESC0015773). P.C. and E.M.G. hold equity and consult to Reveal Pharmaceuticals, a company that is working to develop a manganese-based MRI contrast agent.
The other authors report no conflicts of interest.
Correspondence to: Eric M. Gale, PhD, Athinoula A. Martinos Center for Biomedical Imaging, 149 Thirteenth St, Suite 2301, Charlestown, MA 02129. E-mail: email@example.com.
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