Manganese Contrast and Teslascan

Whatever happened to Teslascan?  
teslascan
To date the only manganese-based contrast agent ever approved for worldwide sales and clinical use was mangafodipir trisodium (Mn-DPDP), marketed in the 1990's under the tradename Teslascan®. Due to low sales, poor clinical performance, and concerns over toxicity, Teslascan® was withdrawn from the US market in 2003 and from the EU in 2010.

After gadolinium, the transition metal manganese (25Mn) possesses the second highest paramagnetic moment of any element. This property derives from the Mn+2 ion having 5 unpaired electrons in its 3d shell. Thus the potential of using manganese at the center of a paramagnetic contrast agent has always excited considerable interest.

After injection Teslascan® is taken up by hepatocytes and eventually excreted into the bowel. Accumulation of manganese produces a prominent T1 shortening effect, rendering normal liver bright on T1-weighted images, while non-hepatocyte-containing masses remain dark.

Mn accumulation basal ganglia
Use of Teslascan® to better delineate liver lesions. Noncontrast T1WI (left) shows 3 poorly defined liver metastases (arrows).
Post Teslascan® T1WI shows them to much better advantage. (From Schima et al under CC-BY)

Although initial clinical trials of Teslascan® demonstrated a low incidence of mild and expected adverse effects (headache, nausea, etc.), concern about the dangers of the free Mn+2 ion arose. In industrial workers Mn+2 is known to accumulate in the brain with long-term exposure producing a Parkinson-like syndrome. This risk is increased in patients with liver failure. Reports of myocardial depression also arose resulting from Mn+2 entering heart cells through Ca+2 channels.

I personally believe Mn-based contrast agents may still find a place in future pharmacopoeias, provided attention is given to developing chelating agents that attach more strongly to the metal and prevent release of the toxic free ion. Considerable research interest in animals continues, including its use in MR mapping of cytoarchitecture and neuronal projections as well as assessing cardiac viability. Even a few human studies have now reappeared in the medical literature. 

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References
     Schima W, Kulinna C, Langenberger H, Ba-Ssalamah A. Liver metastases of colorectal cancer: US, CT or MR?  Cancer Imaging 2005; Vol 5.  [DOI LINK]
     Silva AC, Lee JH, Aoki I, Koretsky AP. Manganese-enhanced magnetic resonance imaging (MEMRI): methodological and practical considerations. NMR Biomed 2004; 17:532-543.
     Singh T, Joshi S, Kershaw LE, et al. Manganese-enhanced magnetic resonance imaging of the heart. J Magn Reson Imaging 2023; 57;1011-1028.  [DOI LINK]
     Sudarshana DM, Nair G, Dwyer JT, et al. Manganese-enhanced MRI of the brain in healthy volunteers. AJNR Am J Neuroradiol 2019, 40:1309-1316.  [DOI LINK]
     Youk JH, Lee JM, Kim CS. MRI for detection of hepatocellular carcinoma: comparison of mangafodipir trisodium and gadopenetate dimeglumine contrast agents. AJR Am J Roentgenol 2004; 183:1049-1054.
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