Blomlie, Viggo

Jynge, Per

Sivanandan, R.

English

SIHF Vitenarkiv

LETTERSManganese Uptake and Accumulation in the Human BrainSudarshana et al1 are to be commended for their meticulousstudy of potential brain MR imaging in humans with use ofmangafodipir (Mn dipyridoxyl diphosphate [MnDPDP]) as acontrast agent. MnDPDP is a multifunctional chelate releasingcalcium-stalking paramagnetic Mn ions for MR imaging anda catalytic antioxidant for therapy.2 In healthy volunteers,MnDPDP raised the signal intensity (SI) in the exocrine glandsin the head and neck, chorioid plexus, and anterior pituitarygland but not beyond the BBB. The observations are importantbecause the infusion time (,10minutes) and dose (5 mmol/kg)have been standard in MR imaging of the liver and pancreas.Thus, the study confirms that a brief infusion of 1 diagnosticdose does not cause MR imaging contrast enhancement in thebrains of humans with an intact BBB and normal liverfunction.Concerning future brain Mn uptake studies, we find it rele-vant to address a patient who received MnDPDP in a total doseof 140mmol/kg during 8months.3 In this patient with terminalcancer of the colon, MnDPDP (10mmol/kg) was administered forthe protection of normal tissue during 14 cycles of chemotherapywith anticancer agents (oxaliplatin and 5-fluorouracil). The regi-men was well-tolerated without the adverse effects of chemother-apy, and there was a notable relief of pain. At end of treatment,mild Parkinson-like symptoms occurred, and brain MR imaging(Fig 1), images not previously disclosed, showed high SI in thebasal ganglia (caudate nucleus, globus pallidus, putamen, andthalamus). However, the SI was also high in the corpus callosum,mesencephalon, brain stem, cerebellum, and anterior pituitarygland. In this patient, the first to receive MnDPDP for therapy,an apparent palliation was at the cost of widespread brain deposi-tion of Mn caused by a far-too-high total dose of MnDPDP,advanced liver failure, and, possibly, a BBB weakened by diseaseor treatment.Most interesting, SI was maximal in the dentate nucleus andglobus pallidus, sites also noted for deposition of gadolinium(Gd) ions released from linear chelates.4 This finding may indi-cate a mutual, possibly calcium-related, pathway for storage ofMn and Gd adducts in the brain.REFERENCES1. Sudarshana DM, Nair G, Dewey B, et al.Manganese-enhanced MRI ofthe brain in healthy volunteers. AJNR Am J Neuroradiol 2019;40:1309–16 CrossRef Medline2. Karlsson JO, Ignarro LJ, Lundström I, et al. Calmangafodipir [Ca4Mn(DPDP)5], mangafodipir (MnDPDP) and MnPLED with special ref-erence to their SOD mimetic and therapeutic properties. Drug DiscovToday 2015;20:411–21 CrossRef Medline3. Yri OE, Vig J, Hegstad E, et al.Mangafodipir as cytoprotective adjunctto chemotherapy: a case report. Acta Oncol 2009;48:633–35 CrossRefMedline4. Kanda T, Nakai Y, Hagiwara A, et al.Distribution and chemical formsof gadolinium in the brain: a review. Br J Radiol 2017;90:20170115CrossRef MedlineV. BlomlieR. SivanandanDepartment of RadiologyInnlandet Trust Hospital, Gjøvik HospitalGjøvik, NorwayP. JyngeDepartment of RadiologyInnlandet Trust Hospital, Gjøvik HospitalGjøvik, NorwayNorwegian University of Science and TechnologyTrondheim, NorwayUniversity of LinkøpingLinkøping, SwedenFIG 1. Sagittal (T1-weighted-FLAIR) and axial (T1-weighted spin-echo)images show high SI reflecting Mn deposition in the corpus callosum(open arrow), mesencephalon, crus cerebri, dorsal brain stem, me-dulla oblongata (white arrows), cerebellum (dentate nucleus) (shortwhite arrow with cut), and basal ganglia (globus pallidus and puta-men) (long arrows with cut).Indicates open access to non-subscribers at www.ajnr.orghttp://dx.doi.org/10.3174/ajnr.A6347AJNR Am J Neuroradiol 41:E3 Jan 2020 www.ajnr.org E3

Manganese Uptake and Accumulation in the Human Brain

Blomlie, V.,

Sivanandan, R.,

Jynge, Per,

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https://sihf.brage.unit.no/sihf-xmlui/bitstream/11250/3122722/1/Manganese%2bUptake%2band%2bAccumulation%2bin%2bthe%2bHuman%2bBrain_Letter_Blomlie_2020.pdf

Manganese Uptake and Accumulation in the Human Brain

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