⁵²Mn production for PET/MRI tracking of human stem cells expressing divalent metal transporter 1 (DMT1)

There is a growing demand for long-term in vivo stem cell imaging for assessing cell therapy techniques and guiding therapeutic decisions. This work develops the production of ⁵²Mn and establishes proof of concept for the use of divalent metal transporter 1 (DMT1) as a positron emission tomography (PET) and magnetic resonance imaging (MRI) reporter gene for stem cell tracking in the rat brain. ⁵²Mn was produced via proton irradiation of a natural chromium target. In a comparison of two ⁵²Mn separation methods, solvent-solvent extraction was preferred over ion exchange chromatography because of reduced chromium impurities and higher ⁵²Mn recovery. In vitro uptake of Mn-based PET and MRI contrast agents (⁵²Mn²⁺ and Mn²⁺, respectively) was enhanced in DMT1 over-expressing human neural progenitor cells (hNPC-DMT1) compared to wild-type control cells (hNPC-WT). After cell transplantation in the rat striatum, increased uptake of Mn-based contrast agents in grafted hNPC-DMT1 was detected in in vivo manganese-enhanced MRI (MEMRI) and ex vivo PET and autoradiography. These initial studies indicate that this approach holds promise for dual-modality PET/MR tracking of transplanted stem cells in the central nervous system and prompt further investigation into the clinical applicability of this technique.