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Link to original content: http://pubmed.ncbi.nlm.nih.gov/39093479/
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. 2024 Aug 2;9(1):57.
doi: 10.1186/s41181-024-00288-6.

Cyclotron production of manganese-52: a promising avenue for multimodal PET/MRI imaging

Francesca Porto #  1 , Sara Cisternino #  2 , Emiliano Cazzola  3 , Giorgia Speltri  4 , Liliana Mou  2 , Alessandra Boschi  5 , Lorenza Marvelli  4 , Giovanni Di Domenico  6 , Antonella Pagnoni  4 , Lucia De Dominicis  2   7 , Irene Calliari  8 , Claudio Gennari  8 , Licia Uccelli  1 , Gaia Pupillo  2 , Giancarlo Gorgoni  3 , Juan Esposito #  2 , Petra Martini #  9
Affiliations

Cyclotron production of manganese-52: a promising avenue for multimodal PET/MRI imaging

Francesca Porto et al. EJNMMI Radiopharm Chem. .

Abstract

Background: The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) holds promise for advancing diagnostic imaging capabilities. The METRICS project aims to develop cyclotron-driven production of 52Mn for PET/MRI imaging.

Results: Using the 52Cr(p,n)52Mn reaction, we designed chromium metal targets via Spark Plasma Sintering and developed a separation procedure for isolating 52Mn. Labeling tests were conducted with traditional chelators (i.e. S-2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid) and the 1.4-dioxa-8-azaspiro[4.5]decane-8- carbodithioate ligand to produce radioactive complexes suitable for PET/MRI applications. Our methodology yielded high-quality 52Mn suitable for PET radiopharmaceuticals and PET/MRI imaging. Preliminary studies on phantom imaging using microPET and clinical MRI demonstrated the efficacy of our approach.

Conclusions: The developed technology offers a promising avenue for producing 52Mn and enhancing PET/MRI imaging capabilities. Further in vivo investigations are warranted to evaluate the potential advantages of this hybrid imaging technique.

Keywords: Cyclotron production; Ion exchange chromatography; Manganese-52; Mn-based contrast agents; Mn-radiopharmaceuticals; PET-imaging; PET/MRI; Spark plasma sintering.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
SEM image of natCr powder (left) and picture of the 52Cr fine sived powder (middle), and big powder particles (right)
Fig. 2
Fig. 2
SEM images of the 52Cr targets realized with sieved powder (left) and cryomilled powder (right)
Fig. 3
Fig. 3
Metallurgical interphase analysis of the target Cr-Au/Nb at different magnitudes: picture and SEM images of the cross-section view. The EDS line scanning is also reported
Fig. 4
Fig. 4
Scheme of the Cr/Mn separation procedure based on the use of two AG1-X8 anionic resin. 1.Loading a 3% HCl solution containing the mixture Cr/Mn on the anionic resin; 2. Washing with 25 mL of 3% HCl in EtOH; 3. Mn elution with 3 mL of HCl 0.1 M; Solvent evaporation and dissolution with 2 mL of HCl 37% and 64.5 mL of EtOH; 4. Loading on the second AG1-X8; 5. Washing with 20 mL of 3% HCl in EtOH; 6. Mn elution with 2 mL of HCl 0.1 M
Fig. 5
Fig. 5
Scheme of the Cr/Mn separation procedure combining an AG1X-8 resin with an AG50W-X4 resin. 1. Loading a 3% HCl solution containing the mixture Cr/Mn on the anionic resin; 2. Washing with 25 mL of 3% HCl in EtOH; 3. Mn elution with 3 mL of HCl 0.1 M and loading on the AG50W-X4 resin; 4. Washing with 35 mL HCl 0.1 M, 2 mL HCl 0.3 M and 0.2 mL HCl 1.5 M; 5. Mn elution with 2 mL of HCl 1.5 M
Fig. 6
Fig. 6
Automatic module assembly by using Eckert & Ziegler cassette-based modular units, on the left the dissolution reactor especially realized to fit the target as described by Sciacca et al.
Fig. 7
Fig. 7
Image of the HPGE γ-spectra of the product at EOP
Fig. 8
Fig. 8
Radiochemical purity (%RCP) of the [52Mn]Mn-DOTA-SCN compound obtained incubating [52Mn]MnCl2 with different concentrations of the ligand DOTA-SCN, and at different time
Fig. 9
Fig. 9
Spectrum of interacting photons into the PET detector. The two vertical lines indicate the energy window used to reconstruct the PET data, while the blue line separates the region below the peak of the 511 keV corresponding to the photons scattered by the region of the non-scattered photons
Fig. 10
Fig. 10
Reconstructed images form NEMA NU-4 image quality phantom. PET data was reconstructed with attenuation and scatter correction by using the iterative method: a a single sagittal slice is shown highlighting the different sections in the phantom; b a single transverse slice through the uniform section of phantom; c a single transverse slice through the section of the phantom containing air; and d a single transverse slice through the 5 rods region
Fig. 11
Fig. 11
T1-weighted MR images of glass tubes containing Gadobenato dimeglumina (A), Mn(II)Cl2 × 4H2O (B), [Mn(II)(DASD)2] × 2H2O (C) in water at concentrations 3 mM obtained with 1.5 T a clinical Siemens Magnetom Aera (Reale et al. 2023). Original picture
Fig. 12
Fig. 12
Image of the graphite press in the vacuum chamber during the Cr powder sintering
See this image and copyright information in PMC

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