Manganese in <scp>PET</scp> imaging: Opportunities and challenges

Brandt, Marie; Cardinale, Jens; Rausch, Ivo; Mindt, Thomas L.

doi:10.1002/jlcr.3754

Cited by 30 publications

(31 citation statements)

References 61 publications

(61 reference statements)

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“…The effect of the contamination by 53 Mn on the total dose released to the patient has not been carefully analyzed yet [1], but it should be of minor importance due to its very long half-life. The very small activities reported in Tab.…”

Section: Comparison With Other Production Routesmentioning

confidence: 99%

“…For example, to obtain a combined PET/MRI scan with just one single radio-pharmaceutical, one must consider a β + emitting radionuclide which could be bound to a paramagnetic compound. Radionuclides that fits these characteristics are 52g Mn, 52m Mn, and 51 Mn [1]. We are interested here in the production of 52g Mn: its decay properties, and those of contaminants typically involved in the production methods, are reported in Tab.…”

Section: Introductionmentioning

confidence: 99%

“…The standard production routes of 52g Mn at cyclotrons are based on the following reactions: 52 Cr(p,n) 52g/m Mn, 53 Cr(p,2n) 52g/m Mn, and 54 Cr(p,3n) 52g/m Mn, which can be exploited at energies lower than 20 MeV or, even, with 16 MeV cyclotrons [1]. The use of natural Chromium targets has been extensively investigated: 52 Cr constitutes 84% of nat Cr, while 53 Cr is 10% and 54 Cr is 2%; the remaining 4%, made of 50 Cr, contributes only to contaminants production but not to the production of the radionuclide of interest.…”

Section: Introductionmentioning

confidence: 99%

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Production of high purity 52gMn from natV targets with α beams at cyclotrons

Colombi

Carante

Barbaro

et al. 2020

Preprint

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BackgroundRadioisotope 52g Mn is of special interest for multimodal imaging (PET/MRI) applications and the main production route is based on proton/deuteron beams on Chromium (natural/enriched) targets. Using state-of-art nuclear reaction codes (Talys, Empire and Fluka), we perform a comparative study with the alternative 52g Mn production with the reaction nat V(α,x) 52g Mn. ResultsThis production channel, novel in the context of medical applications, provides a good source of 52g Mn, where very high radionuclidic purity can be maintained up to 3 weeks. Since nat V consists already of 99.75% 51 V , there is no need of enriched target material and the corresponding high-cost implications. The production of the main long-lived contaminants, i:e: 53 Mn and 54 Mn, is considered with care and the integral yields of the reactions are compared with the alternative production routes. Specifically, the production of the 54 Mn contaminant, which could be the most dangerous for clinical applications, turns out to be lower when compared with the natural Chromium target. ConclusionsThis channel turns out competitive with respect to the other considered production routes. The study also reveals poor accuracy of the relevant cross-section data set and indicates that better data and theoretical descriptions are needed for a precise evaluation of nat V(α,x) 52g Mn.

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Section: Comparison With Other Production Routesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Production of high purity 52gMn from natV targets with α beams at cyclotrons

Colombi

Carante

Barbaro

et al. 2020

Preprint

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“…Like Gd(III), manganese(II) is paramagnetic and shortens T1 relaxation times, but manganese-based contrast agents have lower relaxivities (i.e., produce a smaller decrease in T1 per unit of contrast agent concentration) than GBCAs (Brandt et al, 2019). Unlike…”

Section: Introductionmentioning

confidence: 99%

In vivomulti-parametric manganese-enhanced MRI for detecting senile plaques in rodent models of Alzheimer’s disease

Kim

Censo

Baraldo

et al. 2021

Preprint

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Senile plaques are a hallmark of Alzheimer’s disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats.Fourteen mice (eight transgenic, six wild-type) and eight rats (four transgenic, four wild-type) were given subcutaneous injections of MnCl2 and imaged in vivo using a 9.4T Bruker scanner. Susceptibility-weighted images, transverse relaxation rate (R2*) maps, and quantitative susceptibility maps were derived from high-resolution 3D multi-gradient-echo (MGE) data to directly visualize plaques. Longitudinal relaxation rate (R1) maps were derived from MP2RAGE data to measure regional manganese uptake. After scanning, the brains were processed for histology and stained for beta-amyloid (4G8 antibody), iron (Perl’s), and calcium/manganese (Alizarin Red).MnCl2 improved signal-to-noise ratio (1.55±0.39-fold increase in MGE images) as expected, although this was not necessary for detection of plaques in the high-resolution images. Plaques were visible in susceptibility-weighted images, R2* maps, and quantitative susceptibility maps, with increased R2* and more positive magnetic susceptibility compared to surrounding tissue.In the 5xFAD mice, most MR-visible plaques were in the hippocampus, though histology confirmed plaques in the cortex and thalamus as well. In the TgF344-AD rats, many more plaques were MR-visible throughout the hippocampus and cortex. Beta-amyloid and iron staining indicate that, in both models, MR visibility was driven by plaque size and iron load.Voxel-wise comparison of R1 maps revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. Interestingly, in contrast to plaque visibility in the high-resolution images, the increased manganese uptake was limited to the rhinencephalon in the TgF344-AD rats (family-wise error (FWE)-corrected p < 0.05) while it was most significantly increased in the cortex of the 5xFAD mice (FWE-corrected p < 0.3). Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats.Multi-parametric MEMRI is a simple, viable method for detecting senile plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.HighlightsThis is the first study to use manganese-enhanced MRI (MEMRI) for direct visualization of senile plaques in rodent models of Alzheimer’s disease, in vivo.Manganese enhancement is not necessary to detect plaques but improves image contrast and signal-to-noise ratio.Manganese binds to plaques in 5xFAD mice but not in TgF344-AD rats, demonstrating potential as a targeted contrast agent for imaging plaques in certain models of AD.

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“…Eminent reviews covering oncological imaging and therapy approaches using CAR modified T cells, which already found the way into the clinics, exotic radionuclides such as those from manganese, or the progress in the development of imaging probes for the GluN2A subunit complete this special issue.…”

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confidence: 99%

Editorial for the special Issue “Jörg Steinbach”

Mamat

2019

Labelled Comp Radiopharmac

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This special issue of Journal of Labelled Compounds and Radiopharmaceuticals is dedicated to commemorate the outstanding scientific work of Jörg Steinbach, former director of the Institute of Radiopharmaceutical Cancer Research at the Helmholtz‐Zentrum Dresden‐Rossendorf (HZDR) and full professor for Bioinorganic and Radiopharmaceutical Chemistry at the Technical University Dresden. Current legal regulations brought to an end the formal attachment of Professor Steinbach to the TU Dresden as well as the directorship of the institute within his 65th birthday. A festive symposium has been held at the HZDR on the occasion of his retirement on September 5th, 2018, one day after the inauguration of the new Centre for Radiopharmaceutical Tumor Research at the HZDR.

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Manganese in PET imaging: Opportunities and challenges

Cited by 30 publications

References 61 publications

Production of high purity 52gMn from natV targets with α beams at cyclotrons

Production of high purity 52gMn from natV targets with α beams at cyclotrons

In vivomulti-parametric manganese-enhanced MRI for detecting senile plaques in rodent models of Alzheimer’s disease

Editorial for the special Issue “Jörg Steinbach”

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