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Methanobactin rapidly facilitates biliary copper excretion in a Wilson disease rat model visualised by 64Cu PET/MRI.
Br. J. Pharmacol., DOI: 10.1111/bph.70099 (2025)
BACKGROUND AND PURPOSE: Methanobactins are peptides with high copper affinity and potential to treat Wilson disease. We examined how two methanobactins (ARBM101 and MB-OB3b) affected copper handling in the LPP Atp7b-/- Wilson disease rat model, compared to penicillamine or saline, by 64Cu positron emission tomography/magnetic resonance imaging. Heterozygotes served as controls. EXPERIMENTAL APPROACH: 64Cu was administered i.v. to 19 LPP and four control rats. A baseline scan was performed 1 h later. LPP rats received one dose of saline, penicillamine, MB-OB3b or ARBM101 i.p. (t = 100 min), followed by a 90-min scan and a final scan at t = 24 h. Controls followed identical procedures without intervention. 64Cu levels were evaluated as % injected dose (%ID) in the liver, kidney and 'abdominal-pelvic region' (intestines and other non-hepatic, non-renal organs). KEY RESULTS: At baseline, hepatic %ID was ≈50% higher in LPP rats than in controls. Intraintestinal 64Cu activity, indicating biliary excretion, was present in controls and absent in LPP rats. After methanobactin injection (but not saline or penicillamine), 64Cu appeared in the small intestines of LPP rats within 10-15 min. Hepatic %ID increased over 24 h in saline-, penicillamine- and MB-OB3b-injected rats but decreased in control rats. ARBM101 almost normalised hepatic 64Cu at 24 h. CONCLUSIONS AND IMPLICATIONS: A single i.p. methanobactin dose restored biliary copper excretion in LPP rats. The effect was more pronounced with ARBM101 than with MB-OB3b. Non-ATP7B transporters must be involved because ATP7B is absent in LPP rats. Methanobactin may have therapeutic potential in Wilson disease.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Chelation Therapy ; Positron‐emission Tomography ; Copper Metabolism ; Copper‐binding Protein; Positron-emission-tomography; Therapy; Binding; Strain; Metabolism; Diagnosis; Efficacy; Gene
Language
english
Publication Year
2025
HGF-reported in Year
2025
ISSN (print) / ISBN
0007-1188
e-ISSN
1476-5381
Journal
British Journal of Pharmacology
Publisher
Wiley
Publishing Place
111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status
Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-505200-003
Grants
The Memorial Foundation of Manufacturer Vilhelm Pedersen and Wife
WOS ID
001561292200001
Scopus ID
105014732202
PubMed ID
40890927
Erfassungsdatum
2025-11-13