Antibody-Based In Vivo PET Imaging Detects Amyloid-β Reduction in Alzheimer Transgenic Mice After BACE-1 Inhibition

Topic: Amyloid, tau and blood-test diagnosis

The concentration of 124 I-RmAb158-scFv8D3, as measured in vivo with PET, increased with age and corresponded well with the ex vivo autoradiography and Aβ immunohistochemistry results. Mice treated with NB-360 showed significantly lower in vivo PET signals than untreated animals and were similar to the baseline animals. The decreased 124 I-RmAb158-scFv8D3 concentrations in NB-360-treated mice, as quantified with PET, corresponded well with the decreased Aβ levels measured in postmortem brain. Several treatments for AD are in phase 2 and 3 clinical trials, but the possibility of studying treatment effects in vivo on the important, nonfibrillar, forms of Aβ is limited. This study demonstrated the ability of the Aβ protofibril-selective radioligand 124 I-RmAb158-scFv8D3 to follow disease progression and detect treatment effects with PET imaging in tg-ArcSwe mice.

@article{meier2018-29853653,
  author  = {Meier, SR. and Syvänen, S. and Hultqvist, G. and Fang, X. T. and Roshanbin, S. and Lannfelt, L. and Neumann, U. and Sehlin, D.},
  title   = {{Antibody-Based In Vivo PET Imaging Detects Amyloid-β Reduction in Alzheimer Transgenic Mice After BACE-1 Inhibition}},
  journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
  year    = {2018},
  doi     = {10.2967/jnumed.118.213140},
  pmid    = {29853653},
  url     = {https://doi.org/10.2967/jnumed.118.213140}
}

Key findings

• The concentration of 124 I-RmAb158-scFv8D3, as measured in vivo with PET, increased with age and corresponded well with the ex vivo autoradiography and Aβ immunohistochemistry results.
• Mice treated with NB-360 showed significantly lower in vivo PET signals than untreated animals and were similar to the baseline animals.
• The decreased 124 I-RmAb158-scFv8D3 concentrations in NB-360-treated mice, as quantified with PET, corresponded well with the decreased Aβ levels measured in postmortem brain.
• Several treatments for AD are in phase 2 and 3 clinical trials, but the possibility of studying treatment effects in vivo on the important, nonfibrillar, forms of Aβ is limited.
• This study demonstrated the ability of the Aβ protofibril-selective radioligand 124 I-RmAb158-scFv8D3 to follow disease progression and detect treatment effects with PET imaging in tg-ArcSwe mice.

Why it matters

In Alzheimer transgenic mice, PET imaging with the Aβ protofibril-selective radioligand 124I-RmAb158-scFv8D3 detected lower signals in mice treated with the BACE-1 inhibitor NB-360 than in untreated animals, matching decreased Aβ levels measured after death. This shows the imaging method can follow disease progression and detect treatment effects in these mice, but it is an animal study and does not show a treatment or cure for people.

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Study details

• Study designclinical trial
• Evidence strengthLow

Read the original

• DOI: 10.2967/jnumed.118.213140
• PubMed: 29853653
• Original source →
• Free full text: PubMed Central →

Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Alzheimer's Disease: The Amyloid Cascade Hypothesis Science · 1992-04-10 · usefulness score 61/100 · Disease mechanisms
• The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease Nature · 2016-08-30 · usefulness score 60/100 · Treatments
• Amyloid-β oligomerization in Alzheimer dementia versus high-pathology controls Annals of neurology · 2012-12-07 · usefulness score 52/100 · Risk genes beyond APOE
• Drug candidates in clinical trials for Alzheimer's disease Journal of biomedical science · 2017-07-19 · usefulness score 50/100 · Inflammation and the immune system
• Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers Neurology · 2012-06-13 · usefulness score 49/100 · Brain scans and imaging
• Evaluation of Small-Animal PET Outcome Measures to Detect Disease Modification Induced by BACE Inhibition in a Transgenic Mouse Model of Alzheimer Disease Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2017-06-13 · usefulness score 36/100 · Drug development

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• Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein Neuroscience · 1999-04-01 · usefulness score 45/100
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