Dataset Information

In Vivo Amyloid-? Imaging in the APPPS1-21 Transgenic Mouse Model with a (89)Zr-Labeled Monoclonal Antibody.

ABSTRACT:

Introduction

The accumulation of amyloid-? is a pathological hallmark of Alzheimer's disease and is a target for molecular imaging probes to aid in diagnosis and disease monitoring. This study evaluated the feasibility of using a radiolabeled monoclonal anti-amyloid-? antibody (JRF/A?N/25) to non-invasively assess amyloid-? burden in aged transgenic mice (APPPS1-21) with ?PET imaging.

Methods

We investigated the antibody JRF/A?N/25 that binds to full-length A?. JRF/A?N/25 was radiolabeled with a [(89)Zr]-desferal chelate and intravenously injected into 12-13 month aged APPPS1-21 mice and their wild-type (WT) controls. Mice underwent in vivo ?PET imaging at 2, 4, and 7 days post injection and were sacrificed at the end of each time point to assess brain penetrance, plaque labeling, biodistribution, and tracer stability. To confirm imaging specificity we also evaluated brain uptake of a non-amyloid targeting [(89)Zr]-labeled antibody (trastuzumab) as a negative control, additionally we performed a competitive blocking study with non-radiolabeled Df-Bz-JRF/A?N/25 and finally we assessed the possible confounding effects of blood retention.

Results

Voxel-wise analysis of ?PET data demonstrated significant [(89)Zr]-Df-Bz-JRF/A?N/25 retention in APPPS1-21 mice at all time points investigated. With ex vivo measures of radioactivity, significantly higher retention of [(89)Zr]-Df-Bz-JRF/A?N/25 was found at 4 and 7 days pi in APPPS1-21 mice. Despite the observed genotypic differences, comparisons with immunohistochemistry revealed that in vivo plaque labeling was low. Furthermore, pre-treatment with Df-Bz-JRF/A?N/25 only partially blocked [(89)Zr]-Df-Bz-JRF/A?N/25 uptake indicative of a high contribution of non-specific binding.

Conclusion

Amyloid plaques were detected in vivo with a radiolabeled monoclonal anti-amyloid antibody. The low brain penetrance of the antibody in addition to non-specific binding prevented an accurate estimation of plaque burden. However, it should be noted that [(89)Zr]-Df-Bz-JRF/A?N/25 nevertheless demonstrated in vivo binding and strategies to increase brain penetrance would likely achieve better results.

SUBMITTER: Waldron AM

PROVIDER: S-EPMC4815004 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

In Vivo Amyloid-β Imaging in the APPPS1-21 Transgenic Mouse Model with a (89)Zr-Labeled Monoclonal Antibody.

Waldron Ann-Marie AM Fissers Jens J Van Eetveldt Annemie A Van Broeck Bianca B Mercken Marc M Pemberton Darrel J DJ Van Der Veken Pieter P Augustyns Koen K Joossens Jurgen J Stroobants Sigrid S Dedeurwaerdere Stefanie S Wyffels Leonie L Staelens Steven S

Frontiers in aging neuroscience 20160331

<h4>Introduction</h4>The accumulation of amyloid-β is a pathological hallmark of Alzheimer's disease and is a target for molecular imaging probes to aid in diagnosis and disease monitoring. This study evaluated the feasibility of using a radiolabeled monoclonal anti-amyloid-β antibody (JRF/AβN/25) to non-invasively assess amyloid-β burden in aged transgenic mice (APPPS1-21) with μPET imaging.<h4>Methods</h4>We investigated the antibody JRF/AβN/25 that binds to full-length Aβ. JRF/AβN/25 was radi ...[more]

PMID: 27064204

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