Preclinical Evaluation of Novel PET Probes for Dementia

Cools, Romy; Kerkhofs, Kobe; Bormans, Guy

doi:10.1053/j.semnuclmed.2023.03.004

Cited by 5 publications

(1 citation statement)

References 387 publications

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“…The successful development and use of diagnostic imaging agents, as outlined in Diagnostic imaging, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) based on small molecules (Figure 1) that easily cross the BBB have played a major role in understanding the development of Aβ plaques [11]. Over the last decade, the diagnostic imaging of Aβ plaques and related precursor components in the various stages of AD has made tremendous progress [12]. Information on the progression of AD at various Braak stages and the involvement of different brain regions has provided a wealth of information on relating the stages of the disease versus Aβ load [13].…”

Section: Introductionmentioning

confidence: 99%

[125I]IPC-Lecanemab: Synthesis and Evaluation of Aβ-Plaque-Binding Antibody and Comparison with Small-Molecule [18F]Flotaza and [125I]IBETA in Postmortem Human Alzheimer’s Disease

Liang,

Paclibar,

Gonzaga

et al. 2024

Neurology International

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Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of Aβ plaque load in AD has been underway and is now used in clinical studies. Here, we report our preliminary findings on imaging a therapeutic antibody, Lecanemab, in a postmortem AD brain anterior cingulate. [125I]5-iodo-3-pyridinecarboxamido-Lecanemab ([125I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([125I]iodo)-3-pyridinecarboxylate with Lecanemab in modest yields. The distinct binding of [125I]IPC-Lecanemab to Aβ-rich regions in postmortem human AD brains was higher in grey matter (GM) containing Aβ plaques compared to white matter (WM) (GM/WM was 1.6). Anti-Aβ immunostaining was correlated with [125I]IPC-Lecanemab regional binding in the postmortem AD human brains. [125I]IPC-Lecanemab binding was consistent with the binding of Aβ small molecules, [18F]flotaza and [125I]IBETA, in the same subjects. [18F]Flotaza and [125I]IBETA, however, exhibited significantly higher GM/WM ratios (>20) compared to [125I]IPC-Lecanemab. Our results suggest that radiolabeled [125I]IPC-Lecanemab retains the ability to bind to Aβ in human AD and may therefore be useful as a PET imaging radiotracer when labeled as [124I]IPC-Lecanemab. The ability to directly visualize in vivo a promising therapeutic antibody for AD may be useful in treatment planning and dosing and could be complimentary to small-molecule diagnostic imaging to assess outcomes of therapeutic interventions.

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Section: Introductionmentioning

confidence: 99%