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Exploring a Mathematical Model for the Kinetics of β-Amyloid Molecular Imaging Probes through a Critical Analysis of Plaque Pathology

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Abstract

Amyloid plaques are highly heterogeneous in content, size, density, and macromolecular crowding, as they are composed of masses of fibrils and other cellular material. Given this target architecture, the aggregated microenvironment offers a unique imaging target for ligands and positron emission tomography (PET) molecular imaging probes (MIPs). In this work, we address how the heterogeneous microenvironment of a plaque and its evolution may affect the kinetic rate constant of PET MIPs. We argue that macromolecular crowding will result in anomalous diffusion within plaque regions. To account for anomalous diffusion within plaques, we propose a diffusion-limited ligand-receptor compartmental model. Given the current state of knowledge about the pathological progression of Alzheimer's disease (AD), the model's parameters may be a function of the pathological progression of AD, which could result in biased estimates of the true amyloid load. The bias may be partially overcome through evaluation in conjunction with other measures of AD progression including cerebral glucose metabolism rate, neuronal cell loss, and activated inflammatory presence.

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Authors and Affiliations

  1. Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA

    Kooresh Shoghi-Jadid & Sung-Cheng Huang

  2. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA

    Kooresh Shoghi-Jadid, Jorge R. Barrio, Vladimir Kepe & Sung-Cheng Huang

  3. UCLA-DOE Center for Molecular Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USA

    Jorge R. Barrio & Sung-Cheng Huang

  4. Division of Radiological Sciences, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO, 63110, USA

    Kooresh Shoghi-Jadid

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  1. Kooresh Shoghi-Jadid
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  2. Jorge R. Barrio
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Correspondence to Kooresh Shoghi-Jadid.

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Shoghi-Jadid, K., Barrio, J.R., Kepe, V. et al. Exploring a Mathematical Model for the Kinetics of β-Amyloid Molecular Imaging Probes through a Critical Analysis of Plaque Pathology. Mol Imaging Biol 8, 151–162 (2006). https://doi.org/10.1007/s11307-006-0037-4

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  • DOI: https://doi.org/10.1007/s11307-006-0037-4

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