Noninvasive Assessment of Elimination and Retention using CT-FMT and Kinetic Whole-body Modeling

Theranostics
Wa'el Al RawashdehFelix Gremse

Abstract

Fluorescence-mediated tomography (FMT) is a quantitative three-dimensional imaging technique for preclinical research applications. The combination with micro-computed tomography (µCT) enables improved reconstruction and analysis. The aim of this study is to assess the potential of µCT-FMT and kinetic modeling to determine elimination and retention of typical model drugs and drug delivery systems. We selected four fluorescent probes with different but well-known biodistribution and elimination routes: Indocyanine green (ICG), hydroxyapatite-binding OsteoSense (OS), biodegradable nanogels (NG) and microbubbles (MB). µCT-FMT scans were performed in twenty BALB/c nude mice (5 per group) at 0.25, 2, 4, 8, 24, 48 and 72 h after intravenous injection. Longitudinal organ curves were determined using interactive organ segmentation software and a pharmacokinetic whole-body model was implemented and applied to compute physiological parameters describing elimination and retention. ICG demonstrated high initial hepatic uptake which decreased rapidly while intestinal accumulation appeared for around 8 hours which is in line with the known direct uptake by hepatocytes followed by hepatobiliary elimination. Complete clearance from the body wa...Continue Reading

Citations

Oct 4, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Julia G MannheimMarc C Huisman
Dec 12, 2018·Advanced Materials·Weizhi Wang, Zhiyuan Hu
Dec 15, 2020·Methods and Applications in Fluorescence·Rania BelhadjhamidaKullervo Hynynen
Oct 4, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ilaria BiancacciAlexandros Marios Sofias
Jul 8, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Simin ZuoFelix Gremse

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