In Vitro and in Vivo Correlations of Fluorescent or Radioisotope Glucose-Analogs in Imaging Cancer Metabolism
Year: 2022
Type: preprint
Abstract: Molecular Imaging (MI) has become a versatile, indispensable tool in clinical and research settings for disease diagnostics. It can be largely divided into nuclear imaging and fluorescence imaging based on types of tracers involved. However, direct comparisons of both types of tracers in both in vivo and in vitro settings have not been extensively investigated. In particular, how the image-enabling modifications of innate metabolic biomolecules influence the imaging of the actual metabolism is a critical issue in MI. We compared the performances of fluorescent glucose-analog tracers, 2-NBDG and 2-DG-750, against radio-labeled tracer 18 F-FDG for cancer metabolism imaging in both in vitro and in vivo settings, to gain insight into the correlation between these settings, as well as how each image-labeling alter the localization and the metabolic functionality of the imaging biomolecules. In vitro cellular uptakes of 18 F-FDG, 2-NBDG, and 2-DG-750 in four cancer cell lines that possess different glucose uptake characteristics were quantitatively evaluated by fluorescence signals or gamma counters. The three tracers showed different internalization behaviors that seem to correlate with the size and type of the imaging label, and 18 F-FDG had the highest uptake. In vivo imaging of subcutaneous tumor xenograft murine models with positron emission tomography (PET) or whole-animal fluorescence imaging were also performed using the three tracers, and it was found that the ability to be internalized into the cells correlated with the specificity and resolution of cancer metabolic imaging. For example, the hydrophobic and bulky 2-DG-750 had low uptake by cells and displayed poor capabilities in term of imaging glucose metabolism in tumors compared to 18 F-FDG, which demonstrated rapid and localized accumulation as well as clearance. The results from this study demonstrate that although fluorescent molecules can accumulate in tumors due to hydrophobic interactions and possible aggregations at the tumor site, they are unable to be metabolized efficiently and not suitable for imaging the metabolic phenomena, compared with radio-labeled biomolecules that are free of these limitations. Although nuclear imaging has some impracticalities, they hold vast potentials for capturing accurate biological phenomena that will be crucial for future advances in the clinical and research settings.
Source: Research Square
Authors: Hongchang Lin, Mariko Kobayashi, Keiichiro Kushiro, Hironobu Yanagie, Kenji Shimazoe, Hiroyuki Takahashi
Institution: The University of Tokyo
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4297884531