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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 1/2019

01-02-2019 | Research Article

The Value of In Vitro Binding as Predictor of In Vivo Results: A Case for [18F]FDDNP PET

Authors: Graham B. Cole, Nagichettiar Satyamurthy, Jie Liu, Koon-Pong Wong, Gary W. Small, Sung-Cheng Huang, Janez Košmrlj, Jorge R. Barrio, Andrej Petrič

Published in: Molecular Imaging and Biology | Issue 1/2019

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Abstract

Purpose

Caution is warranted when in vitro results of biomarkers labeled with tritium were perfunctorily used to criticize in vivo data and conclusions derived with the same tracers labeled with positron emitters and positron emission tomography (PET). This concept is illustrated herein with the PET utilization of [18F]FDDNP, a biomarker used for in vivo visualization of β-amyloid and tau protein neuroaggregates in humans, later contradicted by in vitro data reported with [3H]FDDNP. In this investigation, we analyze the multiple factors involved in the experimental design of the [3H]FDDNP in vitro study that led to the erroneous interpretation of results.

Procedure

The present work describes full details on the synthesis, characterization, purity, and kinetics of radiolytic stability of [3H]FDDNP. The optimal in vitro conditions for detecting tau and β-amyloid protein aggregates using macroscopic and microscopic autoradiography with both [18F]FDDNP and [3H]FDDNP are also presented. Macroscopic autoradiography determinations were performed with [3H]FDDNP of verified purity using established methods described previously in the literature.

Results

The autoradiographic results using phosphate buffered saline (PBS) with less than 1 % EtOH and pure, freshly prepared [3H]FDDNP compared with the earlier reported data using [3H]FDDNP of undetermined purity and PBS in 10 % EtOH demonstrate the critical importance of rigorous experimental design for meaningful in vitro determinations. [18F]FDDNP binding to both amyloid plaques and neurofibrillary tangles was confirmed by amyloid and tau immunohistochemical stains of adjacent tissues.

Conclusions

This work illustrates the sensitivity of in vitro techniques to various experimental conditions and underscores that conclusions obtained from translational in vitro to in vivo determinations must always be performed with extreme care to avoid wrong interpretations that can be perpetuated and assumed without further analysis.
Appendix
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Metadata
Title
The Value of In Vitro Binding as Predictor of In Vivo Results: A Case for [18F]FDDNP PET
Authors
Graham B. Cole
Nagichettiar Satyamurthy
Jie Liu
Koon-Pong Wong
Gary W. Small
Sung-Cheng Huang
Janez Košmrlj
Jorge R. Barrio
Andrej Petrič
Publication date
01-02-2019
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 1/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-018-1210-2

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