The Value of In Vitro Binding as Predictor of In Vivo Results: A Case for [18F]FDDNP PET
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...
Saved in:
Published in | Molecular imaging and biology Vol. 21; no. 1; pp. 25 - 34 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.02.2019
Springer Nature B.V Springer |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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 [
18
F]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 [
3
H]FDDNP. In this investigation, we analyze the multiple factors involved in the experimental design of the [
3
H]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 [
3
H]FDDNP. The optimal
in vitro
conditions for detecting tau and β-amyloid protein aggregates using macroscopic and microscopic autoradiography with both [
18
F]FDDNP and [
3
H]FDDNP are also presented. Macroscopic autoradiography determinations were performed with [
3
H]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 [
3
H]FDDNP compared with the earlier reported data using [
3
H]FDDNP of undetermined purity and PBS in 10 % EtOH demonstrate the critical importance of rigorous experimental design for meaningful
in vitro
determinations. [
18
F]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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Undefined-2 FC03-87ER60615 USDOE Office of Science (SC) |
ISSN: | 1536-1632 1860-2002 |
DOI: | 10.1007/s11307-018-1210-2 |