Alzheimer s & Dementia,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 8, 2025
Abstract
INTRODUCTION
The
Alzheimer's
Association
and
the
Society
of
Nuclear
Medicine
Molecular
Imaging
convened
a
multidisciplinary
workgroup
to
update
appropriate
use
criteria
(AUC)
for
amyloid
positron
emission
tomography
(PET)
develop
AUC
tau
PET.
METHODS
identified
key
research
questions
that
guided
systematic
literature
review
on
clinical
amyloid/tau
Building
this
review,
developed
17
scenarios
in
which
or
PET
may
be
considered.
A
modified
Delphi
approach
was
used
rate
each
scenario
by
consensus
as
“rarely
appropriate,”
“uncertain,”
“appropriate.”
Ratings
were
performed
separately
stand‐alone
modalities.
RESULTS
For
PET,
seven
rated
appropriate,
two
uncertain,
eight
rarely
appropriate.
five
six
DISCUSSION
provide
expert
recommendations
these
technologies
evolving
landscape
diagnostics
therapeutics
disease.
Highlights
updated
goal
is
assist
clinicians
identifying
useful
guiding
diagnosis
management
patients
who
have,
are
at
risk
for,
cognitive
decline
These
intended
dementia
specialists
spend
significant
proportion
their
effort
caring
with
complaints,
well
serve
general
reference
broader
audience
interested
implementation
practice.
Journal of Nuclear Medicine,
Год журнала:
2025,
Номер
unknown, С. jnumed.124.268756 - jnumed.124.268756
Опубликована: Янв. 8, 2025
The
Alzheimer's
Association
and
the
Society
of
Nuclear
Medicine
Molecular
Imaging
convened
a
multidisciplinary
workgroup
to
update
appropriate
use
criteria
(AUC)
for
amyloid
positron
emission
tomography
(PET)
develop
AUC
tau
PET.
Methods:
identified
key
research
questions
that
guided
systematic
literature
review
on
clinical
amyloid/tau
Building
this
review,
developed
17
scenarios
in
which
or
PET
may
be
considered.
A
modified
Delphi
approach
was
used
rate
each
scenario
by
consensus
as
"rarely
appropriate,"
"uncertain,"
"appropriate."
Ratings
were
performed
separately
stand-alone
modalities.
Results:
For
PET,
7
rated
appropriate,
2
uncertain,
8
rarely
appropriate.
5
6
Conclusion:
provide
expert
recommendations
these
technologies
evolving
landscape
diagnostics
therapeutics
disease.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 9, 2025
Molecular
rotor-based
fluorophores
(RBFs)
that
are
target-selective
and
sensitive
to
both
polarity
viscosity
valuable
for
diverse
biological
applications.
Here,
we
have
designed
next-generation
RBFs
based
on
the
underexplored
bimane
fluorophore
through
either
changing
in
aryl
substitution
or
varying
π-linkages
between
rotatable
electron
donors
acceptors
produce
red-shifted
fluorescence
emissions
with
large
Stokes
shifts.
exhibit
a
twisted
intramolecular
charge
transfer
mechanism
enables
control
of
sensitivity,
as
well
target
selectivity.
These
features
enable
their
application
in:
(1)
turn-on
fluorescent
detection
α-synuclein
(αS)
fibrils,
hallmark
Parkinson's
disease
(PD),
including
amplified
fibrils
from
patient
samples;
(2)
monitoring
early
misfolding
oligomer
formation
during
αS
aggregation;
(3)
selective
imaging
condensates
formed
by
liquid-liquid
phase
separation
(LLPS).
In
all
three
cases,
show
our
probes
high
levels
selectivity
versus
other
aggregating
proteins.
properties
one
study
interplay
tau
amyloid
aggregation
mechanisms
underlying
neurodegenerative
disorders.
American Journal of Roentgenology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 16, 2025
Amyloid
and
tau
PET
have
contributed
significantly
to
understanding
the
biology
of
Alzheimer
disease
(AD),
aided
development
biomarker-driven
AD
diagnostic
criteria,
facilitated
approval
first
disease-modifying
drugs
for
AD.
As
opportunities
use
amyloid
in
clinic
expanded,
several
factors
will
impact
their
application
real-world
patients
with
First,
quantification
interpretations,
supported
by
appropriate
visual
confirmation,
be
needed
monitoring
therapy
response.
Also,
need
balanced
emerging
biofluid
assays
from
CSF
blood.
Blood-based
biomarkers,
although
still
requiring
validation,
particular
potential
complement
utilization;
nonetheless,
topographic
information
uniquely
provided
remain
important
clinical
practice.
Additionally,
proper
management
require
an
consideration
mixed
pathology,
as
is
usually
present
AD,
along
continued
advances
imaging
technology
better
address
copathology.
Further
research
investment
this
evolving
field
improve
accuracy
therapeutic
approaches,
ultimately
benefiting
outcomes
Chemistry - A European Journal,
Год журнала:
2024,
Номер
30(23)
Опубликована: Фев. 14, 2024
Abstract
Aggregated
α‐synuclein
(α‐syn)
protein
is
a
pathological
hallmark
of
Parkinson's
disease
(PD)
and
Lewy
body
dementia
(LBD).
Development
positron
emission
tomography
(PET)
radiotracers
to
image
α‐syn
aggregates
has
been
longstanding
goal.
This
work
explores
the
suitability
pyridothiophene
scaffold
for
PET
radiotracers,
where
47
derivatives
potent
(asyn‐44;
K
d
=1.85
nM)
were
synthesized
screened
against
[
3
H]asyn‐44
in
competitive
binding
assays
using
post‐mortem
PD
brain
homogenates.
Equilibrium
inhibition
constant
(K
i
)
values
most
compounds
determined,
which
three
had
′s
lower
nanomolar
range
(12–15
nM).
An
autoradiography
study
confirmed
that
promising
imaging
sections
from
multiple
system
atrophy
donors.
Fluorine‐18
labelled
asyn‐44
was
6±2
%
radiochemical
yield
(decay‐corrected,
n=5)
with
molar
activity
263±121
GBq/μmol.
Preliminary
18
F]asyn‐44
rats
showed
high
initial
uptake
(>1.5
standardized
value
(SUV)),
moderate
washout
(~0.4
SUV
at
60
min),
low
variability.
Radiometabolite
analysis
60–80
parent
tracer
after
30
mins.
While
displayed
good
vitro
properties
acceptable
uptake,
troublesome
radiometabolites
precluded
further
studies.
The
synthesis
evaluation
additional
are
underway,
goal
attaining
improved
affinity
metabolic
stability.
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(15), С. 12695 - 12710
Опубликована: Июль 31, 2024
α-synuclein
(α-syn)
pathologies
are
central
to
the
development
of
synucleinopathies
including
Parkinson's
disease
(PD).
Positron
emission
tomography
(PET)
imaging
α-syn
is
one
strategy
facilitate
diagnosis,
understanding,
and
treatment
synucleinopathies,
but
has
been
restricted
by
lack
specific
PET
probes.
In
this
work,
we
identified
2,6-disubstituted
imidazo[2,1-b][1,3,4]thiadiazole
(ITA)
as
a
new
α-syn-binding
scaffold.
Through
autoradiography
studies,
discovered
an
iodinated
lead
compound
[125I]ITA-3,
with
moderate
binding
affinity
(IC50
=
55
nM)
in
human
PD
brain
sections.
Modified
from
developed
potential
tracer,
[18F]FITA-2
(radiochemical
yield
>25%,
molar
activity
>110
GBq/μmol),
which
demonstrated
clear
signals
α-syn-rich
regions
tissues
245
nM),
good
uptake
(SUVpeak
2.80
±
0.45),
fast
clearance
rate
rats.
Overall,
appears
be
promising
candidate
for
merits
further
development.
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(35)
Опубликована: Авг. 22, 2024
α-synuclein
(α-syn)
assembles
into
structurally
distinct
fibril
polymorphs
seen
in
different
synucleinopathies,
such
as
Parkinson’s
disease
and
multiple
system
atrophy.
Targeting
these
unique
structures
using
chemical
ligands
holds
diagnostic
significance
for
subtypes.
However,
the
molecular
mechanisms
governing
small
molecules
interacting
with
remain
unclear.
Here,
we
investigated
interactions
of
belonging
to
four
scaffolds,
α-syn
polymorphs.
Using
cryo-electron
microscopy,
determined
when
bound
fibrils
formed
by
E46K
mutant
compared
them
those
wild-type
fibrils.
Notably,
observed
that
exhibit
remarkable
binding
adaptability,
they
engage
sites
across
While
scaffold
primarily
steered
locations
geometries
on
specific
sites,
conjugated
functional
groups
further
refined
this
adaptable
fine-tuning
sites.
Overall,
our
finding
elucidates
adaptability
structures,
which
sheds
light
tracer
drug
developments
tailored
pathological
