SPECIAL

ARTICLE

A Comparison of FDG PET and IQNB SPECT in Normal Subjects and in Patients With Dementia Daniel R. Weinberger, M.D. Douglas Jones, Ph.D. Richard C. Reba, M.D. Ulricke Mann, M.D. Richard Coppola, D.Sc. Raymond Gibson, Ph.D. Julie Gorey, C.N.M.T. Allen Braun, M.D. Thomas N. Chase, M.D. Prior studies of patients with dementia have found similar qualitative patterns of cerebral glucose utilization with [18F12-fluoro-2-deoxyglucose (FDG) PET and of putative muscarinic receptor activity with P23113-quinuclidinyl-4-iodobenzilate (IQNB). This raised doubts about whether receptor binding determines IQNB distribution and whether clinical information in IQNB scans is unique. To compare the methods directly, 4 normal volunteers and 7 patients with dementia underwent FDG PET and high-resolution IQNB SPECT scans. In normal subjects, relative regional activity from the paired scans was only weakly correlated (r = 0.29). Some regions (e.g., thalamus, frontal cortex) showed a clear disassociation of activity. In de-

men ted patients,

IQNB scans tended to show larger defects than FDG scans, although one focal defect appeared only with PET. Results suggest that IQNB SPECT data are not primarily related to general physiological activity or regional cerebral blood flow and are not explained by attenuation or volume-averaging artifacts. Further studies should investigate whether IQNB scanning is a more sensitive in vivo measure of the extent of Alzheimer’s disease than is FDG PET. (The

Journal

Neurosciences

JOURNAL

of Neuropsychiatry 1992;

4:239-248)

OF NEUROPSYCHIATRY

and

Clinical

S

tudies of glucose metabolism cerebral blood flow (rCBF)

degenerative

dementia

of reduced

have

cortical

and studies of regional in patients with primary revealed

activity.

disease (AD) rior parietal

typically have and posterior

lesser

in the frontal cortex.7’8 (PD) primarily show

type

degree dementia

temporal of the

deficits

pattern

reduced temporal

in metabolism

physiological

defects

of clinical

characteristic

Patients

Alzheimer’s

activity

in the

cortex,

and

Patients frontal

and

ferentation,04

pattern that and

of intrinsic they reflect that

they

cortical cortical

are

location with

neuropathologicholinergic deaf-

a “partial

volume

artifact”

emission

puted

distribution

(SPECT)

scans

E1I]3-quinuc1idinyl-4-iodobenzilate finity antagonist of muscarinic

the

findings correspond to

resulting from focal tissue atrophy.15 We recently reported that single-photon tomography

to a

deficits.’#{176}12 Sev-

eral explanations for these pathophysiological have been suggested, including that they the regional cal lesions,2’”3

The

correlates

neuropsychological

infe-

with Pick’sand anterior

rCBF.9

usually

areas

with

of the

(IQNB), acetylcholine

showed focal areas of diminished radioligand in patients with dementia that were qualitatively

comof

a high-afreceptors, retention

similar

1991; accepted October 8, Branch, Intramural Research Program, National Institute of Mental Health, Neuroscience Center at St. Elizabeths; Division of Nuclear Medicine, George Washington University; and Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Washington, D.C. Address reprint requests to Dr. Weinberger, Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, Neuroscience Center at St. Elizabeths, Washington, DC 20032. Received 1991.

June

From

11,

1991;

the Clinical

revised

Brain

August

21,

Disorders

239

FDG

PET,

to the

IQNB

SPECT

general

IN DEMENTIA

pattern

of defects

found

rCBF

and

receptor

et al.’7 had

pre-

metabolic

with

glucose

metabolic

techniques.t6

viously

described

similar

results

in a single

though

the

findings

might

reflect

in the

density

IQNB

bility could consequence to partial pretation

of muscarinic

volume of IQNB

that

that

derived

metabolism

images

the resultant from

the possi-

because

study

with

both (FDG)

was

to partial

volume

probably

not

glucose “resting”

due

metabolism brain’8

disease,’9

regional

FDG

probably

data

1.

artifacts, to this

different

To the

correlates and

differences reflect

with

in patients between differentiation

tracers

thought

critical

in evaluating

to image

from

in vivo unrelated

their

rCBF

and

regional

comparison cerebral

potential

of radioprocesses

differential

is

clinical

METHODS Normal

of glucose

IQNB SPECT PET, we could

differences artifact.

affinity

A direct

utility.

Five paid

address some of individuals and

data from techniques

and/or

activity.

we could

scanning

was devised to By studying normal

density

a

the inter-

is qualitative, information

pare directly the qualitative niques. To the extent that both

240

reductions

they were primarily in rCBF or secondary

physiological

patients with dementia L’8F12-fluoro-2-deoxyglucose

FIGURE

Al-

or of rCBF.

The present these uncertainties.

bral mal,

focal

Moreover,

artifact. SPECT

patient.

density,

receptor

not be excluded that of regional variations

not be certain from

Holman

and com-

the two techmay be prone in

the

extent

data that

are cere-

rCBF in the norwith ALzheimer’s the

IQNB

of muscarinic

and

Subjects

normal male respondents

tutes of Health the study. They psychiatric

informed disclosure

volunteers (mean to advertisements normal volunteer had no history

illness

and

were

age 69, range in the National

49-83),

Insti-

office, participated of significant medical

medication

consent to participate of associated hazards

free.

Each

in this study and discomforts.

in or gave

after

full

Patients Participating

in the

cal diagnosis

of AD

(two

women,

three

two

with

a clinical

diagnosis

62, range

48-82),

study

were

five

degenerative dementia suggestive 65, one woman age 57), and one

patients

with

men;

a clini-

mean

age

of primary

of PD (one patient with

man age dementia

Selected images through the basal ganglia (“BG slice,” left half of figure) and the cortex (“cingulate slice”) of a normal volunteer showing computerized placement of region of interest template on MRI scans (upper row) on FDG PET scans (lower row, first and third images), and on IQNB SPECT scans (lower row, second and fourth images). Color bar is keyed to normalized activity as described in text (p. 242). FDG = t18FJ2-fluosn-2-deoxyglucose; IQNB = ImII3-quinuclidinyl-4-iodobenzilate.

VOLUME

4

#{149} NUMBER

3

#{149} SUMMER

1992

et at.

WEINBERGER

and 26).

cerebral gliosis Each had been

of uncertain etiology (a woman, age followed in the outpatient clinics of

the National Institutes Diagnosis was based a history tion

of Health on DSM-Ill-R

of gradually

without

laboratory

motor

MRI

intellectual

or sensory

examination

and/or

for other

were

negative

dementia.

The

clinical diagnosis ventriculomegaly tissue dence case.

patient

a 2-year

period.

lobar

atrophy

sonality change nitive deterioration, deficits

out

and

Hachinski

suggestive

tion. Each test battery

patient that

on

MRI

no specific

MRI

diffuse loss of

scans

per-

score2#{176}for less

scan,

evi-

than by the

4 in each presence

a history

of per-

to the extent of cogof neuropsychological

of prominent

frontal

lobe

matic four

scanning

25

scanner

detector

box

true

ness,

gap

10-mm

contiguous

For and

was

committee.

the

SPECT

Scan

Iodine-123

was

prepared

eliminates synthesized

contamination using the

by

the

with Wallach

cific activity was determined averaged 660 Ci/mmol. Each mately 5 mCi IQNB riod of 1 to 2 minutes

by

(p,5n)

with tory and

was Spe-

for each synthesis and subject received approxi-

intravenous while seated

injection with eyes drug were for this

solution.

Subjects

for approximately then went home.

2 hours

SPECT

scan

remained after

observed. dose from

in the

drug

performed

labora-

administration

the

following

day

approximately subjects were

21 hours after radioligand injection. The seated in a semireclined position in a com-

fortable dental head into the

chair, scanner

which gantry.

with

marker

lights

external

parallel

JOURNAL

to and

OF

at set

distances

NEUROPSYCHIATRY

was then raised After positioning to set the from

750,000

the

first

scan,

each

channel phantom

method

to each scan. Correction iodine-123 over the time (typically

of Kay

and

attenucorrec-

The optimum scanner was

value deter-

the value

iodine-123.

were

by counting background

for

of the

scans

the

for

used

in the

magnitude

by reconstructing

of 80

constant

traversed

the

to each projection. constant for our

profile

was

an attenuation

projection

corrections basis and

sequences

the

approximating and choosing

uniform

time

per slice). A stanthat includes at-

corrections

employs

the

the head yielded 8

acquisition

counts algorithm

correction, This

tion factor applied for the attenuation

of a uniform

geometry of that yielded

the the

Uniformity

applied

on

a uniform count rates

and

a channel-by-

iodine-123 immediately

flood prior

was also made for the decay of interval separating the two scan

3-4%).

FDG PET Scan Procedure All subjects

to bring the the head

angle

of the

the

canthomeatal

slices

underwent

a standard

an average of 11.5 months months, 2.8, was not reflected greater in the

uptake cingulate

both in

of normal

in left

10%

of the

0.04). This focal PET data, where