VOL.
No.
125,
a
Downloaded from www.ajronline.org by 14.167.17.224 on 06/20/16 from IP address 14.167.17.224. Copyright ARRS. For personal use only; all rights reserved
A NEW
CONTRAST MEDIUM CHOLECYSTOGRAPHY IODOXAMATE*
E. NICHOLAS HARVEY
By
SARGENT, I. MEYERS, NICOLOFF,
M.D.,t M.D.,t M.D.,
ANDRE RICHARD and LOUIS
LOS ANGELES,
FOR CHOLANGIOMEGLUMINE
:
SCHULMAN, B. GUTLER, T. DaFAZIO,
M.B., M.R.C.P., M.D.4 JOHN PH.D.
F.F.R.,t T.
CALIFORNIA
ABSTRACT:
A preliminary of
10
to
study cc.
30
of
of
I
8 patients
meglumine
cholangio-cholecystography, with
effects
io
persistent
and
a single
(Cholovue),
showed
no
significant
and only transient, minor the subsegmental and Good to excellent opacification 0.1 I cc./kg. (19.7 mg. iodine) appears to be a highly
intravenous contrast
injection medium
clinical
or
for
laboratory
changes with 30 cc. Early and major bile ducts and the gallwas obtained in all cases with to 0.59 cc./kg. (108 mg. iodine). effective agent for cholangio-
of
obtained. between iodoxamate
bolus a new
adverse
cc.,
20
visualization
bladder was doses ranging Meglumine
following
iodoxamate
cholecystography.
Ilvi EGLUMINE is venous
is
Research
tria
Squibb
contrast an
for
intraThe
original
development
Laboratories
Chimica Institute
Meglumine
of for
With
(Cholovuejj)
medium
cholangio-cholecystography.
compound the
iodoxamate
a new
of Bracco
Milan, Medical
iodoxamate
of
highly
soluble
metals
the
Preclinical
salts
water, and
with
evaluations in mice,
of rats
and
acute toxicity than meglumine ; thus, better
COOH
I
I
NHCO-[CH2CH2O]4-L
. Bis[N-Methylglucamine]
I 3,
S
From
the
Los
Angeles
3’-[(I,
16-Dioxo-4, diimino}
County-University
7, 10, I3-tetraoxahexadecane-I, bis [2, 4, 6-triiodobenzoic bis[N-methylglucamine]salt of Southern
California
Department
of Radiology,
Medical
Center,
i6-diyl)acid],
Los
Angeles,
California.
t
Department of Radiology. Department of Medicine. Present address: § Squibb Institute for Medical Research. Supported by a grant from Squibb Institute
II Squibb
Institute
for
Medical
Research,
for
Medical
Princeton,
Research, N.J. 251
University Princeton,
of Cape New
Jersey.
Town,
South
Africa.
are the
with
relatively
lodoxamate
II
that
permitting solutions
aqueous
to possess lower biliary excretion mide (Cholografin)
Meglumine
hydroxyalkyla-
forms
in of
iodoxamate
of 1,678.3 and a of 5.5 per cent. is as follows:
and
substance
high iodine content osmotic pressure.
is characterized
by a high molecular weight molecular iodine content The chemical composition
the
preparation
Indus-
Italy and Research.
alkaline
mines,
a low
meglumine dogs
show
and
better iodipatolerance
it
and
biliary
tract
visualization
are
The
I cc.
purpose
their
of the
preliminary
authors
is to present
experience
with
18
pa-
tients. MATERIAL
The of
selected
renal,
subjects
with
any
or
metabolic
from
of the
the
study.
study
were
with weeks
were
not
or
salicylates Included
to
16 asymptomatic,
oral and
had
with
body
weights kg., with
92.7
heights
average
an
face
areas
with
an
ranged
bowel residue
the
day
jects
with
the
examination.
prior
to
the
tion. A 40 per cent w/v aqueous solution of meglumine iodoxamate containing i 83 mg. of organically bound iodine per ml. was used for the intravenous bolus injection. The I 8 subjects studied were divided into 3 sub-groups: 6 of the subjects received 10
(3.66 ized
cc.
(1.83 gm.
gm. iodine)
gm. iodine), allocation.
iodine); ; and according
6 received 6
received to
20
cc.
30
cc.
a random-
the
contrast
obtained
again
injection
at
and
at
hours
hours,
4 hours,
trast
agent
administration.
were
observed
throughout
of
and
untoward
the minutes,
30 24
warmth,
flushing,
48,
24,
and
I 20
injection
urea
transami aminase;
hours
after
the
contrast
of
nitrogen;
serum
were and
the
albumin;
serum
intraagent:
glutamic-oxalic
total
cell
phosphate
serum
creatinine;
serum
serum
sodium;
chloride; creatinine
and
sured before and complete urinalysis these times.
and
lactic
decre-
glucose-6
(pre-injection
serum
serum clearance
after was
serum serum
cholinesterase;
dehydrogenase
serum Serum
dibilirubin;
serum
cholinesterase
only);
trans-
calcium; protein;
glucose;
phosphokinase; blood
serum
serum serum
serum
perat
including differserum uric acid;
serum
bilirubin;
hydrogenase;
atine
as a feeland skin
nase ; serum glu tamicpyruvic serum alkaline phosphatase;
serum cholesterol; phosphorus; total
red
examination
such nausea,
following laboratory tests just before the examination
serum
rect
conclusion of I hour, 2 after the conAll patients
the
reactions,
complete blood cell count, ential and platelet counts;
examina-
re-
The
venous
by ap-
pressure,
and an electrojust prior to the during 24 and signs
4, 8,
take nothing of water, for
blood
obtained of
performed
agent.
sur-
sub-
the
a full
electrocardiogram was monitored the entire procedure and repeated 120 hours after the procedure. Vital
cm.,
The
were
administration
191
a
and
over
were
Pulse,
body
but subject
hya slow
and were repeated at after injection of the
temperature,
The formed
used, each
examinations
injection 120 hours rate,
ing
m2,
was
bolus,
steadily
agent.
rashes.
2.21
see the
examination
single
spiratory
and The
m2 to
the
contrast
The
to
The
24
to
period.
for any 7
kg. kg.
68.6
was to
given
allowed to the exception 8 hours
proximately
2
of
8 and
of the
injected
of ac-
occurred,
A narrow-bore used to ensure
dose
the and
the
9 females i
for
of injection
were
and
31.8
cm.
cm.
from 1.41 I .7 m2.
preparation diet was
before
were
mouth,
of
367
study. were
years.
27.9
133
of
average
low
of
from
average
bar-
of visualization a double-dose
There were the ages of
required
minute
2,
minutes
reaction
was
1975
a test dose prior to the
waiting
adverse
cardiogram 4
month,
to the studied
varied between an average of
ranged
with
No
an
i
volunteers
failure following
cholecystogram. 9 males between
years,
the
any for
normal
patients who the gallbladder
a
treated
consume
for I week prior in the 18 subjects
After
given agent
intravenously. needle was
before
to par-
been
chlorpromazine
dose
Jo
ex-
from
had
total
rate
with
allowed
who
no
Physical
agents in the preceding examination. The subjects
permitted
biturates
were
excluded
subjects
any contrast before the
study.
that
allergy,
subject
was
tual
entire All
asthma,
No
thyroid
his-
hemato-
experience
Specifically
ticipate.
prior
disorders. of
hypertensive
disease
no
hepatic,
a history
cluded
or
had
subject was the contrast
of
injected podermic
METHOD
cardiovascular,
poietic, or
AND
subjects
tory
SEPTEMBER,
Each
possible
humans.
in
Downloaded from www.ajronline.org by 14.167.17.224 on 06/20/16 from IP address 14.167.17.224. Copyright ARRS. For personal use only; all rights reserved
et al.
Sargent
252
potassium;
carbon was
the also
dioxide. also mea-
procedure. performed
A at
Downloaded from www.ajronline.org by 14.167.17.224 on 06/20/16 from IP address 14.167.17.224. Copyright ARRS. For personal use only; all rights reserved
VOL.
No.
125,
Intravenous
a
Cholangio-Cholecystography
an average of 0.30 cc./kg. (55.14 rng. iodine/kg.). Table II shows the dose related to timing and duration of good to excellent opaciflcation (scores of 3 or 4). Good to excellent visualization of the bile ducts was noted as early as 10 minutes in 16 subjects (Fig. i), and as early as 20 to 30 minutes in 2 subjects. In most cases the bile ducts were opacifled immediately after the injection was completed (o time) (Fig. 2). Furthermore, the subsegmental biliary radicles were clearly seen without tomography, during the early stages of the examination (Fig. I ; and 2), often visible for as long as i hour after the injection (Fig. 3). In fact, persistence of the good-to-excellent visualization was found up to 6o minutes in all subjects. The grading of the quality of visualization of the biliary tract was subjected to statistical analysis. Based on an over-all score (obtained by averaging over io observation points), a statistically significant ( p
No.
125,
a
Downloaded from www.ajronline.org by 14.167.17.224 on 06/20/16 from IP address 14.167.17.224. Copyright ARRS. For personal use only; all rights reserved
A NEW
CONTRAST MEDIUM CHOLECYSTOGRAPHY IODOXAMATE*
E. NICHOLAS HARVEY
By
SARGENT, I. MEYERS, NICOLOFF,
M.D.,t M.D.,t M.D.,
ANDRE RICHARD and LOUIS
LOS ANGELES,
FOR CHOLANGIOMEGLUMINE
:
SCHULMAN, B. GUTLER, T. DaFAZIO,
M.B., M.R.C.P., M.D.4 JOHN PH.D.
F.F.R.,t T.
CALIFORNIA
ABSTRACT:
A preliminary of
10
to
study cc.
30
of
of
I
8 patients
meglumine
cholangio-cholecystography, with
effects
io
persistent
and
a single
(Cholovue),
showed
no
significant
and only transient, minor the subsegmental and Good to excellent opacification 0.1 I cc./kg. (19.7 mg. iodine) appears to be a highly
intravenous contrast
injection medium
clinical
or
for
laboratory
changes with 30 cc. Early and major bile ducts and the gallwas obtained in all cases with to 0.59 cc./kg. (108 mg. iodine). effective agent for cholangio-
of
obtained. between iodoxamate
bolus a new
adverse
cc.,
20
visualization
bladder was doses ranging Meglumine
following
iodoxamate
cholecystography.
Ilvi EGLUMINE is venous
is
Research
tria
Squibb
contrast an
for
intraThe
original
development
Laboratories
Chimica Institute
Meglumine
of for
With
(Cholovuejj)
medium
cholangio-cholecystography.
compound the
iodoxamate
a new
of Bracco
Milan, Medical
iodoxamate
of
highly
soluble
metals
the
Preclinical
salts
water, and
with
evaluations in mice,
of rats
and
acute toxicity than meglumine ; thus, better
COOH
I
I
NHCO-[CH2CH2O]4-L
. Bis[N-Methylglucamine]
I 3,
S
From
the
Los
Angeles
3’-[(I,
16-Dioxo-4, diimino}
County-University
7, 10, I3-tetraoxahexadecane-I, bis [2, 4, 6-triiodobenzoic bis[N-methylglucamine]salt of Southern
California
Department
of Radiology,
Medical
Center,
i6-diyl)acid],
Los
Angeles,
California.
t
Department of Radiology. Department of Medicine. Present address: § Squibb Institute for Medical Research. Supported by a grant from Squibb Institute
II Squibb
Institute
for
Medical
Research,
for
Medical
Princeton,
Research, N.J. 251
University Princeton,
of Cape New
Jersey.
Town,
South
Africa.
are the
with
relatively
lodoxamate
II
that
permitting solutions
aqueous
to possess lower biliary excretion mide (Cholografin)
Meglumine
hydroxyalkyla-
forms
in of
iodoxamate
of 1,678.3 and a of 5.5 per cent. is as follows:
and
substance
high iodine content osmotic pressure.
is characterized
by a high molecular weight molecular iodine content The chemical composition
the
preparation
Indus-
Italy and Research.
alkaline
mines,
a low
meglumine dogs
show
and
better iodipatolerance
it
and
biliary
tract
visualization
are
The
I cc.
purpose
their
of the
preliminary
authors
is to present
experience
with
18
pa-
tients. MATERIAL
The of
selected
renal,
subjects
with
any
or
metabolic
from
of the
the
study.
study
were
with weeks
were
not
or
salicylates Included
to
16 asymptomatic,
oral and
had
with
body
weights kg., with
92.7
heights
average
an
face
areas
with
an
ranged
bowel residue
the
day
jects
with
the
examination.
prior
to
the
tion. A 40 per cent w/v aqueous solution of meglumine iodoxamate containing i 83 mg. of organically bound iodine per ml. was used for the intravenous bolus injection. The I 8 subjects studied were divided into 3 sub-groups: 6 of the subjects received 10
(3.66 ized
cc.
(1.83 gm.
gm. iodine)
gm. iodine), allocation.
iodine); ; and according
6 received 6
received to
20
cc.
30
cc.
a random-
the
contrast
obtained
again
injection
at
and
at
hours
hours,
4 hours,
trast
agent
administration.
were
observed
throughout
of
and
untoward
the minutes,
30 24
warmth,
flushing,
48,
24,
and
I 20
injection
urea
transami aminase;
hours
after
the
contrast
of
nitrogen;
serum
were and
the
albumin;
serum
intraagent:
glutamic-oxalic
total
cell
phosphate
serum
creatinine;
serum
serum
sodium;
chloride; creatinine
and
sured before and complete urinalysis these times.
and
lactic
decre-
glucose-6
(pre-injection
serum
serum clearance
after was
serum serum
cholinesterase;
dehydrogenase
serum Serum
dibilirubin;
serum
cholinesterase
only);
trans-
calcium; protein;
glucose;
phosphokinase; blood
serum
serum serum
serum
perat
including differserum uric acid;
serum
bilirubin;
hydrogenase;
atine
as a feeland skin
nase ; serum glu tamicpyruvic serum alkaline phosphatase;
serum cholesterol; phosphorus; total
red
examination
such nausea,
following laboratory tests just before the examination
serum
rect
conclusion of I hour, 2 after the conAll patients
the
reactions,
complete blood cell count, ential and platelet counts;
examina-
re-
The
venous
by ap-
pressure,
and an electrojust prior to the during 24 and signs
4, 8,
take nothing of water, for
blood
obtained of
performed
agent.
sur-
sub-
the
a full
electrocardiogram was monitored the entire procedure and repeated 120 hours after the procedure. Vital
cm.,
The
were
administration
191
a
and
over
were
Pulse,
body
but subject
hya slow
and were repeated at after injection of the
temperature,
The formed
used, each
examinations
injection 120 hours rate,
ing
m2,
was
bolus,
steadily
agent.
rashes.
2.21
see the
examination
single
spiratory
and The
m2 to
the
contrast
The
to
The
24
to
period.
for any 7
kg. kg.
68.6
was to
given
allowed to the exception 8 hours
proximately
2
of
8 and
of the
injected
of ac-
occurred,
A narrow-bore used to ensure
dose
the and
the
9 females i
for
of injection
were
and
31.8
cm.
cm.
from 1.41 I .7 m2.
preparation diet was
before
were
mouth,
of
367
study. were
years.
27.9
133
of
average
low
of
from
average
bar-
of visualization a double-dose
There were the ages of
required
minute
2,
minutes
reaction
was
1975
a test dose prior to the
waiting
adverse
cardiogram 4
month,
to the studied
varied between an average of
ranged
with
No
an
i
volunteers
failure following
cholecystogram. 9 males between
years,
the
any for
normal
patients who the gallbladder
a
treated
consume
for I week prior in the 18 subjects
After
given agent
intravenously. needle was
before
to par-
been
chlorpromazine
dose
Jo
ex-
from
had
total
rate
with
allowed
who
no
Physical
agents in the preceding examination. The subjects
permitted
biturates
were
excluded
subjects
any contrast before the
study.
that
allergy,
subject
was
tual
entire All
asthma,
No
thyroid
his-
hemato-
experience
Specifically
ticipate.
prior
disorders. of
hypertensive
disease
no
hepatic,
a history
cluded
or
had
subject was the contrast
of
injected podermic
METHOD
cardiovascular,
poietic, or
AND
subjects
tory
SEPTEMBER,
Each
possible
humans.
in
Downloaded from www.ajronline.org by 14.167.17.224 on 06/20/16 from IP address 14.167.17.224. Copyright ARRS. For personal use only; all rights reserved
et al.
Sargent
252
potassium;
carbon was
the also
dioxide. also mea-
procedure. performed
A at
Downloaded from www.ajronline.org by 14.167.17.224 on 06/20/16 from IP address 14.167.17.224. Copyright ARRS. For personal use only; all rights reserved
VOL.
No.
125,
Intravenous
a
Cholangio-Cholecystography
an average of 0.30 cc./kg. (55.14 rng. iodine/kg.). Table II shows the dose related to timing and duration of good to excellent opaciflcation (scores of 3 or 4). Good to excellent visualization of the bile ducts was noted as early as 10 minutes in 16 subjects (Fig. i), and as early as 20 to 30 minutes in 2 subjects. In most cases the bile ducts were opacifled immediately after the injection was completed (o time) (Fig. 2). Furthermore, the subsegmental biliary radicles were clearly seen without tomography, during the early stages of the examination (Fig. I ; and 2), often visible for as long as i hour after the injection (Fig. 3). In fact, persistence of the good-to-excellent visualization was found up to 6o minutes in all subjects. The grading of the quality of visualization of the biliary tract was subjected to statistical analysis. Based on an over-all score (obtained by averaging over io observation points), a statistically significant ( p
