Nucl. Med. Biol. Vol. 19, No. 7, pp. 727-735, 1992 0883-2897/92 $5.00 + 0.

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Int. J. Radiat. Appl. Instrum. Part B Copyright 0 1992 Pergamon Press Ltd
Printed in Great Britain. All rights reserved

A Study of the Concept of Non-radioactive

Unit-dosed Reagent Kits [Cold Unit Doses
(CUDS)] as an Efficient and Cost-saving
Method for 99mTc Radiopharmaceutical
Preparation
CHINDA LERTHIRUNWONG’, KENNETH T. CHENG’* and
WILLIAM B. HLADIK III3

’ Division of Nuclear Medicine, Department of Radiology, Vajira Metropolitan Hospital, Bangkok 10300,
Thailand, 2Hospital Pharmacy Practice and Administration, Medical University of South Carolina,
171 Ashley Avenue, Charleston, SC 29425 and ‘College of Pharmacy, University of New Mexico,
Albuquerque, NM 87131, U.S.A.

(Received 4 March 1992)

Traditionally, when preparing 99mTc-labeled radiopharmaceuticals, p”Tc]pertechnetate is added to the

entire contents of a vial of reagent kit, and patient doses are subsequently withdrawn from the vial. This
technique of compounding can be potentially wasteful for two reasons: (1) once reconstituted with 99mTc,
most reagent kits have a relatively short shelf-life, and thus the entire contents may not be used before
expiration and (2) due to a need to conserve radioactivity in many hospitals, enough Pg”Tc]pertechnetate
is added to the reagent kit in order to retrieve only 1-2 patient doses, even though adequate chemicals
(ligand, reducing agent, etc.) are present in the reagent kit to supply as many as 5-10 doses. Hence, a
method for optimizing the efficient use of reagent kits would be desirable. The purpose of this study was
to determine the feasibility of unit-dosing non-radioactive reagent kits and storing these cold unit doses
(CUDS) for eventual labeling with 99mTc.To evaluate this concept, unit doses were prepared from reagent
kits of medronate (MDP) and pentetate (DTPA). The specific variables studied in this research were the
effects of storage time, storage temperature and reconstitution volume (dilution) on the unit doses. These
effects were monitored by measuring the radiochemical and biodistribution properties of the unit doses
following their final reconstitution with pmTc]pertechnetate. The labeling efficiency was determined using
instant thin layer chromatography (ITLC), and the biodistribution patterns of these radiolabeled CUDS
were studied in mice. The results showed that MDP- and DTPA-CUDS stored at - 18°C retained the
properties which resulted in acceptable radiochemical purity and biodistribution in mice for as long as
30 days. On the other hand, the radiochemical purity of MDP and DTPA unit doses stored at 25°C
deteriorated rapidly. Mean radiochemical purities as low as 0.58819.4% were observed on day 30. Altered
biodistributions were observed in a manner consistent with the decreased labeling efficiencies. The CUDS
of lower dilution (3 mL) appeared to be more stable than the CUDS of higher dilution (10 mL). However,
the effect of reconstitution volume was much less significant than the temperature effect on the CUDS.
In conclusion, the concept of unit-dosing non-radioactive reagent kits appears to provide an efficient and
cost-saving method for preparing infrequent and emergency radiopharmaceutical doses. The study also
showed that the storage temperature of these unit doses is critical to the success of the procedure. The
volume of reconstitution has a minimal impact on the stability of CUDS if stored at the appropriate
temperature.

Introduction pertechnetate and the non-radioactive (cold) reagent

Technetium-99m-labeled compounds are the most kit. The cold reagent kit contains the ligand, reducing
commonly used radiopharmaceuticals in nuclear agent and other necessary pharmaceutical excipients.
medicine. Nearly 80% of all radiopharmaceuticals The cold reagent kits are generally supplied commer-
used in nuclear medicine are pgmTc]technetium- cially by the manufacturers as multidose vials (Rob-
labeled compounds (Saha, 1984). The preparation of bins, 1984) for administration to as many as S-10
[99mTc]technetium compounds generally requires two patients. Once these reagent kits are reconstituted
components: P9mTc]technetium in the form of with p’“Tc]-pertechnetate in normal saline, they typ-
ically must be used within 6-8 h due to physical decay
of 99mT~ and inherent chemical instability of the
*Author for correspondence. labeled compounds. After the expiration time,

727
728 CHINDA LERTHIRUNWONG CI al
unacceptable amounts of radiochemical and chemical
impurities can be formed from the decomposition of
the radiolabeled compounds (Saha, 1984). Moreover,
the shelf-life of most reagent kits (following radiola-
beling) is limited to several hours due to the fact that
they contain no preservatives.
Because of the short shelf-life of the reconstituted
kit, quite often one multidose vial is used for only one
or two patients. This is particularly true in small
hospitals where there are not sufficient patient pro-
cedures on a daily basis. Even in large hospitals or
centralized nuclear pharmacies, it is possible that the
multidose vial may be used for only one patient in
certain infrequent procedures or emergency cases.
This incomplete usage of the multidose reagent kits
significantly increases the cost of the associated
nuclear medicine procedures.
In order to minimize the cost of radiopharmaceuti-
cals, a method is needed to improve the utilization of
multidose kits. This problem may be solved with
some basic pharmacy concepts. One practical way to
solve this problem is to prepare cold unit doses
(CUDS) from these multidose kits, i.e. withdraw and
store small aliquots of reagent kits prior to labeling
with 99mTc. It is possible to prepare 5-10 aliquots
(CUDS) from the multidose kit by reconstituting the
kit with normal saline (0.9% NaCI) and withdrawing
the CUDS before the addition of P9”Tc]-
pertechnetate. These reconstituted CUDS can be
stored and each one can be individually labeled
with 99mTc for a single patient use (unit dose) by
simply adding the appropriate activity and volume
of [99mTc]pertechnetate upon request. The major
obstacle to this method is that the stannous contents
in the reconstituted unit doses can be rapidly oxidized
at normal room temperature storage conditions
(Saha, 1984; McBride et al., 1979). Thus, the
success of this method will undoubtedly depend on
the use of a reliable method that can stabilize the
reconstituted CUDS before the addition of
[99mTc]pertechnetate.
Based on pharmaceutical and chemistry knowledge
(Kostenbauder, 1975; Martin et al., 1973), storage
temperature may be a very important factor that
could determine the stability of these CUDS. Tem-
perature has a significant impact on the chemical
kinetics. It is a well established fact that low tempera-
tures can stabilize most pharmaceutical preparations
and decelerate the decomposition process. Based on
the chemistry of the reagent kits, this principle may
also apply to the reconstituted cold unit doses. Thus,
the CUDS prepared from the multidose kits may be
stabilized at an optimal low temperature for a reason-
able time period (from days to months) until they are
used. In addition to the temperature effect, the vol-
ume of saline used to reconstitute the cold multidose
kit may also affect the final labeling efficiency. Studies
have shown that the dilution factor, which determines
the final tin concentration and the ligand-to-Tc ratio,
may significantly alter the product labeling efficiency
(Merlin et al., 1973; Owenwanne et al., 1974; Majew-
ski et al., 1981). When the tin concentration is too
low, there may be a significant decrease in the labeling
efficiency of 99mT~radiopharmaceuticals.
This experiment was designed to prepare non-
radioactive unit doses from multidose kits and to
determine the effect of two reconstitution volumes,
two storage temperatures and the length of storage on
the radiochemical stability and biological behavior of
the final 99mTc-labeled unit doses. We evaluated the
radiochemical purity by determining the levels
of [99mTc]pertechnetate (TcO; ) and hydrolyzed-
reduced 99mTc (Tc-HR) in the 99”Tc-labeled unit
doses up to 30 days after preparation. Numerous
chromatographic procedures for evaluating the
radiochemical purity of 99mTc radiopharmaceuticals
are available (Merlin et al., 1973; Owenwanne et al.,
1974; Majewski et al., 1981; Colombetti et al., 1975,
1976; Eckelman and Richards, 1972; Eckelman et al.,
1971, 1972; Persson and Darte, 1974; Persson, 1975;
Darte and Persson, 1980; Gutkowski and Dworkin,
1971; Billinghurst, 1973; Shen et al., 1974; Zimmer
and Pavel, 1977a,b, 1978; Zimmer et al., 1982; Loberg
et al., 1976; Fritzberg and Huckafy, 1979). The
present study employed the standard instant thin
layer chromatography system (ITLC) to determine
the radiochemical purity of unit doses prepared from
two very common radiopharmaceuticals, medronate
(MDP) and pentetate (DTPA). In addition, the
biodistribution of these radiolabeled unit doses (in
major organs) was studied in mice.
Materials and Methods
MDP bone imaging agent (MPI MDP KIT
MULTIDOSE, Medi-Physics Inc.) and DTPA renal
imaging agent (MPI DTPA KIT MULTIDOSE,
Medi-Physics Inc.) were selected for our study. One
group of unit doses was prepared using the reconsti-
tution volume of 3mL, which is within the volume
range recommended by the manufacturer. (The man-
ufacturer of these products has recommended the
reconstitution volume of p”Tc]pertechnetate in
2-8 mL to be added to each kit.) Another group of
unit doses used a reconstitution volume of IOmL,
which exceeds the recommended volume. All reagent
kits were reconstituted with 0.9% sodium chloride
solution containing no bacteriostatic agent; 0.5 mL
aliquots (unit doses) were taken from the reconsti-
tuted kits and placed in sterile IO mL vials. The unit
doses were then stored at two different temperatures:
room temperature (25°C) and freezing temperature
( - I SC).
We evaluated the effect of the following parameters
on the stability of unit doses up to 30 days: (I) the
reconstitution volume (3 vs 10 mL) and (2) the stor-
age temperature (25 vs - 18°C). Based on a prelimi-
nary experiment, the sampling times for MDP unit
doses were chosen on days 0, 7, I4 and 30 after
preparation (i.e. after unit-dosing of the reagent kits).
 Stability of non-radioactive unit-dosed kits 129

Table 2. Radiochemical impurities of

.FTC~MDP
, 3-mL CUDS stored at - 18°C
% TcO; % Tc-HR
Day 0 0.20 0.60
SD 0.02 0.30
Day 7 0.16 0.16
SD 0.05 0.12
Day 14 0.07 0.16
SD 0.04 0.15
Day 30 0.04 0.11
SD 0.3 0.04
lP < 0.05 two-tailed Dunnett test on raw data.

remained at the origin. When the Gelman ITLC-SG

Fig. 1. Flowchart of the methodology. *For DTPA the
sampling times were: days 0, 3, 7, 14 and 40. The sampling
times for MDP were: days 0, 7, 14 and 30.
The sampling times for DTPA unit doses were on
days 0, 3, 7, 14 and 30 after preparation. Day 0 was
the day of preparation and the results from this day
were used as controls. To test for reproducibility, five
unit doses of each compound were studied at each
sampling time. In all studies, 0.74GBq/O.S mL
Pg”Tc]pertechnetate was used for radiolabeling of
MDP unit doses and 0.37 GBq/O.S mL of pmTc]-
pertechnetate was used for radiolabeling of DTPA
unit doses. The overall experimental design is shown
in Fig. 1.
The chromatographic procedures used in this
reasearch were the standard methods used in nuclear
pharmacy in accordance with the recommendations
from Robbins (1984). 31ET Whatman chromatog-
raphy paper (Whatman Chromatography Products,
Clifton, N.J.) and Gelman ITLC-SG sheets (Gelman
Instruments Co., Ann Arbor, Mich.) were cut into
1.5 x 20 cm strips. Pencil lines were drawn on the
strips at points 2 and 18 cm from the bottom. For
both MDP and DTPA, the Whatman strips were
developed in acetone. With acetone as the solvent
PTclpertechnetate (TcO; ) migrated in close prox-
imity to the solvent front while the labeled com-
pounds and the hydrolyzed-reduced species (Tc-HR)
strips were developed in 0.9% NaCl, the Tc-HR
remained at the origin while both the TcO; and
labeled compounds migrated close to the solvent
front. After development, the strips were dried im-
mediately and cut into five equal pieces. The radio-
activity in each piece was counted using an
automated y-counter.
The organ distributions of the radiolabeled unit
doses were evaluated in ICR strain male mice
(25-32 g). Five mice were used for each experimental
condition. l/20 mL of the radiopharmaceutical was
injected i.v. through the tail vein. A sacrifice time of
2 h post-injection was selected for MDP and a sac-
rifice time of 10 min after injection was used for
DTPA. The blood, liver, stomach, kidneys and femur
were removed from the animal and weighed. The
activity in each organ was determined by counting in
a well scintillation counter (Tracer Analytic Model
1197, Automatic Gamma Counting System) and
compared with a standard (for decay correction). In
order to calculate the percentage of total organ
uptake, the blood activity was normalized to 7% of
the body weight and the bone activity was normalized
to 10% of the body weight. The final results were
expressed in % administered dose/organ.
Radiochemical impurities (% TcO; and % Tc-
HR) and % dose/organ were calculated and
compared to the results from day 0 (controls).
The percent of TcO; was calculated from the
31ET-acetone system and percent of Tc-HR was
calculated from the ITLC-SG-normal saline system.
The final results were obtained from the following
equations:
% [99mTc]pertechnetate (%TcO; )

Table 1. Radiochemical impurities of

counts at the solvent front
= x 100
phTc]MDP unit doses (3-mL reconstitution total counts
volume) stored at 25°C
% TcO; % Tc-HR
% hydrolyzed-reduced [99mT~](Tc-HR)
Day 0 0.20 0.60
SD 0.02 0.30 counts at the origin
Day 7 22.05’ 0.60 = x 100
SD 41.02 0.88 total counts
Day 14 39.92, 0.28
SD 51.20 0.62
Day 30 19.52. I .08 % radiochemical purity
SD 41.86 1.71
lP < 0.05 two-tailed Dunnett test. = 100% - [(% TcO;) + (% Tc-HR)].
730 CHlNDA ~ERTHIRUNWONG et al

Table 3. Radiochemical impurities of

[99mTc]MDP unit doses (IO-mL reconstitution
volume) stored at 25’C
% I-co; % Tc-HR
Day 0 0.16 0.62
SD 0.05 0.62
Day 7 1.91 1.60
SD 13.36 I .68
Day I4 95.01; 0.50
SD 9.91 0.82
Day 30 99.23’ 0.02
SD 0.14 0.01
*P < 0.05 two-tailed Dunnett test.

0 7 14 30
DRY
Fig. 2. Major organ uptakes of [WmTc]MDPunit doses
(prepared from 3-mL reconstituted multidose kits) stored at
25°C. *P < 0.05 two-tailed Dunnett test.
The results at each time point were statistically
compared to the control group. The ANOVA
Dunnett test (P < 0.05, two tailed) was used.
Results
Tables 1 and 2 and Figs 2, 3, 10 and 11 show the
results of the radiochemical evaluation and organ
distribution of P9mT~]MDP using unit doses with-
drawn from 3-mL reconstituted multidose kits. The
temperature effect on the MDP unit doses was clearly
demonstrated. The mean TcO; level of MDP unit
doses stored at 25°C increased from 0.20% on day 0
to 22.05% on day I. This increased to 79.52% on day
30 and was statistically different from that of day 0.
Those stored at - 18°C had less than 0.5% TcO; on
day 0 and remained relatively unchanged up to 30
days. The mean Tc-HR levels of MDP-CUDS from
both storage conditions remained at less than 2%
throughout the 30 days and no significant differences
were observed among days 0, 7, 14 and 30. The
highest mean Tc-HR level of 1.08 was observed on
day 30 for MDP-CUDS stored at 25°C.
As seen in Fig. 2, the biodistribution patterns of the
radiolabeled MDP unit doses (stored at 25°C)
showed a steady increased uptake of radioactivity in
the stomach from day 0 to day 30. This could be
explained by the presence of a high percent of TcO,
(Table 1). In addition, as TcO, levels rose, bone
(target organ) uptake of the radiolabeled MDP de-
creased whereas radioactivity levels in the blood and
liver increased. No significant distribution changes in
the major organs were observed in the MDP-CUDS
stored at - 18°C up to 30 days. Thus, the overall
biodistribution patterns were consistent with the
radiochemical purity test results.
Tables 3 and 4 and Figs 4, 5, 12 and 13 present the
results of radiochemical evaluation and organ distri-
bution of the p9”Tc]MDP using unit doses that were
prepared from the reconstitution volume of 10 mL.
The overall results of the lo-mL MDP-CUDS
appeared to be only slightly different from those of
MDP-CUDS prepared from the 3-mL reconstitution
volume. The CUDS made from lo-mL kits and then
stored at - 18°C exhibited free TcO; levels of less
than 0.5% up to 30 days (Table 4). There was a slight
increase in % TcO; on day 30. Although this differ-
ence was significant in comparison with the result
from day 0, the mean level of 0.34% on day 30 was
still acceptable from a pharmaceutical standpoint. A
more significant difference between the 3 and IO-mL
MDP unit doses was observed when the unit doses
were stored at 25°C. The deterioration of unit doses
stored at 25°C from the IO-mL reconstitution volume
appeared to be faster than that of the CUDS from the
3-mL reconstitution volume stored at 25°C (Table 3).
The products prepared from MDP unit doses stored
at 25°C exhibited a high level (7.97%) of TcO; as
early as day 7. There was 95.01% TcO; (4.49%

Table 4. Radiochemical impurities of

p”Tc]MDP IO-mLCUDS stored at - 18°C
% TcO; % Tc-HR
Day 0 0.16 0.62
SD 0.05 0.62
Day I 0.14 0.23
SD 0.05 0.23
0 7 14 30 Day 14 0.14 1.55
SD 0.06 1.634
W Day 30 0.34. 0.94
SD 0.26 1.41
Fig. 3. Major organ uptakes of pTc]MDP 3-mL CUDS
stored at - 18°C. *P < 0.05 two-tailed Dunnett test.
 Stability of non-radioactive unit-dosed kits 731

Table 5. Radiochemical impurities of

p9”Tc]DTPA unit doses (3-mL reconstitution
volume) stored at 25°C
% TcO; % Tc-HR
Day 0 0.38 0.38
SD 0.18 0.51
Day 3 21.14’ I .70
SD 41.22 I.11
Day 7 62.21* 3.13’
SD 41.65 4.04
Day 14 98.8 1* 0.21
SD 0.16 0.12
Day 30 99.36* 0.06
SD 0.10 0.07
*P < 0.05 two-tailed Dunnett test.

0 7 14 30
Day
Fig. 4. Major organ uptakes of p”Tc]MDP unit doses
(prepared from IO-mL reconstituted multidose kits) stored
at 25°C. *P -c0.05two-tailed Dunnett test; tdata not
available.
radiochemical purity) for the lo-mL unit doses
compared to 39.92% TcO; (59.80% radiochemical
purity) for 3-mL unit doses on day 14 and 99.23%
(0.64% radiochemical purity) for the IO-mL unit
doses compared to 79.52% (19.40% radiochemical
purity) for the 3-mL unit doses on day 30. There were
correspondingly altered major organ biodistribution
patterns on days 14 and 30 (Fig. 4).
Tables 5 and 6 and Figs 6, 7, 14 and 15 show the
results of the radiochemical evaluation and organ
distribution of p9*Tc]DTPA using unit doses with-
drawn from the 3-mL reconstitution volumes. A
temperature effect was again demonstrated. A mean
TcO; level of 21.14% (77.16% radiochemical purity)
was observed on day 3 in the preparations using the
DTPA unit doses stored at 25”C, and increased to
99.36% (0.58% radiochemical purity) on day 30
(Table 5). CUDS stored at - 18°C remained at less
than 0.7% (99% labeling efficiency) up to 30 days.
The Tc-HR levels in both storage conditions re-
mained at less than 2% throughout the 30 days with
one exception (day 7). On day 7, the % Tc-HR of
DTPA unit doses stored at 25°C was significantly
higher (3.13%). The biodistribution pattern again
showed a correlation between % TcO; and % dose
concentrated in the stomach (Figs 6 and 7).
Tables 7 and 8 and Figs 8, 9, 16 and 17 summarize
the results of the radiochemical evaluation and organ
distribution of the p”Tc]DTPA using unit doses
prepared from the IO-mL reconstitution volume. In
comparing these results with those of unit doses
withdrawn from kits reconstituted with 3-ml, some
significant volume effects were observed. The overall
mean % TcO; levels from the IO-mL CUDS were all
higher than those of 3-mL CUDS (even on day 0).
The mean % TcO; (22.98%) of lo-mL CUDS at
- 18°C was much higher on day 7 than that (0.45%)
of 3-mL CUDS at the same temperature. (The results
on day 7 cannot be easily explained since the TcO;
levels returned to reasonable levels on days 14 and 30.
Possibly excessive air was introduced into the day 7
unit doses during their initial withdrawal from the
reagent kit or during radiolabeling with [99mTc]-
pertechnetate.) The mean % TcO; levels of pre-
viously-frozen CUDS on days 14 and 30 (1.96 and
1.08%, respectively) were within USP accepted limits
but they were still higher than the corresponding data
for 3-mL CUDS (0.52 and 0.64%, respectively). Cor-
respondingly higher radioactivity levels were ob-
served in the blood, liver and stomach for IO-mL
CUDS on day 7 (Figs 8 and 9). Similar to the MDP
unit dose results, the radiochemical purity of IO-mL

Table 6. Radiochemical impurities of

[99mTcc]DTPA3-mL CUDS stored at - 18°C
% TCO; % Tc-HR
Day 0 0.38 0.38
SD 0.18 0.51
Day 3 0.70 0.63
SD 0.33 0.18
Day 7 0.45 0.78
SD 0.12 0.16
0 7 14 30 Day 14 0.52 0.51
SD 0.07 0.39
DRY Day 30 0.64 0.75
SD 0.69 0.57
Fig. 5. Major organ uptakes of ph”Tc]MDP IO-mL CUDS
stored at - 18°C. *P < 0.05 two-tailed Dunnett test.
732 CHINDA LERTHIRUNWONG er ul.

Table 7 Radmchemical mlpurltles of

1 Blood [99mTc]DTPA unit doses (IO-mL reconstitutmn
l fZi Liver volume) stored at 25 ‘C
0 Stomach
b?! Kidneys % TcO, % Tc-HR

I
N=5 Day 0 0.66 I .43
SD 0.23 0.42
Day 3 85.58’ 9.85’
SD 7.01 5.24
Day 7 99.08’ 0.20
SD 0.44 0.07
Day 14 99.39’ 0.05
SD 0.07 0.03
Day 30 99.31’ 0.04
SD 0.08 0.04
lf < 0.05 two-tailed Dunn&t test on raw data.

to at least 30 days. Although we did not study storage

0 3 7 14 30
Day
Fig. 6. Major organ uptakes of [99mTc]DTPA unit doses
(prepared from 3-mL reconstituted multidose kits) stored at
25°C. *P < 0.05two-tailed Dunnett test.
DTPA-unit doses at 25°C deteriorated at a much
faster rate than those of 3-mL unit doses. On day 3,
the radiochemical purity of IO-mL unit doses had
already decreased to 4.57% (85.58% TcO;) com-
pared with 77.16% (21.14% TcO;) of 3-mL unit
doses.
Discussion
In this study, ITLC and biodistribution studies
were used to determine if CUDS stored at an appro-
priate temperature following withdrawal from vials
of non-radioactive reagent kits (to which an appro-
priate reconstitution volume was added) could pro-
duce acceptable (stable) radiopharmaceuticals upon
the eventual addition of p”‘Tc]pertechnetate. At least
for MDP and DTPA, 0.5 mL CUDS can be prepared
using 3 mL as the reconstitution volume and - 18°C
as the storage temperature. These CUDS are stable up
15
times longer than 30 days, it is possible that the
storage time can be further prolonged.
In evaluating the temperature and dilution effects
on the stability of CUDS, it appears that temperature
is a major determinant for stabilizing the CUDS. This
observation agrees with common pharmaceutical
knowledge. This effect is probably due to the stabiliz-
ing effect of cold temperature on the stannous con-
tents of CUDS. The stannous contents of unit doses
stored at room temperature can be rapidly oxidized
if exposed to air. This may explain the poor labeling
efficiency of unit doses stored at room temperature.
The volume of saline used to reconstitute the cold
reagent kit appears to have some, but much less
significant, effect on the stability of CUDS. The
radiochemical purity of DTPA unit doses prepared
from the larger reconstitution volume (10 mL) group
was lower and more fluctuating than that of the
smaller reconstitution volume (3 mL) group.
Overall, the MDP unit doses showed a better and
more consistent radiochemical purity than the DTPA
unit doses. This may be related to the ascorbic acid
which is incorporated into the MDP kit as an anti-
oxidant agent. Results are generally consistent with
studies that have shown that the presence of oxidants
and oxygen has a greater adverse effect on the
stability of radiopharmaceuticals containing low con-
centrations of stannous ion (Merlin et al., 1973;
Owenwanne et al., 1974; Majewski et al., 1981) than
those with higher stannous concentrations.
The present economic climate has forced medical
professionals to realize the importance of the concept

Table 8. Radiochemical impurities of

[~~~T~]DTPA IO-mLCUDS stored at - 18°C
% TcO; % Tc-HR
Day 0 0.66 I .43
SD 0.23 0.42
Day 3 I .25 I .I8
SD 0.78 I .32
Day I 22.98’ 7.54’
SD 28.16 10.88
3 7 Day I4 I .96 1.63
SD 0.66 0.58
Day Day 30 I .08 1.10
Fig. 7. Major organ uptakes of [WmTc]DTPA 3-mL CUDS SD 0.35 0.61
stored at - 18°C. lP < 0.05 two-tailed Dunnett test.
 Stability of non-radioactive unit-dosed kits 133

25 _ u Blood 100
N=S
q Liver
90

20. a0
I

2 p TO-
5 15.
B
1
u
:I_
$j 10. a 40-
z 30 -
5.
5. 20
10
1
0 . . . . . . . . . . . . . . . 0: t
. . . .
0 3 7 14 30 0 7 14 30
Day

Fig. 8. Major organ uptakes of [99mTc]DTPA unit doses Fig. IO. Radiochemical purity of pTc]MDP unit doses
(prepared from IO-mL reconstituted multidose kits) stored (3-mL reconstitution volume) stored at 25°C. *P -c 0.05
at 25°C. *P < 0.05 two-tailed Dunnett test. two-tailed Dunnett test.

of cost-effectiveness. Nuclear medicine is similarly
affected by the skyrocketing health costs in this
nation and throughout the world. One of the
major hindrances preventing a more widespread util-
ization of nuclear medicine procedures is the cost of
radiopharmaceuticals. The fact that most non-radio-
active reagent kits are available only in multi-dose
forms adds an additional cost to nuclear medicine
facilities that frequently cannot fully utilize the
entire reconstituted multidose reagent kit before the
time of expiry. This study has shown that the concept
of unit dosing cold reagent kits could be a solution
to this problem.
In conclusion, this study has shown that cold
unit doses (CUDS) of MDP and DTPA can be
easily prepared by reconstituting a commercial multi-
dose reagent kit with non-bacteriostatic normal
saline, withdrawing aliquots of this solution and
then freezing (- 18C) these aliquots for future use
up to 30 days. Although the results suggest that
the reconstitution volume is not a significant factor
for MDP- and DTPA-CUDS stored at - 18°C it
may still be an important consideration in the
preparation of some other radiopharmaceutical
CUDS. The preparation of CUDS from other 99mTc
radiopharmaceutical reagent kits may require
additional studies as different 99”Tc-1abe1ed com-
pounds have different chemical properties. Finally,
the concept of preparing CUDS from reagent kits
appears to be an efficient and practical method to
increase the cost-effectiveness of using selected *Tc
radiopharmaceuticals. Since this preparation departs
from the instructions in the package insert, pro-
fessional judgement should be exercised to ensure
that one is in full compliance with state and federal
regulations. The NRC allows licensees to depart
from the manufacturer’s instructions for the prep-
aration of reagent kits providing the licensees meet
certain conditions and limitations (Federal Register,
1990).

15 100 n n

QO N-5
1
50

b 70
g 50
Q
B 50
c 40
ap 30
20
10
0 r- I I

0 7 14 30
0 3 14 30
Day
Fig. 9. Major organ uptakes of p”Tc]DTPA IO-mL CUDS Fig. 11. Radiochemical purity of [99”Tc]MDP 3-mL CUDS
stored at - 18°C. *P < 0.05 two-tailed Dunnett test. stored at -18°C.
734 CHINDALERTHIRUNWONG
et al.

8’ q 8

N=5

10 -

Of t
0 7 14 30 037 14 30
Day Day
Fig. 12. Radiochemical purity of [““Tc]MDP unit doses Fig. 15. Radiochemical purity of p”Tc]DTPA 3-mL CUDS
(IO-mL reconstitution volume) stored at 25°C. *P < 0.05 stored at - 18°C.
two-tailed Dunnett test.

100 loo-
N=!i
90 90-
N=S
60 60-
I--
& 7Q-
z
H 60- I 60-

- - 60-

a 4O-
60- E 40-

* 30- a9 30-

20 - if 70-
m-:
10 -

o! ,
0 7 14 30 0 6 10 16 30
Day Day
Fig. 13. Radiochemical purity of pmTc]MDP IO-mL CUDS Fig. 16. Radiochemical purity of ~TcJDTPA unit doses
stored at - 18°C. (IO-mL reconstitution volume) stored at 25°C. *P < 0.05
two-tailed Dunnett test.

1007 N=5 lOO-

90- 90-

60- 60-

E 70.
Ii 60

- 60-

E 40.
* 30'

20-

lo-
*
0: 1

037 14 30 037 30
Day &
Fig. 14. Radiochemical purity of p9”Tc]DTPA unit doses Fig. 17. Radiochemical purity of pmTc]DTPA IO-mL
(3-mL reconstitution volume) stored at 25°C. *P < 0.05 CUDS stored at - 18°C. *P < 0.05two-tailed Dunnett
two-tailed Dunnett test, test.
 Stability of non-radioactive
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