Applied Radiation and Isotopes 59 (2003) 383–387

ARTICLE IN PRESS

*Correspond

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doi:10.1016/j.ap

Comparisons of activity measurements withradionuclide calibrators

P. Oropesaa,*, A.T. Hern!andeza, R. Serraa, E. Mart!ıneza, C. Varelab

aCentro de Is !otopos (CENTIS), P.O. Box 3415, San Jos!e de las Lajas, Havana, CubabCentro de Control Estatal de Equipos M!edicos (CCEEM), Calle 4, No 455 (altos), Vedado CP 10400, Havana, Cuba

Received 4 August 2003; received in revised form 2 September 2003; accepted 3 September 2003

Abstract

The correct administration to a patient of the prescribed activity of a radiopharmaceutical is an important factor to

ensure the confidence in the diagnosis or the therapeutic efficiency, while at the same time keeping the unnecessary

human exposure as low as possible.

Comparisons of activity measurements for 131I, 201Tl and 99mTc with radionuclide calibrators were organized the first

time in Cuba during 2002 with the aim of obtaining information about the quality of administration of

radiopharmaceuticals. Ten Cuban nuclear medicine departments and the laboratories involved in the production of

these kinds of compounds participated in the comparison runs. The results presented in this paper facilitated the

identification of several problems and initiated corrective actions. In addition, they indicate the necessity of establishing

Quality Systems in nuclear medicine in Cuba.

r 2003 Elsevier Ltd. All rights reserved.

Keywords: Radionuclide calibrator; Activimeter; Comparison; Activity measurements; Nuclear medicine

1. Introduction

Before a radiopharmaceutical is administered to a

patient, its activity should be determined on the basis of a

measurement. The correct administration to a patient of

the prescribed activity is an important factor to ensure the

confidence in the diagnosis or the therapeutic efficiency,

while also keeping unnecessary human exposure as low as

possible. In the case of children subjected to a diagnostic

procedure or who undergo therapy with radionuclides, the

administration of well-know activities is of the utmost

importance. That is why regulations and limiting values

for the uncertainties of activity measurements have been

prescribed (European Pharmacopoeia, 1982; Gu!ıa, 2002).

An upper limit of 10% has been established for the

expanded uncertainty of the activity value, with a

coverage factor, k; equal to 3. Larger uncertainties on

ing author.

ess: poropesa@centis.edu.cu (P. Oropesa).

e front matter r 2003 Elsevier Ltd. All rights reserve

radiso.2003.09.001

these administrations may lead to overdoses or under-

doses, both undesirable due to their high risk-to benefit

ratio, or their risk without any benefits, respectively. In

addition, they could make the comparability of the results

obtained in various hospitals questionable.

During 2002, the Radionuclide Metrology Depart-

ment of the Isotope Center (CENTIS-DMR) has

organized several comparisons with various radio-

nuclides in order to obtain information on the quality

of the activity measurements during production and

administration of radiopharmaceuticals in Cuba. The

participants were expected to measure radioactive

solutions in glass vials and in syringes, to simulate the

administration of a radiopharmaceutical to a patient,

and to report on their instrument measurement and

administration procedures. The comparisons results,

shown in this paper, have uncovered several problems

and initiated corrective actions. Moreover, they reflect

the necessity of establishing Quality Systems in nuclear

medicine in Cuba.

d.

ARTICLE IN PRESSP. Oropesa et al. / Applied Radiation and Isotopes 59 (2003) 383–387384

2. Comparisons

Comparisons focussed on providing information on

the performance of the Nuclear Medicine departments

and the two laboratories involved in the production of

radiopharmaceuticals in Cuba, measuring the activity

of 131I, 201Tl and 99mTc with radionuclide calibrators.

The aim of the comparisons was to contribute to the

improvement of the quality of the measurements made

in the country with that type of instrument. Particularly,

these exercises checked not only the instruments, but

also the procedures used in the routine determinations

and the performance of the personnel involved in the

measurements.

The programme used for the comparisons was the

known-value scheme (ISO/IEC, 1997). The radioactive

samples with a known radionuclide activity were sent to

the participants. The samples sent to a participant were

measured only by that participant. Therefore, it is

possible to evaluate the capability of an individual

laboratory to measure the activity of the sample and to

provide numerical results for comparison with the value

assigned at CENTIS-DMR.

Glass vials and 5ml capacity plastic syringes of the

type routinely used in nuclear medicine were filled with

single nuclide solutions (the glass vials containing 5ml

and the syringes containing approximately 2.5ml of the

radioactive solution). The reference activity of each

individual sample was established as the resulting value

of its measurements in an activimeter, that had been

previously calibrated at CENTIS-DMR for the specific

nuclides and sample geometries. The reference sources

for the calibration of this activimeter were prepared in

appropriate geometries by weighing aliquots from

solutions calibrated using a germanium spectrometer.

For each radionuclide of interest, the gamma-spectro-

metry determination of the activity concentration of the

solution, is carried out with n (usually eight–ten) point

sources prepared by weighing 20/50-mg drops, with the

mass of each drop being determined by the pychnometer

method (Oropesa et al., 2002). Traceability to SI units is

guaranteed by using point gamma sources certified by

the Hungarian National Office of Measures (OMH) for

the efficiency calibration of the germanium spectro-

meter. Finally, the activity measurements of the

activimeter are traced with a relative combined standard

uncertainty of 2% to the calibrated gamma spectro-

meter. All 131I and 201Tl comparison samples were also

measured in this activimeter at CENTIS-DMR after

they were received back from the participants. This type

of check was not possible for the 99mTc samples because

of the short half-life of that nuclide. As a conclusion of

these controls and the results of previous stability

studies (Oropesa et al., 2002), all samples used for the

comparisons were considered stable enough for the

evaluation of the participant’s performance.

Ten Cuban nuclear medicine departments and the two

laboratories involved in the production of radiophar-

maceuticals participated in the comparisons. They were

asked to apply their established routine procedures for

measurements in the radionuclide calibrator and for the

activity administration to the patient. The selection of

the geometries and nuclides to be sent to a particular

participant was done in correspondence with the ones

used in routine activity measurements at the respective

institution. Specifically, samples in a glass vial geometry

were distributed only to the two laboratories involved in

the production of radiopharmaceuticals. The nuclear

medicine departments were provided with 3 radioactive

samples of each nuclide used by them, two of these

samples in the glass vial geometry and another one in the

syringe geometry. All participants were asked to

determine the activity in the received vials and syringes.

Supplementary information was requested about the

instrument and measuring procedures used.

Table 1 summarizes the results of the comparisons for

the determination of the activity of 131I, 201Tl and 99mTc

in the glass vials and syringes. Xmed and Xref are the

activity values (related to the same reference date)

reported by the participants and measured at CENTIS-

DMR, respectively. As had been expected, the results for

the vials and syringes are in good agreement, as the

attenuation of the radiation at a photon energies of 140

and 364 keV depends only slightly on the materials and

thickness of the sources and their containers (Debertin

and Schrader, 1992). In the 131I and 201Tl comparisons,

80% or more of the participants obtained results that

agreed within about 10% with the value measured at

CENTIS-DMR and thus their performance can be

evaluated as satisfactory. Particularly, only two nuclear

medicine laboratories, one during the 131I comparison,

and another during the 201Tl comparison reported

unsatisfactory results. The unsatisfactory performance

of these two laboratories was caused by the same error:

the wrong choice of the switch-selectable radionuclide

option during the sample measurements. There were no

available written procedures for any of the radionuclide

calibrator measurements at either of these two labora-

tories.

During the 99mTc comparison, 100% of the partici-

pating laboratories reported results that agreed to within

10% of the value measured at CENTIS-DMR for both

glass vial and syringe. This comparison was organized at

the end of 2002, after the results of the previous two

comparisons (131I and 201Tl) had been discussed with the

participants.

Thirteen radionuclide calibrators from 5 different

manufactures were used during comparisons, one of

which predominated (see Table 2). The comparison

results demonstrated that the calibration condition of

all of the calibrators used was satisfactory. Here is

necessary to point out that, at the beginning of the 2002

ARTICLE IN PRESS

Table 2

Manufacturers of the radionuclide calibrators used during

comparisons

Manufacturer No. of instruments

PTW–Freiburg 8

Biodex Medical Systems 2

Victoreen 1

Alfanuclear 1

Capintec 1

Table 1

Results of the comparisons for the determination of the activity of 131I, 201Tl and 99mTc in the glass vials and syringes

Nuclide 131I 201Tl 99mTc

No. of participants 9 5 9

Percentage of participants reporting satisfactory results 88.9% 80% 100%

1. Glass vials

No. of reported values 17 8 18

Percentage of results with Xmed � Xrefj j=0:033Xref p3 88.2% 75% 100%

2. Syringes

No. of reported values 5 3 8

Percentage of results with Xmed � Xrefj j=0:033Xref p3 100% 66.7% 100%

Xmed-activity reported by the participant; Xref-activity measured at CENTIS-DMR.

Table 3

Observed differences between the installed by the producer, Ai ;and the determined by the CENTIS-DMR, Ai0; calibrationcoefficients for the PTW-Freiburg’s instruments, under the

specific conditions used in the laboratories

Nuclide Source

geometry

No. of

results

Mean of

Ai=Ai0

Standard

deviation

131I Glass vial 6 0.968 0.003

Syringe 7 0.984 0.009

201Tl Glass vial 6 0.879 0.007

Syringe 6 0.879 0.007

99mTc Glass vial 7 0.912 0.002

Syringe 6 0.892 0.007

P. Oropesa et al. / Applied Radiation and Isotopes 59 (2003) 383–387 385

all instruments were calibrated by the CENTIS-DMR

for the nuclides and geometries used in their routine

activity measurements. During these calibrations per-

formed under the specific conditions used in the nuclear

medicine departments, as can be seen from Table 3,

cases of significant differences were found between the

calibration coefficients installed by the producer, Ai; andthose determined by the CENTIS-DMR, Ai0; for PTW-

Freiburg instruments. A lead shield was used for the

reference calibration in the manufacture and the

chamber is employed without any optional shield in all

eight laboratories with this type of chamber. Therefore,

the significantly low amount of backscatter could

explain the obtained less than 1 values for the quotient

Ai=Ai0: Although this fact was noted and an approxi-mated correction factor equal to 1.1 applied to the

‘‘without shield measurements’’ specified in the instru-

ment manual, very often the activity value shown by the

instrument was used without any correction during the

administration of the pharmaceutical to the patient in

the hospital. The new Ai0 calibration coefficients,

determined for the specific conditions of use, were

installed in the eight PTW-Freiburg instruments. For the

instruments of the other four manufacturers, no

significant differences, in compliance with the IEC

1145 standard (IEC, 1992), were found between the

installed by the producer and the determined by

the CENTIS-DMR calibration coefficients, under

the specific conditions used in the nuclear medicine

departments.

The nuclear medicine laboratories were additionally

requested to simulate the administration to a patient by

injection, of a prescribed activity. Sealed glass vials,

containing a non-radioactive solution with a chemical

composition similar to the composition of the compar-

ison samples of each employed nuclide, were also sent to

the participants for this administration test. These vials

simulated the patient to whom the activity should be

administered and the non-radioactive solution contained

inner the vials played the role of the blood for carrying

out the typical ‘washing’ or ‘rinsing’ of the syringe

during the injection of the radiopharmaceutical. For this

test, the activity to be ‘‘administered’’ must be taken

with a syringe of a type commonly used by the

participants, from one of the received comparison

samples in the glass vial geometry and injected through

ARTICLE IN PRESSP. Oropesa et al. / Applied Radiation and Isotopes 59 (2003) 383–387386

the rubber stopper to the vial with the non-radioactive

solution. The participants were asked to report:

* the prescribed activity value to be administered,

Xplan,* the activity in the original vial, Xini,* measurement result of the activity taken in the

syringe, Xsyr,* measurement result of the ‘‘true’’ administered

activity, transferred to the sealed glass vial with the

non-radioactive solution from the syringe, Xadm,* residual activity in the original vial,* activity of the radioactive wastes generated during

this process, and* supplementary information about the administration

procedure employed.

The sum of the Xsyr plus the residual activity in the

original vial was always statistically the same as the Xinivalue; that is, no activity losses were detected during the

test. The z-core statistic

z ¼ Xadm � Xplan

��

��=0:033Xplan

was calculated to evaluate the performance. The results

of this simulated administration study are presented

in Table 4 and Fig. 1. Only 47% of the reported

‘administered’ activity results, Xadm, agreed to within

10% of the intended value, Xplan. Two of the results with

Table 4

Results of the simulated administration test

No. of participants 8

Percentage of satisfactory results,

Xadm � Xplan

��

��=0:033Xplan p3

47%

No. of reported values 15

No. of results with Xadm � Xplan

��

��=0:033Xplan p3 7

No. of results with Xadm � Xplan

��

��=0:033Xplan p6 12

No. of results with Xadm � Xplan

��

��=0:033Xplan > 6 3

-12.00

-9.00

-6.00

-3.00

0.00

3.00

6.00

9.00

12.00

Z-s

core

z-scor

Fig. 1. Individual z-score values for the administration test.

the z-score value greater than 6 are in correspondence

with the above-mentioned measurements using the

wrong choice of the switch-selectable radionuclide

option.

These results demonstrate that the administration to

the patient of the exact planned activity should be

considered to be a problem to resolve. In particular, a

written procedure for administration of the radio-

pharmaceutical does not exist in most of the nuclear

medicine departments and in some cases when it does

exist, it is not fully available for routine work. The

criteria for acceptance of an activity measurement

during the administration process were not clearly

stated in any of the existing procedures.

3. Summary and conclusions

In the present study, an attempt has been made to

ascertain the quality of activity measurements in the

field of nuclear medicine in Cuba. When the value of

10% required in the Pharmacopoeia is used as a limit for

the uncertainty (corresponding to about three standard

deviations) of the measurement, the following conclu-

sions could be made based on these findings:

* In most nuclear medicine laboratories, the accuracy

of the activity measurements with radionuclide

calibrators suffices for 131I, 99mTc and 201Tl radio-

pharmaceuticals. Nevertheless, the deviations de-

tected in individual cases show that the possibility

of the occurrence of spurious errors is present.

Consequently, the necessary preventive actions

should be taken to reduce these types of errors to

the minimum.* The calibration of the instruments under the specific

measurement conditions used in the nuclear medicine

laboratories is an important prerequisite to guarantee

the adequate quality of the measurements results.

Otherwise, the influences of the measuring geometry

e |z|=3

The 15th result (z ¼ �28) is not shown in the figure.

ARTICLE IN PRESSP. Oropesa et al. / Applied Radiation and Isotopes 59 (2003) 383–387 387

and the type and form of the source on the

measurand are often not taken into account by these

laboratories.* It is estimated from the responses received from the

questionnaires and the discussion of the results with

the participants, that written procedures for radio-

nuclide calibrator measurements and the administra-

tion of the radiopharmaceuticals do not exist in most

of the nuclear medicine laboratories and in some

cases when they exist, they are not available for the

routine work. The criteria for the acceptance of an

activity measurement during the administration

process were not clearly stated in any of the existing

procedures.* It is estimated from the responses received from the

questionnaires that in most of the nuclear medicine

laboratories, the test measurements recommended

for the radionuclide calibrators are often not carried

out at all or only at irregular intervals.* The administration of the accurate prescribed activity

is still a problem to be resolved for improving the

quality of service to the patient in the nuclear

medicine laboratories. The adequate qualification of

the technicians in this area is of the highest

importance for this purpose.

To improve the quality of the measurements, compar-

isons with the most important nuclides should be

organized at regular intervals. These comparisons have

to be used as an important tool for the identification of

the problems and to initiate corrective actions. The

interest in this kind of comparisons should be awakened

in all laboratories working in the field of nuclear medicine.

The obtained results reflect the necessity of establish-

ing Quality Systems in the Cuban Nuclear Medicine.

Acknowledgements

We thank all analysts and participating institutions

for their collaboration during the execution of this

study.

References

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Ministerio de Ciencia, Tecnolog!ıa y Medioambiente.

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