[ DOI: 10.18869/acadpub.ijrr.14.2.99 ]
Volume 14, No 2
International Journal of Radiation Research, April 2016
Bone marrow radiation dosimetry of high dose 131I
treatment in differentiated thyroid carcinoma patients
Y. Parlak1, M. Demir2*, I. Cavdar3, S. Ereees4, G. Gumuser5, B. Uysal6,
G. Capa Kaya6, M. Koç6, E. Sayit4
1DepartmentofNuclearMedicine,MedicalFaculty,CelalBayarUniversity,BozkoyCampus,45030,Manisa,Turkey
2DepartmentofNuclearMedicine,CerrahpasaMedicalFaculty,IstanbulUniversity,Cerrahpasa,Istanbul,Turkey
3DepartmentofNuclearPhysics,ScienceFaculty,IstanbulUniversity,Istanbul,Turkey
4DepartmentofNuclearPhysics,ScienceFaculty,CelalBayarUniversity,45140,Manisa,Turkey
5DepartmentofNuclearMedicine,MedicalFaculty,CelalBayarUniversity,45030,Manisa,Turkey
Downloaded from ijrr.com at 10:59 +0430 on Sunday June 18th 2017
6DepartmentofNuclearMedicine,MedicalFaculty,DokuzEylulUniversity,35340,İzmir,Turkey
ABSTRACT
►
Original article
*Correspondingauthor:
Dr.MustafaDemir,
Fax:+902121413106
E-mail:[email protected]
Revised: June 2015
Accepted: July 2015
Int. J. Radiat. Res., April 2016;
14(2): 99-104
DOI: 10.18869/acadpub.ijrr.14.2.99
Background: Radia on absorbed dose to the red bone marrow, a cri cal
organ in the therapy of thyroid carcinoma, is generally kept below 2 Gy for
non-myeloabla ve therapies. The aim of this study was to calculate bone
marrow radia on dose by using MIRDOSE3 package program and to op mize
the safe limit of ac vity to be administered to the thyroid cancer pa ents.
Materials and Methods: In this study, 83 thyroid cancer pa ents were
divided into 3 groups based on the amount of ac vity administered into the
body. In the groups, 3700 MBq, 5550 MBq and 7400 MBq ac vi es were used
respec vely. The curves of me-ac vity were drawn from blood samples
counts and effec ve half-life and residence me were calculated. Correla ons
of bone marrow radia on dose and radioiodine effec ve half-life were
determined as a func on of administered ac vity via ANOVA test. Tg levels
and tumour diameters were compared using Spearman’s correla on. Results:
The effec ve half-lives of 131I for three groups of whole-body, receiving 3700
MBq, 5550 MBq and 7400 MBq were calculated as 20.57±5.4, 17.8±5.8 and
18.7±3.9 hours, respec vely. The average bone marrow doses for 3 groups of
pa ents were 0.32±0.08 Gy, 0.42±0.14 Gy and 0.60±0.24 Gy, respec vely.
Conclusion: It was concluded that, the bone marrow dose to the pa ents s ll
remains within the recommended level even a9er administering an ac vity of
7400 MBq of 131I to the pa ents.
Keywords: Radioiodine treatm ent, bone m arrow dosimetry, M I R DOSE3,
thyroid cancer.
INTRODUCTION
Treatment of differentiated thyroid cancer
(DTC) with radioiodine is a standard procedure
for the ablation of remnant thyroid tissue
following surgery and for the treatment of
iodine-avid metastases (1).
The activity to be used for 131I therapy still
remains subject of discussion. Usually, patients
are treated with $ixed or standardized activities
re$lecting the physician’s rating of the most safe
or ‘adequate’ dosage rather than with an
optimized treatment activity based on prior
measurement of the patient’s individual
biokinetics (2). The target dose is the
determinant for successful therapy, and the
decisive parameters are the therapeutic activity
and the retention of 131I in the target volume (3).
There is a broad range of $ixed activities of 131I
recommended to be administered. In many
cases, an activity between 1.1 and 3.7 GBq is
prescribed for the radioiodine therapy after
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[ DOI: 10.18869/acadpub.ijrr.14.2.99 ]
Parlak et al. / Bone marrow radiation dosimetry 131I …
thyroidectomy (3,4).Higheractivity 131Iaregiven
ofsourceorgans,Os,andtargetorgansOt,bythe
insubsequenttherapiesorincaseofmetastatic
followingrelationship(14).
(2,4,5)
disease
.
The bone marrow dosimetry is used toS(Ot←Os)=Σφ(Ot←Os)Δ/m
predict the level of toxicity from radionuclide
therapy thus allowing one to deliver the most
The total dose to the target organ due to
ef$icienttherapywithaminimallevelofadverse
radioactivity in the source organ is equal to the
effects for patients. Bone marrow is one of the
product of S and cumulative activity, AD .
most radiosensitive tissues in the body and
Cumulativeactivity,AD ,istheareaunderthetimewithout stem cell support; it is commonly the
activitycurve.Theresidencetime(τ)isthearea
dose-limiting tissue for radionuclide therapy.
under a source organ's time-activity curve
The bone marrow dose limited approach was
divided by the administered activity if τ is the
originally described by Song and Sgouros (6,7).
residence time and A0 is the initial activity
This concept basically aims to guarantee the
administered to the patient, then the $inal
equationforthedose,D,tothetargetorganis
safetyoftreatment.Blood,asasurrogateofthe
organ at risk the red bone marrow, was
consideredasthecriticalorganinthisapproach.
D(Ot←Os)=AD S(Ot←Os)=A0τS(Ot←Os)
In order to avoid a serious myelotoxicity,
athresholdvaluefortheabsorbeddoseinblood
The objective of the study, was to calculate
isconsideredas2Gy(2,8,9).
bone marrow radiation dose in by using
Tocalculatethebonemarrowabsorbeddose,
MIRDOSE3packageprogramandtooptimizethe
safe limit of activity to be administered to the
the maximum tolerated activity for an
individual, an understanding of the
non-metastatic differentiated thyroid carcinoma
pharmacokinetics of the radioiodine (131I) ispatients.
necessary(10).
According to MIRD (Medical Internal
Radiation Dose) principle, calculation of the
MATERIALS AND METHODS
radiation absorbed dose for a target organ is
basedonthedistributionofradioactivematerial
Patientgroups
(radioisotope) in a single or multiple source
In this study, 83 thyroid cancer patients were
organorsystem(11,12).
divided
into 3 groups based on the amount of
A computer package program MIRDOSE3,
administeredactivity(table1).Inthe$irstgroup,
which has been developed by the MIRD
there were 48 non metastatic thyroid cancer
committee(RadiationInternalDoseInformation
patients(14male,34femalewithagerangefrom
Center, Oak Ridge Institute of Science and
22 to 79 year) that was received 3700 MBq.
education),USAisusedinthisstudyasawidely
There were 18 patients with lymph node
approved standard for internal dosimetry
(13)
metastases (3 male, 15 female with age range
method .Inthismethod,thegeometryofthe
from28to67year)inthesecondgroupthatwas
source and target organs and the attenuation
received 5550 MBq. In the third group, there
properties of the tissues in the body are
were 17 patients with distal metastases lung,
presumed on the radionuclide and its various
bone or other organ metastases (5 male, 12
decaypathways.
female with age range from 23 to 71 year)
Thefractionofradiationenergyemittedfrom
treatedby7400MBq.
the source organ that is deposited in the target
Theexperimentaldesignofthepresentstudy
organ called absorbed fraction, φ, with paired
was
previously approved by the local ethics
arguments,target-source.Thespeci$icabsorbed
committee and written informed consent from
fraction,Φ,isde$inedasφ,dividedbythemass
allpatientswasobtained.
(m)ofthetargetorgan.Shasbeenevaluatedfor
All patients in the study had previously
eachradionuclideofinterestforalargenumber
Int. J. Radiat. Res., Vol. 14 No. 2, April 2016
100
[ DOI: 10.18869/acadpub.ijrr.14.2.99 ]
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Parlak et al. / Bone marrow radiation dosimetry 131I …
(Capintec CRC 25). The resultant data’s were
used to generate time-activity curves for blood
activity.Thecurvesoftime-activityweredrawn
Groups
Administered
Number of
Mean Age
frombloodsamplescountsandeffectivehalf-life
Ac vity (MBq)
Pa ents
andresidencetimewerecalculated.
48 (14 male,
MIRDOSE3requiresthreedataasinput:(1)a
3700
50.8±12
1
34 female)
radionuclide,(2)aphantomspeci$icationand(3)
18 (3 male,
some source and target organs with
5550
41.1±10
2
15 female)
associated residence time. In the present study,
131I and adult female non-pregnant phantom
17 (5 male,
7400
53.0±16
3
12 female)
were selected in the input form. Finally, all the
values were transferred to Microsot Excel for
83
49.8±12
Total
furthercalculation.
Correlations of bone marrow radiation dose
undergone a total thyroidectomy for papillary
and
radioiodine effective half-life were
or follicular variant thyroid cancer andthyroid
determined
hormone replacement therapy had been as a function of administered
activity via ANOVA test. Study data were
discontinued for appropriate periods to assure
analysed using the SPSS software version 11.0.
adequate hypothyroidism when the 131I was
Thelevelofsigni$icancewassetatbelow0.05.
administered. The patients were without
Table 1. The age and gender of all pa ents versus
administered ac vity.
documented kidney disease or other medical
conditions that would lower normal urinary
RESULTS
excretion.
Inallpatients,theTSHlevelswereincreased
Bonemarrowdosimetry
to over 40 mIU/L after the interruption of
In the standart MIRD approach, the general
thyroid hormone replacement. Effective half-life
expressionforRM(RedMarrow)absorbeddose
(15),
of 131I in patients receiving 3700, 5550 and
is
7400MBq were calculated as 20.57±5.4,
DRM=AD RMxS(RM←RM)+ΣAD hxS(RM←h)+AD RBxS
17.75±5.8and18.70±3.9hours,respectively.The
(RM←RB)
average effective half-life for all three groups
Where DRM is the mean absorbed dose in RM.
wascalculatedas19.00±5.0hours.Bonemarrow
AD RM, AD h, AD RB are cumulated radioactivity in red
doses for patients receiving 3700, 5550 and
marrow (RM), other organ source (h) and the
7400MBq administered activities were found to
reminder of body (RB), respectively. S(RM←RM), S
be 0.32±0.1, 0.42±0.1 and 0.60±0.2 Gy,
and
S
are
the
S
values
from
RM,
h
(RM←h)
(RM←RB)
respectively(table2).
andRBtoRMrespectively.
Nostatisticallysigni$icantdifferencewasfound
Radiation dose from residual thyroid tissue
between the effective half-lives as a
to red marrow should be neglected
function of administered activity, and between
because is low in non-metastatic thyroid
the effective half-lives and bone marrow
carcinoma patients. When calculating radiation
radiation dose (p>0.05). According to the
absorbed dose for bone marrow (RM-red
(16)
ANOVA statistic, signi$icant differences were
marrow),theBMdoseformulaisused .
found between administered activity and bone
marrowradiationdose(p<0.05).
D(BM)=[AD (RM)xS(RM←RM)]+[AD (RM)xS(RM←RB)]
PatientsweregroupedonthebasisoftheirTg
levels
and tumor diameters were compared
Bloodsampleswerecollectedat2,19,24,48,
131
using Spearman’s correlation. Signi$icant
72, 96, 120 and 144 hours after
I
correlations were found between administered
administration, and tubes were $illed with 1 ml
activity,Tglevelsandtumordiameters(table3).
of blood and measured in a well counter
101
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[ DOI: 10.18869/acadpub.ijrr.14.2.99 ]
Parlak et al. / Bone marrow radiation dosimetry 131I …
Table 2. Correla on with effec ve half-life and bone
marrow doses of ac vity.
Groups
1
2
3
Effec ve Half Life (h)
20.57±5.4
17.75±5.8
18.70±3.9
Bone Marrow Dose(Gy
0.32±0.1
0.42±0.1
0.60±0.2
DISCUSSION
Table 3. Tg levels and tumor diameters of pa ents.
Thyroglobulin
(Tg) levels
(ng/ml)
Tumor
diameters
(cm)
Administered
Ac vity (MBq)
Number
of
Pa ents
3700
5550
7400
3700
5550
7400
48
18
17
45
26
12
Tg levels
and tumour
diameters
(Mean±SD)
12±12.5
399±185.1
313±586
0.87±1.75
1.50±3.06
1.44±4.16
P
Value
0.010
0.04
Nuclear medicine physician should calculate
standard dose formula must decrease the
the necessary activity to be administered to
absorbed dose to bone marrow. Lassman has
patientsinordertoobtainsuccessivetreatment.
investigated the same methodology in his 2010
Therearethreemethodsfordeterminingthe131I
study (2)and mentioned the disadvantages of $ix
activity. The are $ixed empirical dose method,
dose formula and the serious potential side
dosimetry based approach and fractional dose
effects that arise from lackness the
method(3).
patient-speci$icparameters.
Themostcommonandsimplestmethodisto
Somestudiesproposedthat,thedose-limiting
administer a $ixed empirical dose regardless of
131I uptake of tumour lesion. Doses are usually
toxicity of RAI treatment is mainly on the bone
determined by disease extent. Conventionalmarrow(BM),andthelimithasbeensetinvolve
the dose (administered activity) that delivers 2
doses are 3.7–6.5 GBq (100–175 mCi) for
cervicallymphnodemetastasis,and5.5–7.4GBqGy(200rad)tothebloodasanequivalentofBM
and whole-body retention of <4.44 GBq (<120
(150–200mCi)fordistantmetastasis (17).Inour
mCi)at48h,andlunguptakeshouldbelessthan
clinic, doses of treatment are 3.7 GBq dose for
3GBq(~80mCi)(7,21).
non-metastatic, 5.5 GBq dose for lymph node
At present, differential thyroid cancer is
metastasis,7.4GBqfordistantmetastasis.
treated
Using $ix-administered activity fails to with standard empirical activities with
signi$icant disadvantages. Exposure to radiation
consider the individuality of patients in which
resulting from standard activities is
there is no consideration for patient speci$ic
heterogeneous and the radiation dosage
factors; such as reliable and universal
absorbedbythebloodchangeableduetovariety
adjustmentsbasedonthepatientweight,ageor
of many factors such as (patients’ Body Mass
gender of the patient or any other patient
Index, renal clearance) (20). In thyroid cancer
speci$ic factors for that matter. In addition to
patients treated during hypothyroidism, blood
this, in the limitations of $ix-administered
dose may increase above 2 Gy after the
activity, it lacks the description of the
administrationof7.4GBq(200mCi) (22).Incase
radioiodine biodistribution in the body, slow
of a low blood dose and high renal clearance
and long component of radioiodine clearance
inadequate accumulation of radioiodine should
from the kidneys, and the transport of
be expected in the target tissue. Hence, this
radioiodine in the blood stream are not
situation can be resolved by increasing the
determinant factors. However, literature shows
therapeuticactivity.
that all of these factors are critical to the
(18-20)
Patient speci$ic therapy depending on
. Excessive
ef$iciency of treatment
pre-treatment dose calculations for bone
radioiodine administration can lead to side
marrow absorbed dose and the target dose per
effects in the short or in the long term such as
activity enhance the possibility to calculate the
the induction of bone marrow suppression. As
optimum activity to ablate all remnant thyroid
bonemarrowisverysensitivetotheradiation;it
lesions without exceeding the bone marrow
seems that in some patients who are subjected
tolerated dose and also to determine the
to low activity administration less than the
Int. J. Radiat. Res., Vol. 14 No. 2, April 2016
102
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[ DOI: 10.18869/acadpub.ijrr.14.2.99 ]
Parlak et al. / Bone marrow radiation dosimetry 131I …
necessary activity to full$il effective tumor
basis of their Tg levels and tumor diameters,
regression. Hanscheid conducted a study in
then the relation between two groups was
2006,andstudiedthebloodsamplesofpatients
examinedbySpearman’scorrelation(table3).In
for blood doses $inding a range between 0.064
clinical practice, Tg levels are considered as a
and 0.35 mGy/MBq. Bone-marrow absorbed
parameterindeterminingtheamountofactivity
dose was found 0.074 mGy/MBq by
tobeadministered.However,thedetermination
Willegaignonafterthe3.7GBq.Intheourstudy,
of treatment dose is not only dependent on the
bone-marrow absorbed dose was found 0.086
Tg level. For patients with a high Tg level, the
mGy/MBq for 3.7 GBq, 0.075 mGy/MBq for 5.5
blooddoseswerehigh,aswell.
GBqand0.081mGy/MBqfor7.4GBq.
De Keizer et al. conducted a study on bone
CONCLUSION
marrow dosimetry in 2004 (10), none of the
patientsinthepresentstudywentoverthelimit
of 2 Gy. They collected samples of blood and
It is concluded that effective half-life of the
urinefromthyroidcancerpatientsandanalyzed
radioiodineisnotassociatedwiththeamountof
activity,ageandgenderofpatients.Theamount
the samples for renal clearance of iodine and
of activity was correlated with bone marrow
bone marrow absorption of radiation. Four
patients,intheirstudy,werereportedtohavea
doses and our $indings can be used as an
extrapolation coef$icient to determine the total
whole-blood absorbed dose higher than the
bone marrow dose in metastatic and nonthreshold level of 2 Gy. The doses of bone
metastaticpatients.
marrowradiationhavebeencalculatedusingthe
MIRD method and their results were between
Weusedadosimetricmethodologybasedon
(10)
which is
the MIRD technique and our $indings
the ranges of 0.28 Gy to 1.91 Gy
slightly higher than our results. In the study,
demonstrated that BM doses are in the safety
limit. Despite of the administrated doses were
MIRDOSE3programwasusedfortotalbodyand
redmarrow dosimetryfor dosages reductionin
withintheradiationlimits,ithasbeenconcluded
apatientwithhemodialysiswhopresentedasa
that the $irst dose in the treatment may be
(23)
casereportanddonebyKaptein .
increased in patients with metastatic thyroid
AnotherstudywasconductedbyDornetal.in
cancer.
2003 (15) withthyroidcancerpatientsandusing
the
MIRDOSE3
method
that
found
Con lictofinterest: Declarednone.
dosimetry-guided high-dose (Bone marrow
absorbed dose up to 3 Gy). In their study, no
permanent BM suppression was observed in
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