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Effective Half-life of Iodine-131 in Graves' Disease and Toxic Nodular Goiter Patients, Exercises of Oncology

Texas State Technical College-WacoOncology

A study that aimed to evaluate the effect of half-life determination and differences in the half-life of Iodine-131 between patients with Graves' disease and toxic nodular goiter, as well as the influence of antithyroid drugs on iodine uptake. The study found significant differences in effective half-life between the two groups and the impact of antithyroid drugs on patients' half-life.

What you will learn

  • What is the difference in effective half-life between patients with Graves' disease and toxic nodular goiter?
  • What is the clinical significance of effective half-life determination in radioiodine therapy?
  • How does antithyroid drug use impact the effective half-life of Iodine-131 in patients?

Typology: Exercises

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CONCLUSION
Iodine-l23-@-CIT SPECT imaging in healthy humans dem
onstrates low test/retest variability and good reliability across
several outcome measures. This supports the feasibility of
utilizing [‘23I]f3-CITfor SPECT measurementof dopamine
transporters in the evaluation of neuropsychiatric illness affect
ing dopamine neuronal function. Further studies of the variabil
ity of these measures in patient populations would be useful for
better delineating the utility of [ 231](3-CIT SPECT for serial
evaluations in patients groups.
ACKNOWLEDGEMENTS
This work was supported by funds from the Department of
Veterans Affairs, the Public Health Service (MH30929), and a
gift from Philip and Rose Hoffer. We thank Eileen Smith and
Gary Wisniewski for technical support, Lynn Pantages-Torok
and Quinn Ramsby for data analysis and Morgan Stratton for
radiochemistry technical help.
REFERENCES
1. Neumeyer JL, Wang 5, Milius RA, et al. Iodine-l23-2-@3-Carbomethoxy-3-@-(4-
iodophenyl)-tropane (@-C1T):high affinity SPECT radiotracer ofmonoamine reuptake
sites in brain. JMed C/tern 1991;34:3144—3146.
2. Innis R, 5eibyl J, 5canley B, et a!. SPECT imaging demonstrates loss of striatal
monoamine transporters in Parkinson's disease. Proc Nat! Acad Sc! 1993;90:l 1965—
I1969.
3. LaruelleM, BaldwinR, Malison R. et al. SPECT imagingofdopamine and serotonin
transporters with [‘23I]@-C1T:pharmacological characterization of brain uptake in
nonhuman primates. Synapse 1993;13:295—309.
4. Seibyl J, Wallace E, Smith E, et al. Whole.body biodistribution, radiation absorbed
dose, and brain SPECT imaging with [‘23lJ@-CITin healthy human subjects. J Nuc!
Med 1994;35:764—770.
5. LaruelleM, WallaceE,SeibylJ,et al.Graphical,kineticandequilibriumanalysesof
in vivo [‘23I]@..CITbinding to dopamine transporters in healthy human subjects. J
Cereb Blood F!ow Metab 1994;14:982—994.
6. BaldwinR,Zea-PonceY, ZoghbiS. Ctal.Evaluationof themonoamineuptakesite
ligand[‘231]methyl3@-(4-iodophenyl>.tmpane.2@-carboxylate(‘231)13-CITin nonhu
man primates: pharmacokinetics, biodistribution and SPECT brain imaging coregis
tered with MRI. Nuci Med Biol l993;20:597—606.
7. Chang LI. A method for attenuation correction in computed tomography. IEEE Trans
Nuc! Sc! 1987;N5-25:638—643.
8. Gandelman M5, Baldwin RM, Zoghbi 5S, Zea-Ponce Y, Innis RB. Evaluation of
ultrafiltration for the free fraction determination of SPECT radiotracers: b-CIT. IBF
and iomazenil. JPharm Sci 1994;83:1014—l019.
9. LaruelleM, BaldwinRM,RattnerZ, Ctal. SPECTquantificationof [‘231]iomazenil
binding to benzodiazepine receptors in nonhuman primates. I. Kinetic modeling of
single bolus experiments. J Cereb Blood Flow Metab 1994;l4:439—452.
10. LevenbergK. A methodfor thesolutionof certainproblemsin leastsquares.Quart
App!Math 1944;2:l64—l68.
11. PatlakCS, Balsberg RG, FenstermacherJD. Graphicalevaluationof blood to brain
transfer constants from multiple time uptake data. J Cereb Blood Flow Metab
1983;3:l—7.
12. Kirk R. Experimental design: proceduresfor the behavioral sciences. Pacific Grove,
CA:Brooks/ColePublishing,Co., 1982.
13. SorensenJA,PhelpsME.PhysicsinNuclearMedicine.SecondEdition,Philadelphia:
W.B.SaundersCo.;1987.
14. NeumeyerJL, Wang5, Gao Y, MiliusRA, et al. N-w-fluoroalkylanalogsof
(1R).2@-carbomethoxy-3@..(4-iodophenyl)tropane (a-CIT): radiotracers for PET and
SPEcT imaging of dopamine transporters. J Med Chem 1994;37:1558—156l.
15. ZelnikN, Angel I, Paul SM, KleinmanJE. Decreaseddensityof human striatal
dopamine uptake sites with age. Eur J Pharmacol 1986;l26:l75—176.
16. DeKeyserJ,EbmgerG, VauquelinG.Age-relatedchangesinthe humannigrostriatal
dopaminergic system. Ann Neurol 1990;27:157—l6l.
17. Van Dyck C, Seibyl J, Malison R, et al. Age-relateddecline in dopaminetransporter
binding in human striatum with [‘23I]@-CITSPECT [Abstract]. Soc Neurosci 1994;
20:387.
nodular goiter (mean 6.0 days) and a skewed distribution in toxic
nodulargoiter. Patientspretreatedwith antithyroiddrugs had shorter
1311 half-lives in both categories. Ten percent ofthe patients required
more than one treatment; 94% of the patients with Graves' disease
and 45% with toxic nodular goiter had thyroxine substitution 1-5 yr
after treatment. Conclusion: A dose calculation method that uses
three uptake measurements provkles SUfficIent data about the
effecthie half-lifeof 1311in the thyroki. There is conskierable differ
ence in the half-lifebased on the diseasebeing treated (Graves'
diseaseor toxic nodular goiter).The 1311half-lifealso is shorter after
pretreatment with anti-thyroid drugs. Thus, the simpler method
leadsto significant uncertainty,leading to over- as well undertreat
ment of the patient
Key Words hyperthyr@dism;iodine-131; effective half-life;Graves'
disease;toxic nodular goiter
J Nuci Med 1996 37228—232
Hypertiiyroidismmaybetreatedinthreeways:medical
therapy with antithyroid drugs, radioiodine therapy or surgery.
Therapeutic strategies vary within and between different coun
tries. In many clinics, radioiodine treatment is the most com
monly used method for treating adult patients with hyperthy
Our goals were to evaluatethe effect of half-life determinationand
differences in the half-life of 1311between patients with Graves'
disease and toxic nodular goiter, and the influence of antithyrc@d
drugs on iodine uptake. Methods We reviewed the records of 555
patientswho had recsived radioiodinetreatmentfor Graves'disease
andtoxic nodulargoiterto analyzeiodineuptake, half-lifevaluesand
pretreatmentwith antithyroid drugs. Two different methods of dose
calculationwerecompared:one usingrepeateduptakemeasure
ments at24 and 48 hr and 4 or 6 daysto define the effectivehalf-life.
The othermethod assumeda half-lifeof 5 days and uptakeat 24 hr
only. All patents were treated according to the first method. A
follow-up questionnairewassent to 327 patients(238 responders)to
assessthe treatment outcome. Results After comparingthe results
ofthetwo methods,we foundthatrepeatuptakemeasurements
and determinationof effectivehalf-liferesultsinadministeredactiv
ities that differ considerably from those calculated when an as
sumed, fixed half-life and a single uptake measurementare used.
The simpiar method would lead to over- as well as undertreatment
of the patient. There was a functional difference between patients
with Graves' disease and toxic nodular goiter, as reflected by the
shorter 1311half-life in Graves' disease (mean 5.0 days) than toxic
ReceivedOct.5,1994;revIsionacceptedJuL5,1995.
For correspondence or reprints contact: Dr. Gertrud Berg, Department of Oncology,
SahlgrenskaUniversityHospital,S-41345GOteborg,Sweden.
228 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 2 •February1996
Iodine- 131 Treatment of Hyperthyroidism:
Significance of Effective Half-life Measurements
Gertrud E.B. Berg, Annika M.K. Michanek, Enk C.V. Holmberg and Margareta Fink
Thyroid Unit, Department of Oncology, Oncology Center and Department ofMedical Physics and Medical Engineering,
Sahlgrenska University Hospital, Goteborg, Sweden
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pf4
pf5

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CONCLUSION

Iodine-l23-@-CIT SPECT imaging in healthy humans dem onstrates low test/retest variability and good reliability across

several outcome measures. This supports the feasibility of

utilizing [‘23I]f3-CITfor SPECT measurementof dopamine

transporters in the evaluation of neuropsychiatric illness affect

ing dopamine neuronal function. Further studies of the variabil ity of these measures in patient populations would be useful for better delineating the utility of [ 231](3-CIT SPECT for serial evaluations in patients groups.

ACKNOWLEDGEMENTS This work was supported by funds from the Department of Veterans Affairs, the Public Health Service (MH30929), and a gift from Philip and Rose Hoffer. We thank Eileen Smith and Gary Wisniewski for technical support, Lynn Pantages-Torok and Quinn Ramsby for data analysis and Morgan Stratton for radiochemistry technical help.

REFERENCES

1. Neumeyer JL, Wang 5, Milius RA, et al. Iodine-l23-2-@3-Carbomethoxy-3-@-(4- iodophenyl)-tropane (@-C1T):high affinity SPECT radiotracer ofmonoamine reuptake sites in brain. JMed C/tern 1991;34:3144—3146. **2. Innis R, 5eibyl J, 5canley B, et a!. SPECT imaging demonstrates loss of striatal monoamine transporters in Parkinson's disease. Proc Nat! Acad Sc! 1993;90:l 1965— I1969.

  1. LaruelleM, BaldwinR, MalisonR. et al. SPECTimagingofdopamine andserotonin** transporters with [‘23I]@-C1T:pharmacological characterization of brain uptake in nonhuman primates. Synapse 1993;13:295—309.
  2. Seibyl J, Wallace E, Smith E, et al. Whole.body biodistribution, radiation absorbed

dose, and brain SPECT imaging with [‘23lJ@-CITin healthy human subjects. J Nuc! Med 1994;35:764—770.

5. LaruelleM, WallaceE, SeibylJ,et al. Graphical,kineticandequilibriumanalysesof in vivo [‘23I]@..CITbinding to dopamine transporters in healthy human subjects. J Cereb Blood F!ow Metab 1994;14:982—994. 6. BaldwinR,Zea-PonceY, ZoghbiS. Ctal. Evaluationof themonoamineuptakesite ligand [‘231]methyl3@-(4-iodophenyl>.tmpane.2@-carboxylate(‘231)13-CITin nonhu man primates: pharmacokinetics, biodistribution and SPECT brain imaging coregis tered with MRI. Nuci Med Biol l993;20:597—606.

  1. Chang LI. A method for attenuation correction in computed tomography. IEEE Trans Nuc! Sc! 1987;N5-25:638—643. 8. Gandelman M5, Baldwin RM, Zoghbi 5S, Zea-Ponce Y, Innis RB. Evaluation of ultrafiltration for the free fraction determination of SPECT radiotracers: b-CIT. IBF and iomazenil. JPharm Sci 1994;83:1014—l019. 9. LaruelleM, BaldwinRM,RattnerZ, Ctal. SPECTquantificationof [‘231]iomazenil binding to benzodiazepine receptors in nonhuman primates. I. Kinetic modeling of **single bolus experiments. J Cereb Blood Flow Metab 1994;l4:439—452.
  2. LevenbergK. A methodfor thesolutionof certainproblemsin leastsquares.Quart** App!Math 1944;2:l64—l68. 11. PatlakCS, Balsberg RG, FenstermacherJD. Graphicalevaluationof blood to brain transfer constants from multiple time uptake data. J Cereb Blood Flow Metab **1983;3:l—7.
  3. Kirk R. Experimental design: proceduresfor the behavioral sciences. Pacific Grove, CA:Brooks/ColePublishing,Co.,1982.**
  4. SorensenJA,PhelpsME.Physicsin NuclearMedicine.SecondEdition,Philadelphia: **W.B.SaundersCo.;1987.
  5. NeumeyerJL, Wang5, Gao Y, MiliusRA, et al. N-w-fluoroalkylanalogsof** (1R).2@-carbomethoxy-3@..(4-iodophenyl)tropane (a-CIT): radiotracers for PET and SPEcT imaging of dopamine transporters. J Med Chem 1994;37:1558—156l.
  6. ZelnikN, Angel I, Paul SM, KleinmanJE. Decreaseddensityof humanstriatal dopamine uptake sites with age. Eur J Pharmacol 1986;l26:l75—176.
  7. DeKeyserJ, EbmgerG, VauquelinG. Age-relatedchangesinthehumannigrostriatal dopaminergic system. Ann Neurol 1990;27:157—l6l. 17. Van Dyck C, Seibyl J, Malison R, et al. Age-relateddecline in dopaminetransporter binding in human striatum with [‘23I]@-CITSPECT [Abstract]. Soc Neurosci 1994; 20:387.

nodular goiter (mean 6.0 days) and a skewed distribution in toxic nodulargoiter. Patientspretreatedwith antithyroiddrugs had shorter 1311 half-lives in both categories. Ten percent ofthe patients required more than one treatment; 94% of the patients with Graves' disease and 45% with toxic nodular goiter had thyroxine substitution 1-5 yr after treatment. Conclusion: A dose calculation method that uses three uptake measurements provkles SUfficIent data about the effecthie half-life of 1311in the thyroki. There is conskierable differ ence in the half-life based on the disease being treated (Graves' diseaseor toxic nodulargoiter).The 1311half-lifealso is shorter after pretreatment with anti-thyroid drugs. Thus, the simpler method leads to significant uncertainty,leading to over- as well undertreat ment of the patient Key Words hyperthyr@dism;iodine-131; effective half-life;Graves' disease;toxic nodular goiter J Nuci Med 1996 37228—

Hypertiiyroidismmaybetreatedinthreeways:medical therapy with antithyroid drugs, radioiodine therapy or surgery. Therapeutic strategies vary within and between different coun tries. In many clinics, radioiodine treatment is the most com monly used method for treating adult patients with hyperthy

Our goals were to evaluatethe effect of half-life determinationand differences in the half-life of 1311between patients with Graves' disease and toxic nodular goiter, and the influence of antithyrc@d drugs on iodine uptake. Methods We reviewed the records of 555 patientswho had recsivedradioiodinetreatmentfor Graves'disease and toxic nodulargoiterto analyzeiodineuptake,half-lifevaluesand pretreatmentwith antithyroid drugs. Two different methods of dose

calculationwerecompared:one usingrepeateduptakemeasure

ments at 24 and 48 hr and 4 or 6 days to definethe effectivehalf-life. The other method assumed a half-lifeof 5 days and uptake at 24 hr only. All patents were treated according to the first method. A follow-up questionnairewas sentto 327 patients(238responders)to assessthe treatment outcome. Results After comparingthe results ofthetwo methods,we foundthatrepeatuptakemeasurements and determinationof effectivehalf-liferesultsinadministeredactiv ities that differ considerably from those calculated when an as sumed, fixed half-life and a single uptake measurementare used. The simpiar method would lead to over- as well as undertreatment of the patient. There was a functional difference between patients with Graves' disease and toxic nodular goiter, as reflected by the shorter 1311half-life in Graves' disease (mean 5.0 days) than toxic

ReceivedOct.5, 1994;revIsionacceptedJuL5, 1995. For correspondence or reprints contact: Dr. Gertrud Berg, Department of Oncology, SahlgrenskaUniversityHospital,S-41345GOteborg,Sweden.

228 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 2 •February

Iodine- 13 1 Treatment of Hyperthyroidism:

Significance of Effective Half-life Measurements

Gertrud E.B. Berg, Annika M.K. Michanek, Enk C.V. Holmberg and Margareta Fink Thyroid Unit, Department of Oncology, Oncology Center and Department ofMedical Physics and Medical Engineering, Sahlgrenska University Hospital, Goteborg, Sweden

roidism and is generally accepted as safe, convenient and of low cost(1—3). Several years ago, much effort was made to calculate the dose of radioiodine needed to render the patient euthyroid and to avoid hypothyroism after treatment. This has proven to be difficult, however, since hypothyroidism is also the result of progressive changes in the thyroid cells ofpatients with Graves' disease and since hypothyroidism will eventually occur at a rate of about 3% per year regardless of the therapeutic course (4,5). The consequence of giving a small dose with the intention to avoid hypothyroidism is that the patient will remain toxic for a long period of time and often repeated treatments are required, resulting in larger accumulated radiation doses. In many clinics, a sufficiently high dose of radioiodine is administered to make the patient euthyroid within a reasonable time and thyroxine is substituted within a short period of time after treatment (6—9). Much of the work done in the 1950s and 1960s on kinetic studies and the importance of effective half-life measurements to calculate the absorbed dose to the thyroid is still of value (10, 11 ). When the intention is to give a higher absorbed dose to the thyroid to avoid retreatment, the documented formulas for calculation are now actualized with the aim of calculating the minimum activity to achieve the new goal. At our institution, the delivered absorbed dose method (12) for dose calculation has been used for years. This method includes uptake measurements at three different times to calcu late the absorbed dose. Therefore, our goals were:

  1. To study the effect of effective half-life determination for absorbed dose calculations compared to a simpler method

with a fixed effective half-life.

  1. To determine whether there is a difference in effective half-life between patients with Graves' disease and toxic

nodular goiter.

3. To investigateif the effective half-life of the radioisotope is influenced by the use of antithyroid drugs before radioiodine treatment.

METhODS

Patients

From 1989 through 1992, 1036 patients (aged 25—89yr) were

admitted for hyperthyroidism and, after investigation, 789 patients were found to have hyperthyroidism that required radioiodine treatment. Records from 754 patients were examined, and the diagnoses of these patients were: Graves' disease (n 456), toxic nodular goiter (n = 219) and unilateral toxic adenoma (n = 52). Twenty-seven patients had previously undergone surgery for hy perthyroidism. The records of patients with Graves' disease and toxic nodular goiter containing complete information about uptake measure ments were included in the final analysis (n = 555). Patients underwent routine laboratory testing, including pregnancy testing when appropriate, and were treated as outpatients, with the excep

tion of a few elderly patients in need of hospital care.

Hyperthyroidism was diagnosed based upon biochemical test results, uptake measurements and thyroid scan results. The diag nosis of diffi.ise or nodular goiter was based upon the thyroid scan image and thyroid mass was estimated by palpation and by the thyroid scan. After radioiodine treatment, follow-up was performed by the admitting physician. In order to register the clinical outcome of the radioiodine treated patients, a questionnaire was sent to study patients aged 70 yr and younger (n = 327). The patients were asked

if they had receivedadditionaltreatmentfor hyperthyroidism,if they had thyroxine substitution and when this therapy had started.

Biochemical Methods For most patients, we determined serum TSH and T3 with reagents from Diagnostic Products Corp. (Los Angeles, CA; “NFIS-TSHRIA Double Antibody' ‘and ‘‘T3RIA Double Anti

body,―respectively). In most patients, free T4 was determined

with an analog assay. Uptake measurements were performed with a 2-inch Nal crystal after oral administration of 0.5 MBq radioiodine. The crystal was centered at 10 cm distance from the trachea or neck phantom. The

measuring time was 60 sec. Background was measured for 10 mm

in the room. Thyroid uptake was determined with the formula:

1311 uptake = ((neck counts —background counts)! (standard counts —background counts)) X 100%.

To confirm thyroid uptake @“@Tcimaging was performed with a gamma camera 15 mm after intravenous administration of 150 MBq [99mTc1pertec@etate.

Clinical Protocol The patient received an oral test activity ofO.5 MBq (0.014 mCi) 131! and uptake measurements were performed after 24 and 48 hr and 4 or 6 days. If antithyroid drugs were used before treatment, the patient ceased its intake 7 days before administration ofthe test dose. Most patients received thiamazole. Two days after the test dose, a thyroid [@Tc]pertechnetate scan was obtained. Therapeu tic radioiodine was given orally in an aqueous solution. The absorbed dose to the thyroid was defined for each patient and was in the range of 100—120Gy. We used two methods to determine dose calculations, which are defined as follows. Method A. The activity administered to the patient was calcu lated according to the following formula:

Activity A (MBq) 23.4X mass(g) x absorbeddose(Gy) estimated uptake at time zero (%) X effective half-life (days)'

in which 23.4 is a physical constant describing tissue-absorbed fractions expressed in MBq!Gy. Effective half-life (days) = (Tphys x Thiol)!(Tphys+ Thiol),inwhichThiolisthebiologicalhalf-life

calculated from uptake values at 24 and 48 hr and 4 or 6 days and

the physical half-life of ‘@‘Iwhich is 8 days. In those cases where the retained activity increased instead of declining during the

period of measurement, a fixed value of effective half-life of 7.

days was chosen. Method B (Simpl@fled Method). We used the 24-hr uptake measurement and a fixed effective half-life of 5 days to recalculate the required activity to obtain the defined absorbed dose for each patient with the following formula:

23.4X mass(g x absorbeddose(Gy) Activity B (MBq) uptake at 24 hr X 5 (days)

Statistical Analysis

Student's t-test and a scatter diagram were used for comparison

between the two methods (13).

RESULTS Treatment Outcome Of the 555 patients, 389 were classified as having Graves' disease and 166 as having toxic nodular goiter. Five hundred two patients (90.5%) were treated for the first time, 5 1 (9.2%) were retreated and 2 (0.4%) received a third treatment. Eight

EFFECTIVE HALF-LIFE AND IoDmiE-l 3 1 TREATMENT •Berg et al. 229

0 Q

8

@ 0 0 0 0 300 2@0 0 150 @@@00000@

@-15O 0c@c@0 0

•g-300 0

@@@@ -

•@ 0 200 400 600 800 1000 0 0 E 2 outliers

300 @ 0 0 C 150 ; 00 @ 0

@ 00 00

-600 0 °

@@ -750 I I

AverageactivitybymethodA andmethodB (MBq)

70

60 Cl) C 0 50

Q- 40 (Cl . z a 30 20- 10-

(0(

n= (

g@

DifterenceinActivity(%)

(^0) ‘@

FIGURE4. DifferenceinadministeredactMty(%)between MethodsAand B in patientswith Graves'disease.A = activity (MBq).Calculationis based on 24-hr,48-hrand4 or6 daysuptakemeasurementstodeterminetheeffective half-life.B = activity(MBq).Calculationisbasedonafixedvalueof effective half-lifeof 5 days. 0 q@o 1%

the scatter of difference increases as the activity increases. The mean difference was —7.4(s.d. = 111.1) for patients with

Graves' disease and —135.6 (s.d. = 153.4) for toxic nodular

goiter patients. The following two examples emphasize the importance of the effective half-life in dose calculation: Example 1. A patient with Graves' disease with a thyroid mass of 50 g and uptake measurements of 43%, 27% and 18% at 24 and 48 hr and 4 days will have an estimated uptake at time zero of 64% and an effective ‘@‘Ihalf-life of 1.6 days. The

selection of 100 Gy as the absorbed dose to the thyroid for

treatment will result in the patient receiving 1 143 MBq (30. mCi) using method A and 539 MBq (14.6 mCi) with method B. Example 2. A patient with toxic nodular goiter with a thyroid mass of 40 g and uptake values of 34%, 41% and 40% after 24 and 48 hr and 4 days, respectively, will have an estimated uptake at time zero of 42% and a 131!half-life of 7.5 days. If 120 Gy are chosen for treatment, Method A results in 356 MBq (9.6 mCi) while Method B will give as much as 660 MBq (17. mCi).

FIGURE6.DifferenceagainstmeanforpatientswithGraves'disease(above) andtoxicnodulargoiter(below).

DISCUSSION

When radioiodine therapy was introduced more than 50 years ago, it was first given to elderly patients since it was suspected

to induce cancer and genetic damage (12). These hazards,

however, have proven to be negligible and younger adult patients are being prescribed this treatment (14,15). In Sweden, most centers choose 35 yr as the lower age limit for radioiodine treatment. This policy is supported by recently published Swedish multicenter studies (16, 1 7), in which 10, patients aged 50—75receiving radioiodine therapy were studied to determine later incidences of cancer. With the exception of a possible small risk for stomach cancer, no indications of radiation-related cancer risk were found. The study supports the view that radioiodine therapy is a safe method for adult patients, but it also stresses the importance of choosing the lowest possible administered activity to achieve the desired clinical effect. This is especially important given the fact that younger and younger adults are admitted for radioiodine treatment (2). Determining the half-life is an important factor in dose calculation, in that the effective half-life may differ, with a range from 1.6 to 7.5 days, giving a possible difference in the formula by a factor of 4.6. This contributes to a greater error in the formula than that expected from thyroid volume determi nation, which is estimated to be a factor of about 1.5 and is

considered a significant source of error (18).

The use ofthe delivered absorbed dose method results in low frequency of repeat treatments (10% in our patient population),

20.

Cl) C S (Cl

@ 10-

5-

.. , Difference in Activity (%)

FiGURE5. Differenceinadministeredactivity(%)between MethodsAand B in patientswithtoxicnodulargoiter.A = activity(MBq).Calculationis based on 24-hr,48-hrand4 or 6 day uptakemeasurementsfor determinationof effectivehalf-life.B = activity(MBq).Calculationis basedonafixedvalueof effectivehalf-lifeof 5 days.

EFFECTIVE HALF-LIFE AND I0DmiE-1 3 1 TREATMENT •Berg et al. 231

although the mean accumulated administered activity is lower than that from fixed ablative doses (6—8). We compared our results to those of other investigators who have used the delivered absorbed dose method to determine the half-life and found a correlation between clinical outcome and the absorbed dose. Thus, our chosen absorbed dose is 100— Gy, which results in repeat treatment rates of 8% in our Graves' disease patients and 13% in our toxic nodular goiter patients. These measures are comparable to values reported by Hoim et al. (4) and Kung et al. (19): 44% repeat treatments when using 60—100Gy (4) and 40% of the patients still toxic 1 yr after therapy after an 80-Gy dose (19). The prevalence of nodular goiter is higher in iodine-poor areas such as central Europe than in iodine-rich areas such as the U.S. In Sweden, the iodine supply has become sufficient during the last decades, but we still fmd a high proportion of nodular goiter (30%) in our population compared to the U.S.

(20). The differencein ‘31Ihalf-livesfor nodularanddiffuse

goiter in this study stresses the importance ofusing scintigraphy to differentiate between the two conditions, which is not always easy by palpation alone (21 ). The higher rate of treatment failure among toxic nodular goiter patients may be explained by the fact that new hot nodules may develop in the thyroid after treatment in areas that did not take up radioiodine primarily.

In our study,we found that patientstaking antithyroid drugs

before treatment have a significantly shorter effective half-life and, therefore, a faster turnover of radioisotope than untreated patients. The reason for this may be the behavior of the

antithyroid drug per se, which decreases the protein-bound

iodine fractionin the gland. Anotherpossible explanationis that

the illness might have been considered more serious among the pretreated patients and a shorter half-life would therefore be suspected in this category. Regardless of the reason, a short effective half-life could result in undertreatment if it is not considered in the dose-calculation. This perhaps explains why pretreated patients have been shown to have a higher frequency of radioiodine therapy failure (22,23).

CONCLUSION We have shown that measuring the effective half-life is important to determining the administered activity. The deliv ered absorbed dose methodology for dose calculation can be optimized for individual patients. Therefore, differences in iodine intake, thyroid hyperactivity and prior treatment with antithyroid drugs will be considered. Use of this method of

calculation means that the patient will have to come to the

hospital four times within a week for the dose calculation and treatment. Although this procedure is not laborious for the physician, especially when using computerized calculation, it does require extra effort from the patient. We are sure, however,

that any inconvenience will be readily accepted by the patient

once they know that the method results in more accurate treatment.

ACKNOWLEDGMENTS The authors thank Dr. Stare Lindberg, former head of the Department of Nuclear Medicine, Sahlgrenska Hospital, who

introduced us to the dose calculation method.

This study was supported by the King Gustav V Jubilee Clinic Cancer Research Foundation, Gothenburg, Sweden.

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232 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 2 •February