EANM Procedure Guideline For Therapy with Iodine-131

I.

PURPOSE
The purpose of this guideline is to assist nuclear medicine
practitioners in
1.

evaluating patients who might be candidates for therapy

with iodine-131 (131I) for benign or malignant conditions

II.

2.

providing information for performing this treatment.

3.

understanding and evaluating the sequelae of therapy.

BACKGROUND
A.

Definitions
1.

I-131 is a beta-emitting radionuclide with a physical

half-life of 8.0 days, a principal gamma ray of 364
keV and a principal beta particle with a maximum
energy of 0.61 MeV, an average energy of 0.192
MeV and a range in tissue of 0.8 mm.

2.

Therapy in this context means the oral administration

of 131I as sodium iodide.

3.

Benign conditions in this context mean Graves

disease (diffuse toxic goitre), toxic or non-toxic
goitre, solitary hyperfunctioning toxic thyroid nodule
or benign thyroid remnants from cancer surgery.

4.

Malignant conditions include differentiated thyroid

cancer that accumulates radioiodine or functioning
thyroid cancer metastases.

B.

Background

Oral administration of 131I Iodide has been used to treat

benign and malignant conditions of the thyroid since the
1940s. Physicians responsible for treating thyroid disease
should have an understanding of the clinical
pathophysiology and natural history of the disease
processes, should be familiar with other forms of therapy
and should be able to collaborate closely with other
physicians involved in managing the patient. The treating
physician should either see patients in consultation with the
physician assuming overall management of the patients
condition or be prepared to assume that role. The
physician should be appropriately trained and
experienced in the safe use and administration of 131I
therapy.

Clinicians undertaking unsealed source therapy must be

knowledgeable about and compliant with all applicable
national and local legislation and regulations.

The facility in which treatment is administered must have

appropriate personnel, radiation safety equipment,
procedures available for waste handling and disposal,
handling of contamination, monitoring personnel for
accidental contamination and controlling contamination
spread.

III.

COMMON INDICATIONS
A.

Benign disease

1.

Hyperthyroidism
131I

may be indicated as the initial or secondary

treatment of Graves disease, toxic multinodular

goitre or solitary toxic thyroid nodule. Avidity of the
thyroid gland for iodide must be sufficient to permit
accumulation of an adequate radiation dose.

2.

Non-toxic multinodular/diffuse goitre

131I

therapy has been used successfully to diminish

the size of non-toxic multinodular/diffuse goitre.

3.

Post operative ablation of benign thyroid remnant

(s) after thyroidectomy.

a.

A minimum of four weeks should elapse

between surgery and radioiodine therapy to
allow endogenous levels of TSH to rise to 3050 ulU/ml. TSH may not rise to this level if a
large volume of functioning thyroid tissue
remains.

b.

Ability of the remnant to accumulate

radioiodine may be demonstrated by uptake
measurement or imaging

B.

MALIGNANT DISEASE

1.

Therapy of residual cancer, local and distant

metastases

The presence of thyroid tissue should be

documented, either by imaging or biopsy. A
rising thyroglobin titre is a useful indicator of
residual or recurrent thyroid cancer.

CONTRAINDICATIONS

1.

Absolute

Pregnancy; breastfeeding

2. Relative

Unmanageable urinary incontinence

Uncontrolled hyperthyroidism
Active thyroid orbitopathy

IV.

PROCEDURE
A.

Facility
The facilities required will depend on national legislation for
the emission of beta and gamma emitting
radiopharmaceuticals. If in-patient therapy is required by
national legislation, this should take place in an approved
facility with appropriately shielded rooms and en-suite
bathroom facilities. The administration of 131I should be
undertaken by appropriately trained medical staff with
supporting scientific and nursing staff.

B.

Patient preparation
1.

All patients:

a.

Should have given a clinical history and

undergone physical examination. Therapeutic
alternatives should be reviewed.

b.

Should have undergone Laboratory Medicine

testing appropriate to the condition with
results available to and reviewed by the
treating physician.

c.

Should receive written and verbal information

about the procedure prior to receiving
therapy. This information should include
details of the procedure, potential
complications, side effects, alternatives, and
expected outcome. Written informed consent
should be obtained.

d.

Should be instructed on how to reduce

unnecessary radiation exposure to family
members and members of the public. Written
instructions should be provided.

e.

Iodide-containing preparations, iodine

supplements, thyroid hormones and other
medications that potentially affect the ability
of thyroid tissue to accumulate iodide
must be discontinued for a sufficient time prior
to

131I

administration. (See table).

f.

Must not have received iodine-containing

radiographic contrast for at least three to four
weeks prior to planned 131I therapy. In patients
who have received large contrast loads or
who have renal dysfunction, more time may
be required. (See table).
DRUG INTERACTIONS

Type of medication
Antithyroid medication (e.g.

Recommended time of withdrawal

3-7 days

propylthiouracil
carbimazole)
Natural or synthetic thyroid hormone

2 weeks for tri-iodothyronine

( e.g. thyroxine, tri-iodothyronine)

4 weeks for thyroxine

Expectorants, vitamins, health food

1-2 weeks, depending on iodide

preparations,

content

Sodium iodide
Iodine containing medications (e.g.

Variable, 1-6 months

amiodarone)
Topical iodine (e.g. surgical skin

1-2 weeks

preparation)

Radiographic contrast agents

Intravenous or intrathecal ( water soluble)

3-4 weeks

Oral fat soluble ( e.g. cholecystography)

3 months

Oil based ( e.g. bronchography)

6-12 months

Myelographic ( oil based)

2-10 years

Table adapted in part from: Monograph: 131-I (iodide), European

Association of Nuclear Medicine

2.

For outpatients

a.

Regulations governing the maximum burden

of 131I and maximum dose rate at which a
patient may be released vary according to
national legislation.

b.

For patients with thyrotoxicosis, recent

measurements of thyroid hormone levels (T3
and/or T4) and thyroid stimulating hormone
(TSH) should be available. For patients with
thyrotoxicosis, avidity of the thyroid gland for
iodide must be established. This can be
achieved quantitatively by radioiodine
uptake measurements or qualitatively by
thyroid scintigraphy. These procedures will
exclude silent thyroiditis or factitious
thyrotoxicosis. If neck uptake is not seen, a
pelvic image may exclude struma ovarii.
Interfering drugs or antithyroid medication
should be withdrawn prior to uptake
measurements as outlined above.

c.

For patients with malignant conditions, thyroid

hormone medication must be withheld for a
time sufficient to permit an adequate rise in
TSH. This is at least ten days for triiodothyronine
(T3) and four weeks for thyroxine (T4). Patients
with a large burden of residual functioning
thyroid tissue may not have the desired rise in
serum TSH. Recombinant TSH may be used to

prepare patients for post surgical diagnostic

studies. Its role in preparing patients for high
activity 131I therapy is not established.

3.

For inpatients

a.

All patients

i.

Should be informed of the radiation

precautions required.

ii.

Any significant medical conditions

should be noted and contingency plans
made in case radiation precautions
must be breached for a medical
emergency.

iii.

Nursing personnel must be instructed on

radiation safety.

iv.

Nursing personnel may be provided

appropriate radiation monitors (film
badge, pencil dosimeters, etc.).

v.

Concern about radiation should not

interfere with the prompt, appropriate
medical treatment of the patient,
should an acute medical problem
develop.

b.

Patients undergoing ablation of thyroid

remnant

i.

Should be on a low iodide diet for

about one week prior to administration
of 131I therapy.

Dietary Sources of Iodide

Iodized salt
Milk/dairy products
Eggs
Marine seafood
Seaweed and kelp products
Bread made with iodide conditioners
Celery
Iodide containing multivitamins

ii.

At least four weeks should have elapsed

between surgery and thyroid ablation.

iii.

Imaging is essential to confirm the ability

of the tissue to take up 131I prior to
treatment

c.

Patients undergoing post-ablation therapy for

residual, recurrent or metastatic disease.

i.

Should be on a low iodide diet for

about a week prior to administration of
therapy.

ii.

Thyroid hormone medications must be

withheld for a time sufficient to permit
an adequate rise in TSH. This is at least
ten days for triiodothyronine (T3) and
four weeks for thyroxine (T4). Patients
with a large burden of residual
functioning thyroid tissue may not have
the desired rise in serum TSH.
Recombinant TSH may be used to
prepare patients for diagnostic studies
in the post-surgical setting. Serum TSH
levels should ideally be greater than 30
ulU/ml.

iii.

A running total of administered activity

of 131I should be kept in the patients
record.

iv.

Imaging is essential to confirm the ability

of tissue to take up 131I prior to
treatment. Measurement of serum
thyroglobin level is also useful.

C.

Information pertinent to performing the procedure

1.

For all patients

a.

Female patients who have a potential to bear

children should routinely be tested for
pregnancy within a few days before the
administration of the 131I treatment.
Occasionally, for social reasons (e.g., women
who have taken the vows of celibacy) a
pregnancy test may be omitted.

b.

All potentially breast feeding/lactating

women should be asked if they are breast
feeding/lactating. If so, breast-feeding should
stop and therapy delayed until lactation
ceases in order to minimize the radiation dose
to the breast. The patient may not resume
breast-feeding for that child. Breast-feeding
may resume with the birth of another child.

c.

Assurance that the patient is continent of

urine or that arrangements are made to
prevent contamination caused by
incontinence.

2.

For patients with thyrotoxicosis

a.

Prior therapy and results with previous

radioiodine (including amount administered),
thionamides or surgery should be
documented.

b.

Results of recent 24-hour RAIU or qualitative

evidence of iodide avidity of the thyroid.

c.

Estimated weight of gland based upon

imaging or palpation if calculation of
administered activity is to be performed.

d.

The presence or absence of nodules in the

thyroid and their degree of function should be
noted.

e.

3.

Concomitant medications.

For patients with malignancy

a.

Histologic diagnosis.

b.

Evidence of functioning residual benign or

malignant thyroid tissue.

c.

Total lifetime 131I administered activity may be

useful.

C.

Precautions

1.

For patients with thyrotoxicosis

a.

Recent thionamide therapy usually increases

radioresistance by causing rapid turnover of
thyroidal iodine and by other mechanisms.
This may require a compensatory increase in
administered activity.

b.

Hyperthyroid crisis can be precipitated inpatients with large iodide avid multinodular
glands who are given large administered
activities. Such patients and patients who are
elderly, who suffer from known heart disease
or have a history of congestive heart failure
may need to be pre-treated with betablockers and/ or started on thionamides a few
days after their radiodine treatment.

2.

For patients with malignant disease

Treatment side effects may occur and are generally

dose-related. These include nausea and vomiting,
sialadenitis, xerostomia, neck swelling, and
cytopenia. These are rare with administered
activities below 7400 MBq (200 mCi). Hydration of
the patient with instructions urging frequent urination
for up to two weeks and efforts to increase salivary
flow may reduce radiation exposure to the bladder
and salivary glands. Antiemetics may be helpful.

D.

Radiopharmaceutical: I-131

E.

Radiation Dosimetry in Adults

Absorbed Dose Assuming No Thyroid Uptake

(Athyrotic)

ORGAN

mGy/MBq

Bladder wall

0.610

Lower colon wall

0.043

Kidneys

0.065

Ovaries

0.042

Testes

0.037

Stomach

0.034

ICRP 53 (page 253)

Absorbed Dose, Assuming 55% Thyroid Uptake and 20
gram gland (Hyperthyroid)
Organ
Thyroid
Bladder Wall
Breast
Upper colon wall
Ovaries
Testes

mGy/MBq
790
0.290
0.091
0.058
0.041
0.026

ICRP 53 (page 278) based on a 20g gland

Administered
131I Activity
MBq

Thyroid
Uptake
(%)

Radiation Dose to the Red Marrow*

mGy/MBq
Adult

74-7400 MBq

0
5
35
45
55

0.035
0.038
0.086
0.100
0.120

* dose may vary depending on the whole body effective half-life of I-131

ICRP53 pages 275-278

Child (10yrs)
0.065
0.070
0.160
0.190
0.220

1.

Calculation of administered 131I activity

a.

For thyrotoxicosis
The main aim of treatment should be to
prevent persisting or recurrent hyperthyroidism.
Since the incidence and rate of appearance
of hypothyroidism is directly related to the
delivered thyroid radiation dose, the optimal
dose calculation for treatment should be
based on measurements that permit the
delivery of a specified and planned radiation
bdose to the thyroid. This requires
measurement of thyroid uptake, gland size,
and an estimate of thyroidal turnover rate
(based upon several uptake measurements
over a period of one week). Many medical
centers find this method of calculating the
administered activity too onerous since it
requires that the patient return on several
occasions. As an alternative, most medical
centers assume a generic thyroidal turnover
rate. Many strategies have been proposed.
The approach used by each practice should
suit the practice setting.

i.

Some attempt to deliver a specific

amount of radiation to the thyroid gland
on the basis of 131I absorbed per gram
of gland. This generally ranges from 2.2
3.0 MBq/gm (60 80 uCi/gm) up to 6.07.0 MBq/gm (160-180 uCi/gm). As a
general rule, smaller administered

activities are associated with higher

rates of treatment failure and lower
rates of post-treatment hypothyroidism.

ii.

Some practices routinely deliver fixed

administered activity for all patients.
This may involve a small fixed amount
(74111 MBq or 23 mCi), repeated as
necessary, a large fixed amount
(370740 MBq or 10-20 mCi), or a sliding
scale, with the administered activity
based upon the size of the gland
and/or severity of thyrotoxicosis.

iii.

For patients with nodular

hyperthyroidism and for patients
receiving repeat therapy for prior
treatment failure, larger administered
activities are usually needed.

b.

For thyroid malignancy

i.

For patients undergoing ablation of

thyroid remnant, administered activities
in the range of 37005500 MBq (100150
mCi) are usually given.

ii.

For patients undergoing re-treatment for

residual disease or local recurrence,
somewhat larger administered activities

(in the range of 5550 MBq (150 mCi) are

often used.

iii.

For patients with distant metastases,

administered activities of 7400 MBq (200
mCi) or more may be used. Caution is
recommended in patients with diffuse
lung metastases in view of the potential
risk of radiation fibrosis.

c.

Patients should have a whole body scan

performed one to two weeks after treatment
for staging purposes.

F.

Sources of error

1.

For hyperthyroid patients

Sources of inaccuracy may occur in the thyroid

uptake, the estimated weight of the gland and in
unpredictable variations in effective half-life or
radiation sensitivity of the gland.

2.

For thyroid cancer

a.

If administered activities of 74 MBq (2.0 mCi)

or more of 131I were used for the whole body
iodine scan, stunning of the thyroid
remnant or residual disease could alter the
effectiveness of therapy.

b.

Some tumors may possess cells of different

radiosensitivity, which could predispose to
ultimate failure of therapy.

V.

ISSUES REQUIRING CLARIFICATION

A.

The role of recombinant TSH in treatment of patients still on

thyroid suppression.

B.

The use of 131 I whole body imaging prior to 131I therapy for
thyroid cancer
and whether stunning of the thyroid remnant occurs.

C.

The necessity of treating small (<1.5 cm.) papillary thyroid

cancers with 131i.

D.

Blind retreatment of 131I scan negative, thyroglobulin

positive patients.

VI.

CONCISE BIBLIOGRAPHY
1. Brill DR, Perez CA, at al. The American College of Radiology
Standard for the Performance of Therapy with Unsealed
Radionuclide Sources. American College of Radiology, 1996.

2. Barrington SF, Kettle AG, et al. Radiation dose rates from patients
receiving iodine-131 therapy for carcinoma of the thyroid. Eur J
Nucl Med 23: 123-30 (1996). Published erratum appears in Eur J
Nucl Med 1997: 24: 1545

3. Sparks RB, Siegel JA. The need for better methods to determine
release criteria for patients administered radioactive material.
Health Phys 1998: 75: 385-8.

4. MIRD Committee of Society of Nuclear Medicine. MIRD Dose

Estimate Report No. 5. J Nucl Med 1975; 16:587.

5. Stabin M, Stubbs J, Toohey R. Radiation Dose Estimates for

Radiopharmaceuticals 30 April 1996. Radiation Dose Internal
Information Center, Oak Ridge, TN.

6. Schlumberger MJ. Papillary and follicular thyroid carcinoma.

NEJM 1998: 338: 297-306.

7. Lerch H, Schober O, Kuwar T, et al. Survival of differentiated

thyroid carcinoma studied in 500 patients. J Clin Oncol 1997: 15:
2067-75

8. Mazzaferri EL, Robyn J. Post surgical management of

differentiated thyroid carcinoma. Otolaryngologic Clin N Amer
1996: 637-662

9. European Association of Nuclear Medicine.

Monograph [131-

I] Iodide. 1999.

10. International Committee on Radiation Protection (ICRP).

Publication 53. Pergamon Press. New York. 1987. 18 (275-8).

K. Zanzonico PB, Brill AB, Becker DV, et al. Radiation

Dosimetry: Chapter 9 p 106-134 in Principles of Nuclear
Medicine 1995 Ed. Wagner HN.

VI

DISCLAIMER

The European Association of Nuclear Medicine has written and

approved guidelines to promote the cost effective use of high quality
nuclear medicine therapeutic procedures. These generic
recommendations cannot be rigidly applied to all patients in all
practice settings. The guidelines should not be deemed inclusive of all
proper procedures or exclusive of other procedures reasonably
directed to obtaining the same results. Advances in medicine occur at
a rapid rate. The date of a guideline should always be considered in
determining its current applicability.

VII

DESCRIPTION OF THE GUIDELINE DEVELOPMENT PROCESS

The EANM Radionuclide Therapy Committee has been involved in the

process of guideline development for undertaking radionuclide
therapies since 1995. A multinational group of therapy experts
developed a series of monographs on the radioncuclide therapy
agents licensed for use throughout Europe. Subsequently a series of
protocols was published on the Internet for use by members of the
European Association of Nuclear Medicine. The monographs and
protocols were achieved through a process of consensus taking note
of the evidence available at the time of writing. The monographs and
protocols have been in the public domain for four years and
comments have been received from members of the nuclear
medicine community. The guidelines have been developed using
material within the monographs and protocols and have been
formatted to harmonise with the Society of Nuclear Medicine Therapy
Guidelines format.

Last amended:

14.02.2002