This document discusses the use of radioactive iodine (131I) for diagnosis and treatment of thyroid cancer. Some key points: - 131I localizes in thyroid tissue and can be used to ablate thyroid remnants after surgery or treat thyroid cancer metastases. It emits beta and gamma radiation. - For remnant ablation, lower doses (30-100 mCi) are usually sufficient while higher doses (100-200 mCi) may be needed for more aggressive cancers. Success rates are similar between low vs high doses and thyroid hormone withdrawal vs rhTSH. - Post-therapy scans 2-10 days after treatment can identify additional metastases not seen on diagnostic scans in 10-26% of

2. • Introduced by Seidlin et al. in 1946

3. • Physical half-life of 131I is 8.02 d.
• Mainly emit B rays– 90% of radioactivity of
131I, (and Gama rays)
• 131I is available for oral ingestion as sodium
iodine

4. • Most of the radiation dose is delivered by Bparticles
• B-particles do not penetrate deep into tissue(2
mm in depth, at most)
• Gama-radiation contributes only 10% of the total
radiation dose, fraction of gama-rays –absorbed
by functioning tyhroid tissue and vast majority
leaving via skin surface-Detected by a radiation
detector

5. • As liquid solution or in capsules.
• Each capsule accounts for 50 micro curie
• Capsules safer than liquid- less radioactivity
released into air during handling.
• Also result in less oral mucosal irritation
• Simultaneous ingestion large amounts of water
attenuates radiation dose emitted to gastric wall
• Rapidly and completely absorbed in the upper
intestine

6. • Picture of the capsule to be added

7. Iodine Metabolism
• Dietary iodine is absorbed in the GI tract, then taken
up by the thyroid gland (or removed from the body
by the kidneys).
• The transport of iodide into follicular cells is
dependent upon a Na+/I- cotransport system.
• Iodide taken up by the thyroid gland is oxidized by
peroxide in the lumen of the follicle:
peroxidase
I-
I+
• Oxidized iodine can then be used in production of
thyroid hormones.

9. Cancer vs normal cells
• Metabolism of radioiodine in papillary and
follicular carcinoma is profoundly altered when
compared with normal thyroid tissue.
• Several defects are present in cancer tissue:
– iodine uptake, via the sodium-iodide symporter (NIS),
is always decreased and is undetectable in about a
third of patients;
– Iodine organification is markedly reduced;
– Effective half-life of iodine in tumor tissue is always
shorter

10. • Tissues that often take up iodine and can be
misconstrued as metastases include the
– salivary glands in the mouth,
– esophagus (as a result of swallowing radioactive
saliva),
– thymus gland,
– breasts in some women,
– liver, stomach, colon, bladder

11. Prerequisites
• TSH of >30mU/L is associated with increased
RAI uptake in tumors
– withdrawal of LT-3for 2 weeks, or
– discontinuation of LT-4for 3 weeks
– rhTSH stimulation

12. Enhancing radioiodine uptake
• Low iodine diet
• Lithium - 10 mg/kg/day for 7 days. To keep S. Lithium levels at
0.8-1.2 mmol/L)
– Lithium had been shown to reduce exit of iodine from
normal thyroid cells
• Retinoic acid (1.2 mg/kg/day) – retinoids -apparently
redifferentiate thyroid cancer cells - enhanced
radioiodine uptake
Other agents:
• Based on increasing NIS expression in thyroid cancer cells
Histone deacetylate inhibitors
Demethylating agents

13. To be avoided
• FOOD SUPPPLEMENTS
• Iodised salt/Salty food-potato chips,nuts
• Sea food
•
•
•
•
DRUGS
1)iodex
2)amiodarone
3)Contrast medias(avoid CT scans)

14. • Post operative diagnostic I 131 scan –
– Doses less than 5 mCi – unlikely to miss out
treatable foci of disease
– Large dose causes stunning
We use 50 micro curie 131I(one capsule orally)
Do the neck uptake scan using a rectilinear scan.
If uptake <4% - proceed with WBS
WBS- 2 mci used as a solution. Drink with straw.

15. Stunning effect
• Stunning is defined as a reduction in uptake of
the 131I therapy dose induced by a
pretreatment diagnostic activity.
• Occurs most prominently with higher activities
(5–10 mCi) of 131I ,with increasing time
between the diagnostic dose and therapy
• Does not occur if the treatment dose is given
within 72 hours of the scanning dose.

16. ATA guidelines
• Based on Risk stratification of individual
patient,
• The primary goal of the first dose of RAI after
total thyroidectomy may be
– Remnant ablation (to facilitate detection of
recurrent disease and initial staging),
– Adjuvant therapy (to decrease risk of recurrence
and disease specific mortality by destroying
suspected, but unproven metastatic disease)
– RAI therapy (to treat known persistent disease).

17. Radio iodine abalation
Ablation of small amount of residual normal thyroid
remaining after surgery, left behind inadverently
or deliberately
May facilitate the
– early detection of recurrence based on serum Tg
– RAI WBS

18. ATA recommendations
• RAI ablation is recommended for all patients
with
– known distant metastases,
– gross extrathyroidal extension of the tumor
regardless of tumor size, or
– Primary tumor size >4 cm even in the absence of
other higher risk features

19. ATA recommendations
• RAI ablation is recommended for selected
patients with
– 1–4cm thyroid cancers confined to the thyroid,
– have documented lymph node metastases,
– other higher risk features( combination of age, tumor size, lymph
node status, and individual histology predicts an intermediate to high risk
of recurrence or death)
• histologic subtypes (such as tall cell, columnar, insular,
and solid variants, as well as poorly differentiated
thyroid cancer),
• the presence of intrathyroidal vascular invasion,
• the finding of gross or microscopic multifocal disease

20. ATA recommendations
• RAI ablation is not recommended for patients
with unifocal cancer <1 cm without other
higher risk features.
• RAI ablation is not recommended for patients
with multifocal cancer when all foci are <1 cm
in the absence other higher risk features.

21. ATA guidelines

22. MD anderson experience
• 1599 patient outcome analysis for various
treatment for differentiated thyroid Ca
• 46% had radioiodine therapy
• Treatment with radioiodine was the single most
powerful prognostic indicator for increased DFS
(p< 0.001)
• Its use significantly increased the survival both
low and high risk group
• Adult patients , females with intrathyroidal
papillary carcinoma treated with TT + RAI
between 20-59yrs – best prognosis
J Clin Endocrinol Metab. 1992 Sep;75(3):714-20.

23. • Decision analytic model -examine whether
apparently localized thyroid carcinoma pts
should receive RAI
– RAI modestly improves life expectancy by 2 to 15
months.
– benefit of reduction in likelihood of recurrence
outweighs risk of leukemia.
Wong et al ,Endocrinol Metab Clin North Am. 1990 Sep;19(3):741-60
Ablative radioactive iodine therapy for apparently localized thyroid
carcinoma,Massachusetts..

24. • 1004 dtc- Followed up with
– RAI – 151
– thyroid hormone alone 755
– no postoperative medical therapy -98
Tumor recurrence ~ threefold lower p < 0.001in RAI vs
other treatment
Fewer patients developed distant metastases (p < 0.002)
Significantly more pronounced in t>/=1.5cm
Mazzaferri EL et al: Thyroid remnant 131I ablation for papillary and
follicular thyroid carcinoma; Thyroid. 1997 Apr;7(2):265-71

25. • Methods of abalation
– Low dose – 30mCi
– 0-92% complete abalation.
Adv:Low cost, Reduced radiation exposure
– High dose – 80-150mCi
– Given as inpatient therapy
– Calculated dose abalation
– Individualised treatment- not a standard dose of
RAI but a standard dose of radiation to the bed.

26. National Thyroid Cancer Treatment Cooperative
Study Group (NTCTCSG)
• 2936 patients , median follow-up of 3years
• Near-total thyroidectomy followed by RAI therapy
and aggressive thyroid hormone suppression
therapy predicted improved overall survival of
patients with NTCTCSG stage III and IV disease
• Also beneficial for patients with NTCTCSG stage II
disease
• No impact of therapy was observed in patients
with stage I disease

28. Mayo clinic experience
• Review of more than 2,500 patients at the Mayo
Clinic between 1940 and 2000 having under gone
surgery and RRA
• RRA did not significantly improve the outcome
(either Cause specific mortality or Tumour
Reccurence ) in low-risk (MACIS < 6) patients
previously treated with initial near-total or total
thyroidectomy
• They discouraged the routine use of RRA in such
patients.

29. HiLo trial
• Multicentric study in UK
– Comparing low dose vs high dose radio iodine
– Thyrotropin alpha vs thyroid hormone withdrawal
• Inclusion Criteria
– stage T1 to T3N0/N+ but no distant metastasis
– total thyroidectomy, with or without central
lymph-node dissection

30. • 4 arms
– low-dose(220) or high-dose radioiodine(218),
– each combined with thyrotropin alfa (219)or
thyroid hormone withdrawal(219).
Thyroid hormone withdrawal, thyroxine was
discontinued 4 weeks before ablation
Thyrotropin alfa-intramuscular injection (0.9
mg)x2days prior to scan

32. • Preablation radionuclide scan technetium99m pertechnetate IV-to assess remnant size
• Whole-body iodine-131 scan- performed 3 to
7 days after ablation -gamma camera
• Diagnostic whole-body scan- performed 6 to 9
months after ablation – with iodine-131

33. • Primary end point
– success rate for ablation -defined as both a
negative scan (<0.1% uptake over the thyroid bed)
and a thyroglobulin level of less than 2.0 ng per
milliliter at 6 to 9 months.
– One of these criteria used if other not available
• Secondary end points
– were the number of days of hospitalization;
adverse events during ablation and 3 months after
ablation

34. Results
• Ablation was successful in
– 182 / 214 patients (85.0%) in low-dose radioiodine vs
– 184 / 207 patients (88.9%) in the high dose groups
• The difference in the success rate for this
comparison was
– −2.7 percentage points on the basis of scanning
results alone and
– −3.8 percentage points on the basis of both scanning
results and thyroglobulin level

35. Results
• Success rates were also similar in thyrotropin
alfa vs thyroid hormone withdrawal successful ablation
– 183 of 210 patients (87.1%) in the thyrotropin
alfa group versus
– 183 of 211 patients (86.7%) in the group
undergoing thyroid hormone withdrawal

36. • The treatment effects for stage T3 tumors or
lymph-node involvement were consistent with
those for all patients.
• −0.7 percentage points for patients with stage
T3 tumors and 4.9 percentage points for those
with lymph-node involvement

37. • Adverse events were 21% in the low-dose
group versus 33% in the high-dose group
(P=0.007)
• More patients in the high-dose group than in
the low-dose group were hospitalized for at
least 3 days (36.3% vs. 13.0%, P<0.001)

38. Draw backs
• Exclusion criteria
– the presence of aggressive malignant variants,
including tall-cell, insular, poorly differentiated,
and diffuse sclerosing thyroid cancer
• Results relate to ablation success at 6 to 9
months and do not address future recurrences

39. Meta Analysis

40. ATA recommendations
• The minimum activity (30–100 mCi) necessary
to achieve successful remnant ablation should
be utilized, particularly for low-risk patients.
• If residual microscopic disease is suspected or
documented, or if there is a more aggressive
tumor histology (e.g., tall cell, insular,
columnar cell carcinoma), then higher
activities(100–200 mCi) may be appropriate.

41. • A posttherapy scan is recommended following
RAI remnant ablation - typically done 2–10
days after therapeutic dose is administered
• Additional metastatic foci have been reported
in 10–26% of patients scanned following high
dose RAI treatment compared with the
diagnostic scan.

42. • Disease not visualized on DxWBS, regardless of
the activity of 131I employed, may occasionally
be visualized on RxWBS images.
• Following RAI ablation, when the posttherapy
scan does not reveal uptake outside the thyroid
bed, subsequent DxWBS have low sensitivity and
are usually not necessary in low-risk patients who
are clinically free of residual tumor and have an
undetectable serum Tg

43. • Post 1st RxWBS(post RAI), low-risk patients
with an undetectable Tg on thyroid hormone
with no Anti Tg antibodies , negative US do
not require routine DxWBS during follow-up

44. Radio iodine therapy
• For regional nodal metastases discovered on
DxWBS
• Surgery is typically used in the presence of bulky
disease and amenable to surgery on anatomic
imaging
• RAI may be employed –adjunctively following
surgery for regional nodal disease or aero
digestive invasion if residual RAI avid disease is
present or suspected.

45. • Three approaches to 131I therapy:
– empiric fixed amounts,
– therapy determined by the upper bound limit of
blood and body dosimetry and
– quantitative tumor dosimetry

46. Indications of RAI therapy
•
•
•
•
•
Inoperable tumour
Postoperative gross residual disease,
Extrathyroidal spread,
Locoregional spread to the nodes
Distant metastasis

47. • Max safe dose: <200 to blood
• Retained not more than 120mCi-whole body 48hrs

48. Cervical nodes
• Fixed dose format – 150 mci – upto 200
• Quantitative dosimetry
Pulmonary metastasis
Skeletal metastasis

49. • The most common distant metastatic sites are
lungs, spine, and appendicular bone.

50. Side effects
• Immediate
• Delayed

51. Immediate:
1)Neck swelling/edema 24-48 hrs
• More if there is substantial mass of thyroid
left behind
• Responds well to steroids
• Rarely may need tracheostomy, may develop
thyroid storm.
2) Sialadenitis –plenty of water, lemon.

52. Side effects
• Nausea, Loss of taste or dysgeusia- often last
few days
• Sialadenitis-pain and enlargement of salivary
glands, rarely progress to chronic xerostomia
– Prophylaxis -ingestion of large quantities of fluids
sialogogues- lemon juice or chewing gum
• Teratogenicity - recommended that
conception be delayed for 1 y after
therapeutic administrations of I131