• Introduced by Seidlin et al. in 1946

• 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

• Most of the radiation dose is delivered by B-particles

• 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

• 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

• Picture of the capsule to be added

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:

peroxidaseI- I+

• Oxidized iodine can then be used in production of thyroid hormones.

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

• 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

Prerequisites

• TSH of >30mU/L is associated with increased RAI uptake in tumors

– withdrawal of LT-3 for 2 weeks, or– discontinuation of LT-4for 3 weeks– rhTSH stimulation

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 inhibitorsDemethylating agents

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)

• 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 WBSWBS- 2 mci used as a solution. Drink with straw.

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.

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).

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

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

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

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.

ATA guidelines

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.

• 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..

• 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>/=1.5cmMazzaferri EL et al: Thyroid remnant 131I ablation for papillary and follicular thyroid carcinoma; Thyroid. 1997 Apr;7(2):265-71

• 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.

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

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.

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

• 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

• Preablation radionuclide scan technetium-99m 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

• 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

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

• 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

Results

• 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

• 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)

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

Meta Analysis

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.

• 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.

• 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

• 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

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.

• Three approaches to 131I therapy:– empiric fixed amounts,– therapy determined by the upper bound limit of

blood and body dosimetry and – quantitative tumor dosimetry

Indications of RAI therapy

• Inoperable tumour• Postoperative gross residual disease, • Extrathyroidal spread, • Locoregional spread to the nodes• Distant metastasis

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

Cervical nodes• Fixed dose format – 150 mci – upto 200• Quantitative dosimetry Pulmonary metastasisSkeletal metastasis

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

Side effects

• Immediate• Delayed

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.

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