1) Radioiodine treatment (RAI) utilizes the ability of thyroid cancer cells to absorb iodine to effectively treat well-differentiated thyroid cancer. However, less differentiated cancers may not absorb iodine and become resistant to RAI treatment. 2) The document discusses the physics and physiology of radioactive iodine treatment, factors that influence treatment effectiveness like stunning, and guidelines around patient preparation and follow up including dosimetry approaches and activity levels for treatment. 3) Optimal RAI treatment requires differentiating cancer cells to absorb sufficient iodine doses without exceeding radiation safety limits, and the document discusses approaches and considerations for individualizing safe and effective treatment.

1. RADIOIODINE IN THYROID
MALIGNANCY

2. PHYSIOLOGY

3. • The predominant excretion of iodine is through the urinary route,
although a fraction is excreted through feces and other body fluids like
sweat and saliva.
• The fetal thyroid starts concentrating iodine at 12 weeks of gestation,
which causes RAI treatment to be a contraindication in pregnancy

4. • The ability of the well-differentiated thyroid cancer cells to absorb
iodine through the sodium-iodide symporter makes RAI an effective
treatment.
• As the cancer cells become undifferentiated, they lose the NIS
expression, hence do not take up RAI and do not respond to RAI
treatment.
• The glucose metabolism of poorly differentiated (PD) cancers is high,
so fluorine-18 fluorodeoxyglucose (F-18 FDG) PET might detect the
PD cancer lesions.

5. NUCLEAR PHYSICS OF RADIOACTIVE IODINE

6. I131
• Neutron irradiation of Tellurium 130 or fission product of Uranium 235
• Biological half life 8.04 days
• Radio decay Emission – 90% beta radiation, 10% gamma radiation.Hence poor resolution in Gamma cameras. Beta
rays destroy thyroid cells.
• Tissue penetration of 0.6 to 2 mm.
• The predominant gamma emission of I-131 is the 364 KeV high-energy photons, which causes radiation exposure
concerns to the public.
• Gamma radiation is also used in imaging biodistribution.
• I 123 – 84% gamma emission which can be utilized in diagnostic studies rather than therapeutics

7. ROLE OF RADIO-IODINE
• Diagnostic – I-123, I-125 and I-131 through Gamma emission
• Therapeutic roles :Rem
REMNANT ABLATION - Follow up with Post operative Tg and WBS
Adjuvant treatment
ADJUVANT THERAPY - Improve DFS in patients with high risk of recurrence
Therapeutic ablation
Improve DFS and DSS by treating persistent disease

8. WHEN TO OPT RAI
• Post operative thyroglobulin levels
• Post surgery risk stratification based on ATA guidelines

9. THYROGLOBULIN
• Direct Predictor of thyroid remnant post surgery
• Thyroglobulin levels reach almost traces by 3 to 4 weeks postoperatively
• TSH stimulated Tg < 1ng/mL - No evidence of disease
• When Unstimulated Thyroglobulin levels > 5-10ng/mL – increased chance of thyroid remnant and metastasis
detection on post-ablation scan

10. WHEN TO ADMINISTER THERAPEUTIC DOSE
• Several studies mention Remnant ablation failure if given in doses more than 3 mCi and delay in
therapeutic dose for more than 1 week.
• When performed, pretherapy diagnostic scans should utilize I-123 (1.5–3 mCi) or a low activity of I-131
(1–3 mCi), with the therapeutic dose administered within 72 hours of the diagnostic activity

11. ROLE OF PREABLATION WHOLE BODY SCAN

12. STUNNING
• First described by Rawson et al., in 1951
• Thyroid stunning refers to decreased uptake of a therapeutic
radioiodine dose by remnant thyroid tissue or by functioning
metastasis in a post-treatment whole-body scan because of a
preceding dose of radioiodine given for a diagnostic scan.
• The frequency of stunning was 40%, 67%, and 89% after 3, 5, and 10
mCi respectively

13. STUNNING ON THE OUTCOME OF ABLATION
• Park et al. success rate of ablation after 131 scans 56% vs after I-123
scans 72%
• Muratet et al. Success rate of ablation after 3 mCi is 50% vs after 1
mCi of I-131 (76%, p < 0.001).
• Even 1 mCi of I-131 caused stunning in a few cases

15. 2015 ATA guidelines expanded inclusion criteria

20. PRE-ABLATION PREPARATION
• Thyroid Hormone withdrawal or Recombinant human TSH (Thyrogen)
• Goal TSH of >30mIU/L is necessary
• Thyroxine withdrawn for 3 to 4 weeks, in case of T3 withdrawal of 1
to 2 weeks is sufficient

22. Low iodine diet
• Plujimen et al found a significantly higher ablation rate in patients
performing a 2-week Low Iodine Diet compared to the control group (65%
vs 48%).
• Withhold iodine-containing vitamin supplementation for 1–2 weeks
prior to 131I.
• Normal diet to be resumed on administration of 131I.
• Routine urinary iodine concentration (UIC)/urine spot iodine
measurement to ensure LID compliance is not recommended.

23. THYROGEN
• Two dose regimen
• 0.9mg/m
• 2nd dose - 24 hours later
• Route of administration - IM, buttock
• Oral RAI can be given 24 hours after 2nd injection
• Cost in India (4000 to 12000)

24. I-131 Administration
• Oral liquid or capsule
• Diagnostic – Outpatient basis
• Ablation – Inpatient basis

25. PRINCIPLE OF ACHIEVING LOW DOSE ABLATION
• Although harm from radiation exposure to personal contacts of 131I-
treated patients has not been shown, these recommendations follow
principle of reducing radiation exposure to levels that are As Low As
Reasonably Achievable (ALARA).
• Inherent within ALARA is an acknowledgement that even unapparent
injuries are cumulative, and over time, small effects contribute to
risks.

28. ISOLATION ROOM

29. Delay RAI ablation..
(i)Pregnancy is an absolute contraindication to RAI and must be excluded by human chorionic
gonadotropin (hCG) test within 48 h of RAI administration.
(ii)Breastfeeding and lactation must be discontinued at least 8 weeks prior to RAI and not resumed
until after a subsequent pregnancy.
(iii)Following administration of iodinated radiology contrast media, a minimum interval of 8 weeks
is recommended prior to RAI ablation or therapy, but this can be reduced to 4 weeks if clinical
circumstances dictate earlier treatment (providing estimated eGFR is normal).
(iv)If diagnostic whole-body scintigraphy (DxWBS) is performed prior to RAI ablation or therapy, 123I
(or 124I) is preferable, but 131I can be utilised provided activity is <400 MBq to minimise risk of
stunning. This is not routinely recommended and should be considered investigational.
(v)Consider withholding amiodarone for 12 months prior to RAI ablation or therapy, if clinically
appropriate.

30. Individualised Discharge Advice
• Serial measurements of external dose rate or residual activity should
be used to guide time of discharge and to aid individualised radiation
protection advice.
• Patients can be considered for discharge when the residual activity
falls below 800 MBq or the external dose rate falls below 40 μSv/h at
1 m.
• For contact restrictions, patients receiving ablative doses, only rarely
are these likely to exceed 7 days post-administration.
• For patients receiving a therapeutic dose, in a minority of cases
restrictions may extend for a longer period, but are unlikely to
exceed 14 days.

31. DISCHARGE SAFETY LEVELS
The dose rate - measured using hand-held, calibrated dose-rate
meter.
The following dose-rate thresholds (at 1 m) were used for discharge,
and the subsequent lifting of restrictions:
Discharge using private transport = 40 μSv/h
Discharge using public transport = 20 μSv/h
End of contact restriction with adults and older children = 7.5 μSv/h
End of contact restriction with pregnant women and younger children = 1.5
μSv/h

33. RAI on DSS or Overall Survival
• Not associated with improved DSS or Overall survival in Very low risk and Low risk DTC patients
• Obvious and significant benefit of RRA is noted in high risk DTC patients

34. DISEASE FREE STATUS
• No clinical evidence of tumor
• No imaging evidence of tumor by RAI imaging
• Low serum Tg levels during TSH suppression (Tg <0.2 ng/mL) or after stimulation (Tg <1 ng/mL) in the
absence of interfering antibodies

35. ADJUVANT THERAPY
• Treat suspected microscopic residual disease in absence of known distant metastases
• Administered activities above those used for remnant ablation up to 150mCi

36. POST THERAPY WBS
• Done 3 to 7 days after Ablative therapy
• Can additionally detect distant metastases not seen in Dx-WBS in 10 to 13% of patients

37. FOLLOW UP WBS
• Low-risk and intermediate-risk patients (lower risk features) with an undetectable Tg on thyroid
hormone with negative anti-Tg antibodies and a negative US (excellent response to therapy) do not
require routine diagnostic WBS during follow-up.
• Diagnostic WBS, 6–12 months after adjuvant RAI therapy can be useful in the follow-up of patients
with high or intermediate risk (higher risk features) of persistent disease and should be done with
I-123 or low activity I-131.

38. LUNG METASTASIS
Micro metastases
– <2mm, not seen on anatomic
imaging
– Rates of complete remission
higher
– RAI is repeated every 6 months as
long as
disease concentrates RAI
Macro metastases
– RAI is preferred initially
– Risk of pulmonary fibrosis is higher
– Repeated only if there is reduction in size
and
Thyroglobulin levels.

39. BONE METASTASIS
• RAI therapy of iodine-avid bone metastases has been associated with improved survival although RAI is
rarely curative.
• The RAI activity administered can be given empirically (100–200 mCi) or determined by dosimetry.

40. TENIS SYNDROME
• Thyroglobulin Elevated Negative Iodine Scintigraphy
• 10 to 15% of patients (Tg elevation, Negative IS)
• Do CxR, Neck USG, CT or MRI, Bone scan
If all scans are negative, then
• Decision of Empirical RAI therapy
• Based on PET/CT
• If PET CT is negative – proceed with Empirical RAI

41. OPTIMAL DOSAGE OF I-131
Repeated sub therapeutic doses of I-131 might induce
dedifferentiation and a loss of tumor iodine-concentrating ability.
METHODS
■ Fixed dose method
■ Lesion based dosimetry
■ Maximal safe dose method

42. Fixed dose method
Depends on Disease extent
• 100 – 175mCi for cervical nodal metastases
• 150 – 200 mCi for Distant metastases
• Maxon et al. patients with metastases that persisted after I-131 therapy received
significantly lower radiation doses per millicurie of administered I-131, suggesting need
for dosimetric approach

43. LESION BASED DOSIMETRY
• I 131 dose
• Co – Initial concentration of I 131 in lesion
• T1/2 – effective half life activity inside that lesion
DOSE(cGy) - 5 x 0.63 x Co x T1/2

44. MAXIMAL SAFE DOSE METHOD
According to MSKCC, I-131 dose should not
• Exceed 2 gy in blood
• Result in a body retention of 120 mci at 48 h
• Result in lung retention of 80 mci at 48 h in cases of diffuse pulmonary
metastasis

45. RAI – REFRACTORY TO RX
• Malignant/metastatic tissue does not concentrate RAI
• Tumor tissue loses the ability to concentrate RAI after previous evidence of RAI-avid disease
• Metastatic disease progresses despite significant concentration of RAI.

48. THANK YOU