Radionuclide Therapy by Stephen M. Karesh, Ph.D. Nuclear Medicine Department

1. Radionuclide Therapy by Stephen M. Karesh, Ph.D. Nuclear Medicine Department Loyola University Medical Center

2. Types of Therapy Performed in Hospitals Radiopharmaceutical Therapy Brachytherapy Teletherapy

3. Therapeutic Radiopharmaceutical a radioactive drug which, when used for therapeutic purposes, typically elicits no physiological response from the patient.

4. Characteristics of the Ideal Therapeutic Radiopharmaceutical 1. Moderately long teff (measured in days). For 131I NaI, teff in thyroid = 6 d 2. Prefer b- particle emitters (high LET) to maximize tissue dose/mCi injected. 3. Prefer high energy (>1 MeV) 4. Must have high target:non-target ratio to minimize radiation dose to non-target organs 5. Prefer rapid excretion of unbound material. 6. Readily available, inexpensive 7. Minimal radiation exposure to personnel in contact with patient, i.e., 32P

5. Radionuclide Therapy Types of Emissions Used for Therapy alpha particles beta- particles electrons gamma rays X-rays

6. Radionuclide Therapy Radioisotopes Used for Therapy I-131 for treatment of thyroid diseases P-32 for treatment of polycythemia vera P-32, Sr-89, Sm-153, Re-186 for palliation of pain from bony metastases Dy-165, Ho-166 for radiation synovectomy

7. Group IV Radiopharmaceuticals Includes all prepared therapeutic radiopharmaceuticals whose use does not require hospitalization for purposes of radiation safety.

8. Examples of Group IV Radiopharmaceuticals 1. 131I NaI for treatment of hyperthyroidism 2. 32P as soluble sodium phosphate for treatment of polycythemia vera 3. 32P as insoluble chromic phosphate colloid for intracavitary treatment of malignant effusions. 4. 89Sr as soluble SrCl2 for palliation of pain in patients with metastatic breast or prostate cancer. 5. Any investigational therapeutic radiopharmaceutical not requiring hospitalization for purposes of radiation safety.

9. Group V Radiopharmaceuticals Includes all therapeutic radiopharmaceuticals that require hospitalization for purposes of radiation safety.

10. Examples of Group V Radiopharmaceuticals 1. 131I NaI for treatment of thyroid Ca 2. 198Au for intracavitary treatment of malignant effusions 3. Any investigational therapeutic radiopharmaceutical requiring hospitalization for purposes of radiation safety.

11. Group VI Radiopharmaceuticals Includes sources and devices containing byproduct material that are used for therapeutic applications.

12. Examples of Group VI Radiopharmaceuticals 1. 241Am as a sealed source in a bone mineral analyzer 2. 137Cs encased in needles and applicator cells for topical, interstitial, and intracavitary treatment of cancer 3. 60Co encased in needles and applicator cells for topical, interstitial, and intracavitary treatment of cancer 4. 198Au seeds for interstitial treatment of Ca

13. Group VI Radiopharmaceuticals 5. 125I as a sealed source in a bone mineral analyzer 6. 128Ir as seeds encased in nylon ribbon for interstitial treatment of cancer 7. 90Sr sealed in an applicator for treatment of superficial eye conditions 8. 125I as seeds for interstitial treatment of cancer

14. Thyroid Diseases Treatable with 131I-NaI - hyperthyroidism (Graves disease) - toxic nodular goiter (Plummer’s disease) - thyroid carcinoma (ranked in order of likelihood of 131I uptake) 1. Follicular 2. Papillary the other two types of thyroid cancer, medullary and anaplastic, are not treatable with I-131

15. Decay Scheme of I-131 131 I 53 1 2 3 4  5 6 0.7229 0.6670 0.6370 0.4048 0.3644 0.3412 0.1539 0.0801 0.00 14 13 12 11 8 7 5 3 10 9 6 4 2 1 131 Stable Xe 54

16. Quiz This decay scheme indicates that there are 14 gammas and 6 betas emitted from I-131. Therefore, True or False, 14/20 of the tissue damage is attributable to gammas and 6/20 to betas.

17. Answer False for 2 reasons: 1. The LET (Linear Transfer Rate) for betas is much higher than for gammas; consequently they confer a much higher radiation dose 2. The fractions 14/20 and 6/20 imply that the % abundance of each of these 20 emissions is exactly 5%, which is not possible. In fact the % abundances vary from a fraction of 1% to almost 85%. Correct answer is that ~90% of tissue damage is attributable to beta particles.

18. Typical Doses of 131I Compounds route of proceduredose (mCi)administration raiu, normal 0.005 oral raiu & scan, substernal 0.100 oral total body mets survey 5-10 oral hyperthyroidism 5-15 oral toxic nodular goiter 25 oral thyroid Ca therapy 75-225 oral

19. Radiation Dosimetry of 131I- NaI following oral administration of 10 mCi dose of 131I-NaI for treatment of hyperthyroidism, 90% of dose to tissue is achieved by b- emissions. For a hyperthyroid patient treated with I-131: absorbed radiation dose Tissue(rads/10 mCi of I-131) Thyroid 11,000. Testes 9.2 Ovaries 9.3 Whole body 16.0

20. Dose Determination for Therapy in Graves Disease Method 1 Measure % uptake; estimate mass of thyroid (g) Dose = 60-100 mCi/g x mass (g) x 100% % uptake disadvantage: since 60-100 mCi /g is a wide range, it is difficult to determine the appropriate factor for an individual patient. Use of this formula often results in incorrect estimate of the required dose, resulting in over- or under-dosing of patient.

21. Dose Determination for Therapy in Graves Disease Method 2 A standard dose of 131I NaI is given orally to all patients (8 mCi to females, 10 mCi to males) Advantage: adequately treats 85% of all Graves disease patients with 1 treatment. Disadvantage: of the 15% who are refractory, 10% require a second administration of 131I; the other 5% require a third dose of 131I.

22. Response of hyperthyroid patients to treatment with 131I sodium iodide day of administration no immediate effect 4-6 weeks patient begins to notice beneficial effects 12 weeks maximum beneficial effects observed 6 months few observable changes after this interval

23. Long-term Side Effect As indicated in the following graph, the rate of hypothyroidism after the first year is 3%/year for all patients treated with 131I sodium iodide for Graves disease. They are treated with synthroid daily for the rest of their lives.

24. Rate of Induction of Hypothyroidism Following Therapy with 131I-NaI 35 30 25 20 15 10 5 % hypothyroid 0 1 2 3 4 5 6 7 8 9 10 years post therapy with 131I-NaI

25. Precautions to be Observed with High-dose I-131 Therapy Patient 1. Keep your distance to minimize personal radiation dose 2. Patient is assigned a private room 3. Everyone involved with patient must wear film badge 4. Gloves must be used by patient to handle telephone, bed controls

26. Precautions to be Observed with High-dose I-131 Therapy Patient 5. Housekeeping not allowed in room until room is released by RSO 6. No visitors allowed for at least 24 hr 7. No bed baths 8. Patient must stay in bed unless instructed otherwise

27. Precautions to be Observed with High-dose I-131 Therapy Patient 9. Absorbent pads taped to floor from toilet to bed 10. Patient must use disposable items for food service 11. Diagnostic blood samples taken by Nuclear Medicine

28. Precautions to be Observed with High-dose I-131 Therapy Patient 12. If patient dies, attending physician must be notified immediately 13. Room must be surveyed by RSO prior to release for next use. 14. Every participant in therapy must have thyroid counted 24 hr post dose

29. Patient Release Criteria Reading <5 mR/hr at 1 meter from patient’s chest, which is equivalent to a body burden <30 mCi of I-131.

30. 89Sr strontium chloride Therapy for Palliation of Bony Metastases

31. Physical Characteristics of 89Sr prepared by 88Sr(n,g)89Sr t1/2 = 50.5 days type of decay: b- maximum energy: 1.463 MeV, 100% range of b- in tissue: 8 mm

32. Advances in Cancer Therapy Longer survival in many cancers Better pain control medication More aggressive radiotherapy End result: More people living with bone pain.

33. Bony Metastases inBreast and Prostate Cancer Prostate cancer 50% of patients have bone disease at time of diagnosis Breast cancer 15% of stage III patients and 50% of Stage IV patients have bone metastases

34. Therapeutic Approaches to Bone Pain NSAIDs Chemotherapy Hormonal Therapy External Beam Radiation Narcotic Therapy Radiopharmaceutical Therapy

35. Historical Approach to Radionuclide Therapy Na332PO4 in 1940’s 89SrCl2 in late 1980’s 153Sm EDTMP in late 1990’s

36. 32P-Na3PO4 1. long history 2. 60-75% response rate in literature 3. significant marrow depression- end point is toxicity 4. infrequently used

37. 89Sr strontium chloride therapy for palliation of bony metastases 1. Indications: bone pain caused byany primary malignancy metastatic to bone. Implication: Must have a bone scan positive for metastases. Most commonly used for breast and prostate cancer 2. Palliative, not curative 3. Bone localizer; calcium analog with distribution very similar to 99mTc-MDP

38. 89Sr Strontium Chloride Therapy for Palliation of Bony Metastases 4. 80% Response rate overall 5. Ratio of metastatic lesions to normal bone = 5:1 6. Ratio of metastatic lesions to marrow = 10:1 7. Retention of 89Sr in metastases longer than in bone

39. 89Sr Strontium Chloride Therapy for Palliation of Bony Metastases 8. No reported adverse reactions 9. 30-50% of patients have measurable decrease in WBC and platelets 10. Recovery begins at about 6 weeks 11. Flare phenomenon often prognostic indicator of successful treatment

40. Typical Dose: 89Sr chloride 4 mCi given by IV Injection for intractable bone pain from prostate, breast cancer or other primary malignancy

41. Radiation dosimetry of 89Sr chloride organrad/mCi red marrow 80.0 bladder wall 0.5 whole body 6.0

42. 89SrCl2 Therapy: Clinical Outcomes 80% response divided into 3 groups: moderate response morphine codeine marked response morphine advil dramatic response morphine no meds

43. Typical Administered Doses for 32P Compounds polycythemia vera soluble 32P Na3PO4 3-5 mCi IV injection malignant effusions colloidal 32P CrPO4 8-12 mCi intracavitary injection

44. 32P Na phosphate for treatment of p. vera 1. IV injection of 3-4 mCi for initial treatment, which adequately treats 50% of patients. 2. Of 50% requiring 2nd injection, 35% are successfully treated. Remainder are refractory to treatment and may require 3rd or 4th dose. 3. Median survival time for untreated patients after time of diagnosis is 1.5 yr. After treatment with 32PNa phosphate, interval is increased to 12 yr. 4. 11% incidence of leukemia in successfully treated patients.

45. 32P Na phosphate for treatment of polycythemia vera Controversy Is 11% incidence of leukemia a result of injection of 32P Na phosphate or is P. Vera a preleukemogenic condition whose natural course is development of leukemia? The increased risk of leukemia is probably partially attributable to both causes.

46. Radiation dosimetry following IV injection of 4 mCi of 32P Na phosphate. organabsorbed dose (rads) skeleton 240 liver 24 spleen 29 gonads 4 whole body 40

47. 32P chromic phosphate colloid for palliation of malignant effusions 1. Intracavitary injection: 10 mCi in 250 ml saline 2. >90% of patients respond => significantly decreased frequency of "tapping" required to remove fluid. 3. Rarely need to retreat patient. 4. Palliative, not curative. 5. Approved drug, <$1000 per treatment