Transcript No Slide Title
Radionuclide Therapy by Stephen M. Karesh, Ph.D.
Nuclear Medicine Department Loyola University Medical Center
Types of Therapy Performed in Hospitals
Radiopharmaceutical Therapy Brachytherapy Teletherapy
Therapeutic Radiopharmaceutical a radioactive drug which, when used for therapeutic purposes, typically elicits no physiological response from the patient.
Characteristics of the Ideal Therapeutic Radiopharmaceutical 1. Moderately long t eff (measured in days). For 131 I NaI, t eff 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., 32 P
Radionuclide Therapy
Types of Emissions Used for Therapy alpha particles beta- particles electrons gamma rays X-rays
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
Group IV Radiopharmaceuticals Includes all prepared therapeutic radiopharmaceuticals whose use does not require hospitalization for purposes of radiation safety.
Examples of Group IV Radiopharmaceuticals 1. 131 I NaI for treatment of hyperthyroidism 2. 32 P as soluble sodium phosphate for treatment of polycythemia vera 3. 32 P as insoluble chromic phosphate colloid for intracavitary treatment of malignant effusions.
4. 89 Sr as soluble SrCl 2 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.
Group V Radiopharmaceuticals
Includes all therapeutic radiopharmaceuticals that require hospitalization for purposes of radiation safety.
Examples of Group V Radiopharmaceuticals 1. 131 I NaI for treatment of thyroid Ca 2. 198 Au for intracavitary treatment of malignant effusions 3. Any investigational therapeutic radiopharmaceutical requiring hospitalization for purposes of radiation safety.
Group VI Radiopharmaceuticals Includes sources and devices containing byproduct material that are used for therapeutic applications.
Examples of Group VI Radiopharmaceuticals 1. 241 Am as a sealed source in a bone mineral analyzer 2. 137 Cs encased in needles and applicator cells for topical, interstitial, and intracavitary treatment of cancer 3. 60 Co encased in needles and applicator cells for topical, interstitial, and intracavitary treatment of cancer 4. 198 Au seeds for interstitial treatment of Ca
Group VI Radiopharmaceuticals 5. 125 I as a sealed source in a bone mineral analyzer 6. 128 Ir as seeds encased in nylon ribbon for interstitial treatment of cancer 7. 90 Sr sealed in an applicator for treatment of superficial eye conditions 8. 125 I as seeds for interstitial treatment of cancer
Thyroid Diseases Treatable with 131 I-NaI - hyperthyroidism (Graves disease) toxic nodular goiter (Plummer’s disease) - thyroid carcinoma (ranked in order of likelihood of 131 I uptake) 1. Follicular 2. Papillary the other two types of thyroid cancer, medullary and anaplastic, are not treatable with I-131
Decay Scheme of I-131 131 I 53
b
1
b
2
b
3
b
4
b
5
b
6 0.7229
0.6670
0.6370
14
13
12
11
8
7
5
3
10
9
6
4
2
1 0.4048
0.3644
0.3412
0.1539
0.0801
0.00
131 Stable Xe 54
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.
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.
Typical Doses of 131 I Compounds procedure route of dose (mCi) administration raiu, normal 0.005
raiu & scan, substernal 0.100
total body mets survey 5-10 hyperthyroidism 5-15 toxic nodular goiter 25 thyroid Ca therapy 75-225 oral oral oral oral oral oral
Radiation Dosimetry of 131 I- NaI following oral administration of 10 mCi dose of 131 I-NaI for treatment of hyperthyroidism, 90% of dose to tissue is achieved by
b
- emissions. For a hyperthyroid patient treated with I-131: Tissue Thyroid Testes Ovaries Whole body absorbed radiation dose (rads/10 mCi of I-131) 11,000.
9.2
9.3
16.0
Dose Determination for Therapy in Graves Disease Method 1 Measure % uptake; estimate mass of thyroid (g) Dose = 60-100
m
Ci/g x mass (g) x 100% % uptake disadvantage: since 60-100
m
Ci /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.
Dose Determination for Therapy in Graves Disease Method 2 A standard dose of 131 I 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 131 I; the other 5% require a third dose of 131 I.
Response of hyperthyroid patients to treatment with 131 I sodium iodide day of administration no immediate effect 4-6 weeks patient begins to notice beneficial effects 12 weeks 6 months maximum beneficial effects observed few observable changes after this interval
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 131 I sodium iodide for Graves disease. They are treated with synthroid daily for the rest of their lives.
Rate of Induction of Hypothyroidism Following Therapy with 131 I-NaI 35 30 25 20 15 10 5 0 1 2 3 4 5 6 7 8 9 10 years post therapy with 131 I-NaI
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
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
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
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
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.
89
Sr strontium chloride Therapy for Palliation of Bony Metastases
Physical Characteristics of 89 Sr prepared by 88 Sr(n,
) 89 Sr t 1/2 = 50.5 days type of decay:
b
maximum energy: 1.463 MeV, 100% range of
b
- in tissue: 8 mm
Advances in Cancer Therapy Longer survival in many cancers Better pain control medication More aggressive radiotherapy
End result: More people living with bone pain.
Bony Metastases in Breast 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
Therapeutic Approaches to Bone Pain NSAIDs Chemotherapy Hormonal Therapy External Beam Radiation Narcotic Therapy
Radiopharmaceutical Therapy
Historical Approach to Radionuclide Therapy Na 3 32 PO 4 in 1940’s 89 SrCl 2 in late 1980’s 153 Sm EDTMP in late 1990’s
32
P-Na
3
PO
4 1. long history 2. 60-75% response rate in literature 3. significant marrow depression end point is toxicity 4. infrequently used
89 Sr strontium chloride therapy for palliation of bony metastases 1. Indications: bone pain caused by any 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 99m Tc-MDP
89 Sr 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 89 Sr in metastases longer than in bone
89 Sr 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
Typical Dose:
89
Sr chloride 4 mCi given by IV Injection for intractable bone pain from prostate, breast cancer or other primary malignancy
Radiation dosimetry of 89 Sr chloride organ red marrow bladder wall whole body rad/mCi 80.0
0.5
6.0
89 SrCl 2 Therapy: Clinical Outcomes 80% response divided into 3 groups: moderate response morphine codeine marked response morphine advil dramatic response morphine no meds
Typical Administered Doses for
32
P Compounds
polycythemia vera soluble 32 P Na 3 PO 4 3-5 mCi IV injection malignant effusions colloidal 32 P CrPO 4 8-12 mCi intracavitary injection
32 P 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 32 P Na phosphate, interval is increased to 12 yr.
4. 11% incidence of leukemia in successfully treated patients.
32 P Na phosphate for treatment of polycythemia vera Controversy Is 11% incidence of leukemia a result of injection of 32 P 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.
Radiation dosimetry following IV injection of 4 mCi of 32 P Na phosphate.
organ absorbed dose (rads) skeleton liver spleen gonads whole body 240 24 29 4 40
32 P 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