Radionuclide Therapy

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 (gt1 MeV)
• 4. Must have high targetnon-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

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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.

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Group VI Radiopharmaceuticals

• Includes sources and devices containing
  byproduct material that are used for therapeutic
  applications.

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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
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Thyroid Diseases Treatable with 131I-NaI

• - hyperthyroidism (Graves disease)
• - toxic nodular goiter (Plummers 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

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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 0.153
9 0.0801 0.00
??14 ?13 ?12 ?11
?8 ?7 ?5 ?3
??10 ?9 ?6 ?4
?2
?1
131 Stable Xe 54
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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.

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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.

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Typical Doses of 131I Compounds

• route of procedure dose (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

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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

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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.

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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

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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.

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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
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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

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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

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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

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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

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Patient Release Criteria

• Reading lt5 mR/hr at 1 meter from patients chest,
  which is equivalent to a body burden lt30 mCi of
  I-131.

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89Sr strontium chloride

• Therapy for Palliation of Bony Metastases

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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

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Advances in Cancer Therapy

• Longer survival in many cancers
• Better pain control medication
• More aggressive radiotherapy
• End result More people living with bone pain.

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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

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Therapeutic Approaches to Bone Pain

• NSAIDs
• Chemotherapy
• Hormonal Therapy
• External Beam Radiation
• Narcotic Therapy
• Radiopharmaceutical Therapy

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Historical Approach to Radionuclide Therapy

• Na332PO4 in 1940s
• 89SrCl2 in late 1980s
• 153Sm EDTMP in late 1990s

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32P-Na3PO4

• 1. long history
• 2. 60-75 response rate in literature
• 3. significant marrow depression- end point is
  toxicity
• 4. infrequently used

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89Sr 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 99mTc-MDP

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89Sr Strontium Chloride Therapy for Palliation of
Bony Metastases

• 4. 80 Response rate overall
• 5. Ratio of metastatic lesions to normal bone
  51
• 6. Ratio of metastatic lesions to marrow
  101
• 7. Retention of 89Sr in metastases longer than
  in bone

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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

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Typical Dose 89Sr chloride

• 4 mCi given by IV Injection for intractable bone
  pain from prostate, breast cancer or other
  primary malignancy

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Radiation dosimetry of 89Sr chloride

• organ rad/mCi
• red marrow 80.0
• bladder wall 0.5
• whole body 6.0

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89SrCl2 Therapy Clinical Outcomes

• 80 response divided into 3 groups
• moderate response morphine codeine
• marked response morphine advil
• dramatic response morphine no meds

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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

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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 32P Na phosphate, interval is
  increased to 12 yr.
• 4. 11 incidence of leukemia in successfully
  treated patients.

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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.

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Radiation dosimetry following IV injection of 4
mCi of 32P Na phosphate.

• organ absorbed dose (rads)
• skeleton 240
• liver 24
• spleen 29
• gonads 4
• whole body 40

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32P chromic phosphate colloid for palliation of
malignant effusions

• 1. Intracavitary injection 10 mCi in 250 ml
  saline
• 2. gt90 of patients respond gt significantly
  decreased frequency of "tapping" required to
  remove fluid.
• 3. Rarely need to retreat patient.
• 4. Palliative, not curative.
• 5. Approved drug, lt1000 per treatment