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 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
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. 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.
Group V Radiopharmaceuticals
Includes all therapeutic
radiopharmaceuticals that
require hospitalization for
purposes of radiation safety.
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.
Group VI Radiopharmaceuticals
Includes sources and devices
containing byproduct material
that are used for therapeutic
applications.
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
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
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
Decay Scheme of I-131
131
I
53
b1
b2
b3
b4
0.7229
0.6670
0.6370
14
13
12 11
8 7
5
3
0.4048
0.3644
0.3412
b5
b6
10 9
6
4
2
1
131
Stable
Xe
54
0.1539
0.0801
0.00
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
procedure
131I
Compounds
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
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:
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 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.
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.
Response of hyperthyroid patients to
treatment with 131I sodium iodide
day of administration
4-6 weeks
no immediate effect
patient begins to
notice beneficial effects
12 weeks
maximum beneficial
effects observed
6 months
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 131I 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 131I-NaI
% hypothyroid
35
30
25
20
15
10
5
0
1
2
3
4
5
6
7
8
years post therapy with 131I-NaI
9
10
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.
89Sr
strontium chloride
Therapy for Palliation
of Bony Metastases
Physical Characteristics of 89Sr
prepared by 88Sr(n,)89Sr
t1/2 = 50.5 days
type of decay: bmaximum 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
Na332PO4 in 1940’s
in late 1980’s
89SrCl
2
153Sm
EDTMP in late 1990’s
32P-Na PO
3
4
1. long history
2. 60-75% response rate in literature
3. significant marrow depressionend point is toxicity
4. infrequently used
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
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
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
Typical Dose:
89Sr
chloride
4 mCi given by IV Injection
for intractable bone pain
from prostate, breast cancer
or other primary malignancy
Radiation dosimetry of 89Sr chloride
organ
red marrow
bladder wall
whole body
rad/mCi
80.0
0.5
6.0
89SrCl
2
Therapy: Clinical Outcomes
80% response divided into 3 groups:
moderate response morphine
marked response morphine
dramatic response morphine
codeine
advil
no meds
Typical Administered Doses
32
for P Compounds
polycythemia vera
soluble 32P Na3PO4
3-5 mCi
IV injection
malignant effusions
colloidal 32P CrPO4
8-12 mCi
intracavitary
injection
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.
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.
Radiation dosimetry following IV
injection of 4 mCi of 32P Na phosphate.
organ
absorbed dose (rads)
skeleton
liver
spleen
gonads
whole body
240
24
29
4
40
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