Transcript Radionuclide Therapy

Radionuclide Therapy
Department of Nuclear Medicine
Renji Hospital
School of Medicine
Shanghai Jiaotong University
Yan Wei-Li M.D.
Irradiation
External Irradiation
Internal Irradiation
Radionuclide therapeutics has a
long history. It can provide
relatively effective treatments for
various diseases that are difficult
to cure or hard to get satisfactory
results in clinical practice
The fundamental theory for radionuclide
therapy is to achieve appropriate
treatment for the disease through delivery
of radiation dose at the desired cytotoxic
level with the defined endpoints being cure,
disease control or palliation, and at the
same time avoid or minimize toxic effects,
both in acute frame and as long term
complications
Internal irradiation
Selective internal irradiation therapy
(Interstitial irradiation)
Intracavitary irradiation /
intraluminal interventional therapy
Contact therapy
radionuclide seed implanting
therapy
brachy radiotherapy
Interstitial irradiation
Interstitial Irradiation is a
technique where the radioactive
source is placed in the Interstitial
of the organ/tumor mass thereby
delivering a high local radiation
dose to the tumor
Intracavitary irradiation (ICI)
ICI is a technique where the
radioactive source is placed in the
lumen of the body thereby delivering
a high local radiation dose to the
tumor
Contact therapy
Contact Therapy is a technique
where the radioactive source is
placed in the surface of the
cutaneous thereby delivering a high
local radiation dose to the foci
Principal of radionuclide therapy
Ionization and energy transfer
Direct interaction
biological molecules: DNA etc.
Indirect interaction
free radical: H+、OH-、H2O2 etc.
maladjusted inner entironment
Radiopharmaceutical
Pharmaceutical
Radionuclide
32P、131I、125I 、103Pd 、89Sr、
153mSm、90Y、186Re、188Re、192Ir
Index of radionuclide
LET (linear energy transfer)
RBE (Relative biological effectiveness)
T1/2 (half-life)
Volume of interaction
Scale of tumor
Nuclides for radionuclide therapy
I : -particle emitter:
50~90μm = diameter of ten cells
211At
、223Ra、225Ac etc.
II: -particle emitter
<2OOum、20Oum~lmm、 >lmm
131I、32P、89Sr、90Y
etc .
II: Auger electron and internal conversion
electron emitter
10mm
125I etc.
Radioiodine therapy of
hyperthyroidism
Hyperthyroidism can be simply
defined as a hypermetabolic state
induced by excess thyroid
hormone
Treatment of hyperthyroidism
Drug
Surgery
Radioiodine
Principle of radioiodine therapy
Selective uptake by hyperfuctioning
thyroid cell
Emission range of beta ray have only 12mm in tissue and deliver greater
ionization effect,cause focal fibrosis
A prolonged time of stay of radioiodine
in thyroid,average effective T1/2=3-5
days
Indication of radioiodine therapy
Patients who are Grave’s disease with
moderate symptom and signs, age above 25
years
Patients who are poor surgical risks or
refuse to operation
Patients who have recurrence following
surgical or medical therapy
Patients who are not effect or allergic to
antithyroid drugs
Patients whose effective half time of 131I in
thyroid is over 3 days
Relative contraindication
Patients who have severe
hyperthyroidism
Patients whose leucocyte count is
below 3.0×109/L, or PLT count
80×109/L
Patients whose effective half time
of 131I in thyroid is less than 3 days
Absolute contraindication
Patients who are in pregnancy and
lactation
Patients who have large goiter with
press syndrome and sign
Patients who have severe hepatic and
renal insufficiency
Patients who have hyperthyroidism
complicated with recent myocardial
infarction
Patient preparation
Patients should discontinue iodine
containing drug and food affecting the
thyroid uptake before treatment, same
as the RAIU
Patients should undergo RAIU test and
determine the effective T1/2 of 131I
Estimate the weight of the thyroid
gland usually by palpation
Patients can be treated with beta
receptor blockers if necessary
Dose calculation
Often use one dose method
131 I dose uptake measurement
thyroid weight (g)×100μci/g
131
I (μCi)=
131
I Max%uptake
Side effect
Mild gastrointestial reaction but rarely
occurred
Thyroid crises in sever cases or not
well controlled patients
Hypothyroidism
Temporary occurrence:within 3-6 months.
Permanent occurence:after 6 months
Evaluation of therapeutic effect
Symptom and sign improved after 3-6
months
Completely alleviated 6 -24 months
One dose cure rate reach 55-77%
Total cure rate
80-90%
Failure rate
2-4%
Recurrence rate 1-4%
Radioiodine therapy of
thyroid cancer
Thyroid carcinomas are classified as
papillary
70~80%
follicular
15%
medullary
5~10%
undifferentiated or anaplastic 5%
Pathology
Well-differentiated papillary and
follicular carcinomas are slow-growing
and carry a relatively good prognosis
poorly differentiated follicular and
anaplastic carcinomas are aggressive
tumors with a poor prognosis
Pathology
Papillary carcinomas are more likely to
be found in regional nodes(36%) than
follicular carcinoma(13%),but follicular
tumors are more often distantly
metastasis than papillary carcinoma
Eighty-five percent of thyroid cancers
will be functional papillary or follicular
carcinomas, capable of concentrating
iodine
Clinical patterns
These tumors usually present as a firm
neck mass, or accompanying palpable
lymphadenopathy
Scans of thyroid nodules showed that
the nodule was cold 84%of the time
airway obstruction , dysphagia, and
hoarseness indicate invasive disease
Ablation of normal thyroid
gland remnant
Implication of ablation of
residual tissue
Thyroid cancer tends to be multifocal, and
any remnants of thyroid gland could
contain malignancy
Occult tumor may be found and killed with
an ablation dose
If one removes all function tissue, one can
use the serum thyroglobulin level later as
a diagnostic test to monitor recurrence
Implication of ablation of
residual tissue
Normal thyroid tissue has a significantly
greater affinity for iodine than functioning
thyroid canrcinoma, and so detection and
treatment of carcinoma are difficult as long
as normal tissue is allowed to persist
Hormone secretion by normal tissue
inhibits endogenous pituitary TSH
stimulation of 131I uptake by tumor
Indication
Include all patients with well-differentiated
thyroid carcinoma and residual
postsurgical thyroid tissue or tumor with
affinity for iodine
Contraindication
Patient who are in pregnancy and lactation
Patients who are below 3.0×109/L of
leucocyte count or with severe hepatic and
renal insufficiency
Patients who are poorly differentiated
thyroid carcinoma or with no affinity for
iodine in focus
Treatment of metastatic
thyroid carcinoma
Indication
Patients with well-differentiated thyroid
carcinoma who have recurrence and residual
postsurgical tumor, with affinity for iodine
Patients with well-differentiated thyroid
carcinoma who have function metastatic foci,
with affinity for iodine
Patients with well-differentiated thyroid
carcinoma who have function metastatic foci,
and cannot be operated
Contraindication
patients who are pregnancy and
lactation
Patients who are below 3.0109 /L of
leucocyte count or with severe hepatic
and renal insufficiency
Patients who are poorly differentiated
thyroid carcinoma or with no affinity for
iodine in focus
Selection of therapeutic dose
When the radiation dose to metastatic
lesions exceeded 8,000 rads, 98% of
lesions responded to treatment while none
responded to doses less than 3,500 rads.
It has excellent results using an empirically
administered activity of 150 to 175 mCi for
cervical node metastases, 175 to 200 mCi
for pulmonary metastases, and 200 mCi
for skeletal metastatic disease
Side effect
Cytopenia
Radiation pneumonitis
Gastrointestinal radiation
Acute and/or chronic sialadenitis
Radionuclide therapy of
bone metastasis and
bony pain
Introduction
Bone metastasis is a common sequela
of solid malignant tumors such as
prostate, breast, lung, and renal
cancers, which can lead to various
complications, including fractures,
hypercalcemia, and bone pain, as well
as reduced performance status and
quality of life
Introduction
Use of conventional radiography and
bone scanning helps confirm the
presence of bone metastasis but can
also assess the extent; classify the
lesions into predominantly osteoblastic,
osteolytic, or mixed type; and, finally,
stratify those lesions that are at risk for
fracture or cord compression
Treatment of bone pain
Analgesic Therapy
External Beam Radiation Therapy
Hormonal Therapy and Chemotherapy
Surgical Intervention
Radioisotope therapy
Analgesic therapy
Analgesic medications are the first line
of treatment for bone pain in cancer
Step1: aspirin, ibuprofen, and
naproxen
Step2: codeine
Step3: morphine
External Beam Radiation
Therapy
Conventional palliative external beam
radiation therapy (EBRT) for painful
metastases includes several different
local and wide-field methods. It has
been shown to be effective in relieving
pain 60%–90%
Hormonal therapy and
chemotherapy
Hormonal therapy appears to be
effective only in patients with breast or
prostate cancer
breast cancer:
Tamoxifen and aminoglutethimide
prostate cancer:
antiandrogens, estrogens
Surgical intervention
In some cancers, patients may
require various types of surgical
intervention
Cord compression
Fractures
Radioisotope therapy
Most of these agents are administered
intravenously and target the painful
bone metastases by accretion to the
reactive bone sites with a high targetto-nontarget tissue ratio and a very low
concentration in the surrounding
normal bone, underlying bone marrow,
or other structures
Radioisotope therapy
The goals of systemic radioisotope
therapy include alleviating pain;
improving the quality of life; decreasing
the amount of opioids, radiation, and
chemotherapy used; and improving
outcomes and survival. Systemic
radioisotope therapy may reduce the
overall long-term cost of pain palliation
while improving the quality of life of
cancer patients with bone pain
153Sm
153Sm
has a physical half-life of 46.3 h
and decays with emissions of both ßand γ-particles. The maximum ßparticle energies are 810 keV (20%), 710
keV (50%), and 640 keV (30%), and the
γ-photon energy is 103 keV (29%).
153Sm
Using the 103-keV photon, the
biodistribution of 153Sm-lexidronam can
be imaged with a gamma camera
Strontium-89
89Sr has
a physical half-life of 50.5 d and
decays by β-emission with an energy of 1.46
MeV; it is typically used as the chloride salt.
The maximum range of the ß-particle in
tissues is 8 mm
the concentration of 89Sr at sites of
metastasis may be as high as 5–10 times that
in normal bone, with the dose to the tumor
averaging 20–24 Gy
Indication
Patients who have bone metasteses
proved by clinical, X-rays and skeletal
imaging. It is better for multifoci bone
metastasis and bone metastasis
resulted from prostate, breast and lung
Patients who have severe bone pain
resulted from bone metastasis. Other
treatment has no effect
Patients who are above 3.5109/L of
leucocyte count，and PLT>80109/L.
Contraindication
Patients who have osteolytic
cold region in skeletal imaging
Patients who are below 3.0109
/L of leucocyte count or severe
hepatic and renal insufficiency
Dose
The dose of 153Sm-EDTMP is from
0.8 to1.2 mCi/kg.
The patients received 30 µCi/kg ~
40 µCi/kg with 89Sr
Evaluation
Positive responses occurred at all
dose levels of 153Sm-EDTMP from 7.4
to 37 MBq/kg (0.8–1.2 mCi/kg).
Between 70% and 80% of all patients
experienced partial or complete relief
of pain. 50% had responses lasting
>8 wk with the response being
independent of dose. Retreatment
with 153Sm-EDTMP has been
described as safe, feasible, and
efficacious
Evaluation
In general, pain palliation was observed
at 1 wk after administration of the agent
and was independent of dose. In all
clinical studies, approximately 10% of
patients exhibited a painful flare
response within 48 h after receiving
153Sm-EDTMP
Evaluation
There was a consistent fall in platelets
and WBCs; the magnitude of the fall
was dose dependent. A fall in
circulating platelets was observed 1–2
wk after treatment with 153Sm-EDTMP;
the nadir value was reached at 4 wk
and values began to return toward
normal after 5–8 wk
Strontium-89
The patients received 1.11 MBq/kg (30
µCi/kg)~ 1.48 MBq/kg (40 µCi/kg).
The overall response rate in terms of
decreased pain or improvement in quality of
life (or both) was about 80%.
Painful flare responses were seen in
approximately 10%–20% of patients treated
with 89Sr. These were usually transient and
generally appeared subsequent to good
responses to the administered 89Sr