Case Study TH
Radionuclide Therapies
NMED 462
Purpose of Course
Define Types of Radiation-based Therapies
Define Purpose of RN Therapy in NM
Review Bone Met and Thyroid Therapy Options
Introduction
Ionizing radiation affects cells
Sufficient quantities may kill cells or alter cells
May be used for therapeutic purposes such as cancer treatment
WHY??
Introduction
Law of Bergonié and Tribondeau
Immature (primitive) cells are more sensitive than mature cells
Younger tissues and organs are more sensitive than older tissues and organs
Higher metabolic activity (highly active) = higher sensitivity
Greater growth rate (multiplication rate) = higher sensitivity
Rad Bio - p. 8
Introduction
More radiosensitive cells are:
Cells that have a high division rate
Cells that have a high metabolic rate
Cells that are of a non-specialized type (primitive)
Radiosensitive Cells
Germinal cells
Lymphoid cells
Basal cells
Hematopoietic cells
Epithelium of GI tract
Germ cells
Lymphoid Cells
Basal cells
GI Epithelium
Radiosensitive Cells
Gonads are very radiosensitive
Females
Temporary sterility 1.5 Gy (150 rad)
Permanent sterility 5 Gy (500 rad)
Males
Temporary sterility 2.5 Gy (250 rad)
Permanent sterility 6 Gy (600 rad)
Pregnancy and Minors
Children should be expected to be more radiosensitive than adults
Fetuses more radiosensitive than children
Embryos even more radiosensitive, especially in the first weeks of pregnancy when organs are forming
Remember: High division, High metabolic, Non-specialized!!
Radio-resistant Cells
Bone
Liver
Kidney
Cartilage
Muscle
Nerve
Radio-sensitivity of Various Cell Types
| Radiosensitivity | Cell Type |
| Low | Muscle |
| Nerve | |
| Intermediate | Osteoblast, Endothelial |
| Fibroblast, Spermatids | |
| High | Spermatogonia, Lymphocytes |
| Stem cells, Intestinal Mucosa cells, Erythroblasts |
Therapy for Cancer
CA cells are usually more radiosensitive than normal tissue
Primitive, rapid growth over a long period of time
Not all malignant tumors are radiosensitive to the amount of radiation administered
Patient’s complete therapy program may include:
Surgery
Chemotherapy
Radiation
Teletherapy
Most common form of therapy used in medical field
Treatment using external beam of radiation from a distance
Radiation beam is produced from an outside source and directed towards the target area
Effective for deep lesions where surgery would not be an option
Teletherapy
“Fractionate” dose
Total dose in Rads is given in multiple smaller increments over time
Minimizes side effects
Allows for better recovery time for affected healthy cells
Teletherapy
Linacs
Linear accelerators are used in a therapy department
Generate high energy photons (up to 200 MeV) which are carefully aimed at the area and may be used from head to toe
More advanced Linacs have capability to deliver another type of treatment, electrons instead of photons, to treat areas that are on or close to the skin's surface
Teletherapy
Intensity Modulated Radiation Therapy (IMRT)
Type of stereotactic radiotherapy that allows the clinical oncologist to treat CA with less exposure to healthy tissue
The linear accelerator moves the Multi-Leaf Collimators (MLC’s) while the radiotherapy treatment is taking place
Allows the radiation dose to be modulated (shapes the beam) very accurately around the tumor
IMRT also allows higher radiation doses to be given to the patient with fewer side effects
Teletherapy
IMRT is not suitable for all treatment areas
IMRT technique benefits patients being treated for:
pelvis (prostate or gynecological CA)
head and neck CA
The image above shows a cross-section of a patient's head. The colored lines show physicians where the radiation dose is targeted.
Teletherapy
A very popular linacs system today is the CyberKnife system
Utilizes a robotic arm linacs for treatment
Continuously monitors movement, not requiring the patient to be immobilized
Brachytherapy
“Short-distance” radionuclide implant therapy
Used for long or short-term treatment
Sealed sources (catheter or seeds) surgically placed inside patient
May use removable or permanent implants
Radiation focused on area of implantation
Brachytherapy
Commonly used for cancers in these areas:
Breast
Cervical
Coronary/Vascular
Skin
Usually permanent
Brachytherapy for Liver
Brachytherapy for Liver CA
Liver CA can be primary or metastatic origin
Other treatment options include:
Surgical resection
Chemotherapy
Hepatic artery embolization
Cryotherapy
Radiofrequency ablation
Radiation therapy
Brachytherapy for Liver
Selective Internal Radiation Therapy (SIRT)
Treatment of primary and metastatic liver CA using Y-90 microspheres
Treatment of Hepatocellular Carcinoma (HCC)
A primary liver tumor
Treating liver metastasis from primary colorectal CA
Y-90 Microspheres
Pure Beta emitter
0.94 MeV, 2.67 day T½
Mean range in tissue is 2.5 mm, max 10 mm
Y-90 TheraSpheres
Glass microspheres
Resin microspheres
“Selective Internal Radiation” Spheres
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Y-90 Microspheres
Advantages include:
localizing radiation dose to tumor while sparing healthy tissue
Reducing chemotherapy-associated morbidity
Increased survival rate
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Y-90 Microspheres
Particle size = 20-60 µm
Prevents spheres from leaving tumor
Administered via catheter into hepatic artery
Lodges in small vessels of tumor
Hypervascular
Tumor : Normal Tissue uptake = 200:1
Dose range = 81-540 mCi (varies due to desired rad dose to tumor)
Y-90 Microspheres
Extrahepatic arterial shunting of microspheres to lungs and GI may occur, causing adverse effects to these organs
Prior to administration of Y-90, 2-4 mCi of Tc-99m MAA may be administered via hepatic arterial catheter
Imaging determines extent of shunting to lung and absence of gastric and duodenal flow
Y-90 Microspheres
Contraindications
AV shunting > 20%
Portal vein thrombosis
2% lung uptake
30% lung uptake
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Y-90 Microspheres
SPECT imaging from Brems may be used to confirm localization
Performed as outpatient therapy
No special restrictions or precautions
Small amount of activity is excreted in urine
Brems Imaging
Bone Mets Therapy
P-32 Sodium Phosphate
Metastron®
Quadramet®
Bone Mets Therapy
~ 50% of breast/prostate cancer patients develop bone mets
Lungs, thyroid, and kidney CA commonly metastasize to bone
Causes severe pain
Therapy decreases pain in 40-80% of patients
Therapy effects last several weeks; up to six months
Used for palliative treatment only, not cure
Bone Mets Therapy
Therapy Goals
Preserve function
Increase mobility
Relieve pain
Decrease need for narcotics
Increase quality of life
Bone Mets Therapy
Patient’s expected life span should be > 3 months
Contraindications
No bone pain
Solitary Mets site
Compromised bone marrow
Bone Mets Therapy
Therapy suppresses bone marrow
Platelets must be > 60,000
WBC must be > 2400
Monitor blood every 2 weeks, until platelets recover
Platelets take about 12 weeks to recover
WBC’s require about 6 months to recover
Bone Mets Therapy
Three RP’s approved by FDA
P-32 Sodium Phosphate
Sr-89 Strontium Chloride (Metastron®)
Sm-153 Lexidronam (Quadramet®)
P-32 Bone Mets Therapy
P-32 Sodium Phosphate
HL = 14.3 days, 1.71 MeV beta, no gamma
Dosage = 5 mCi
IV or oral
60-90% have decreased bone pain within 5-14 days
Equally effective for treatment as Sr-89, but yields greater myelosuppression
Metastron®
Sr-89 Strontium Chloride
HL = 50.5 days, 910 keV beta, no gamma
Expires 28 days after calibration
Dose = 40-60 µCi/kg (average of 4 mCi)
Inject IV over 1-2 min
Flush with 10 ml normal saline
Metastron®
Calcium analog – targets areas of active osteogenesis
Relief in 1-3 weeks
Treatment lasts 4-6 months
20% become pain free
65-80% decreased pain
Treatment may be repeated, but no sooner than 90 days
Metastron®
Flare response in 10-20% of patients
Within 2-3 days of treatment, pain may worsen before it gets better
Treat pain with non-aspirin drugs
Should be no nausea, vomiting, or hair loss
Radiation dose to healthy bone
Surface = 63 rads/mCi
Bone Marrow = 41 rads/mCi
Quadramet®
Sm-153 Lexidronam
Sm-153 EDTMP = ethylene diamine tetramethylene phosphate
810 keV beta, 103 keV gamma
HL = 46.3 hrs
Frozen solution
Expires 48 hrs post calibration
Expires 8 hrs post thaw
Quadramet®
Localization in lesions and normal bone is similar to Tc-99m Medronate
Hydroxyapatite via chemisorption
Ratio of tumor : normal bone
5:1
Bone surface ~ 25 rads/mCi
Bone marrow suppression similar to Sr-89
Platelets suppressed 5-6 weeks, full recovery within 12 weeks
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Quadramet®
Dose = 1 mCi/kg IV
10 ml normal saline flush
Image WB or ROI @ 3-48 hrs
Confirms skeletal/Mets uptake
Quadramet®
35% relief in 1 week
70% relief in 4 weeks
39% still have relief at 16 weeks
Low flare response ~ 7%
Advantages
Short HL results in high dose rate over short period providing rapid onset of pain relief and limited bone marrow suppression
4-6 hrs post dose, urinary excretion is complete and uptake in bone is related to extent of Mets present, not dose administered
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Hyperthyroidism Therapy
I-131 Therapy
Hyperthyroidism
Historically effective treatment
Used since early 40’s
Simple, safe, inexpensive
Goal
Irradiate thyroid gland to the point of reducing hormone levels from overactive to normal function
Risk
May irradiate to point of inducing hypothyroidism
Treat hypothyroidism with thyroid hormone, such as Synthroid®
Hyperthyroidism
Normal Thyroid Uptake Levels
Four-hour uptake = 5-15%
24-hour uptake = 10-35%
Iodine therapy may be required depending on how high uptake results or lab (T3, T4) results are
Hyperthyroidism
Effects
Gland increases 2-3 times normal size
Secretes excessive amounts of thyroid hormone (5-15 times more)
Thyroid Stimulating Hormone (TSH) are very low or essentially zero
Hyperthyroidism
Types
Graves’ Disease
Gland is a diffusely enlarged goiter
Autoimmune disorder – thyroid stimulating immunoglobulins stimulate the TSH receptors
Toxic nodular goiter
Gland that contains autonomously functioning thyroid nodules
Plummer’s Disease
Form of Toxic Nodular Goiter, where gland may contain solitary or multiple autonomous nodules, elevated T3 and T4, low TSH
Hyperthyroidism
Radiopharmaceutical
I-131
HL = 8 days
Energy = 364 keV gamma, 606 keV beta
Thyroid gland metabolizes Iodine at extremely high levels
Localizes via active transport
Hyperthyroidism
Dosage Determination
I-131 Dose (mCi) = Gland Wt. (g) x # uCi desired per g % 24 hr. uptake x 10
Hyperthyroidism
Wide variation in recommended activity dose
Generally between 55-200 µCi per gram
Higher doses used for patients with severe hyperthyroid symptoms or underlying cardiac problems, in which induced hypothyroidism would be advantageous
Hyperthyroidism
Typical Dose
Graves’ Disease
10-15 mCi
Toxic Nodule Goiter / Plummer’s
15-29 mCi
Dose may be in liquid or capsule form
Capsule is the most common
90% of patients acquire normal thyroid function (euthyroid) or may become hypothyroid with 10 mCi
Relapse rate of approximately 10-25%
Hyperthyroidism
Patient Prep
Low Iodine diet 1 week prior to therapy
No Iodine contrast 3 weeks prior to therapy
Patient discontinue thyroid meds 2-4 weeks prior to therapy
Nursing females must discontinue nursing until therapy and follow-up studies are completed
Hyperthyroidism
Contraindications
Pregnancy
Nursing
Iodine allergy
Recent MI
Recent thyroid meds or iodine-based diet
Patients who regurgitate easily
Administer Reglan® if necessary (antivomitus)
Hyperthyroidism
Procedure
ID patient (2 forms of ID)
Verify pregnancy test results, minimum 72 hrs prior to dose administration
Obtain informed consent
Explain procedure
Discuss safety precautions
Dose
Administer potassium-iodide post 131I therapy to inhibit hormone release from gland post dose
Hyperthyroidism
Safety Precautions
Associated restrictions to be followed post dose (generally 48 hrs but follow departmental protocol):
No intimate contact
No holding children or pets
Flush toilet twice
Wash clothes in separate loads
Use disposable plates, utensils
Minimize public contact to less than 1 hr
Double up on fluids
Hyperthyroidism
Results
Thyroid storm (<0.1 %)
Gland size decreases before hyperthyroidism is under control
Lab work is best indicator of results
T3, T4
Evaluate patients in 2-3 months
Re-dose if necessary in 3-4 months
I-131 Ablation Therapy Treatment of Thyroid Cancer
CA metastasizes to regional lymph nodes or bone
CA limited to neck
Ablation of residual functioning thyroid carcinoma following surgery
Ablation of residual functioning normal thyroid tissue after total or partial thyroidectomy (preventative)
Ablation
Patient Prep
ID patient – verify doctor’s order
Low Iodine diet 1 week prior
Discontinue thyroid meds 2-4 weeks prior
No Iodine contrast 3 weeks prior
No pregnancy/nursing
Ablation
Contraindications
Allergy to Iodine
Did not follow the low Iodine diet, thyroid meds, and contrast precautions
Patient likely to regurgitate dose
Administer Reglan® if necessary (antivomitus)
Ablation
Dose
Oral administration
Capsule vs. liquid
30-300 mCi I-131
I-131 Beta = 1 rad/uCi administered
Most destruction is caused by 606 KeV beta particles causing ionization and chromosomal damage
Ablation
In Patient Protocol
Out-Patient Protocol
Old Regulations
Hospitalize
Force fluids
Collect/monitor urine
Survey patient
See Shackett p. 319-322
May still be on hospital license
New Regulations
Dose & Release
Dose specific calculations determine restrictions
Sleep alone
Flush toilet twice
No holding children/pets
Avoid public locations
Wash clothes separately
Disposable dishes, etc.
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Ablation
Patient dosed in room
Private room with bath
Corner room
Patient restricted to room
Post radiation signs
Cover phone, TV remote, call button, and other small items commonly handled by patient with plastic
Ablation
CHUX over floor near bed, bathroom floor, back of toilet, table tops, chair
Mattress, pillow covered with plastic
Mark floor with tape-line where visitors must remain behind
Approximately 1 meter from the patient
Visitors only stay about 20 min per day
No pregnant visitors allowed
Ablation
Items in room must be surveyed prior to removal
All “hot” items must be stored for decay
Survey room post discharge, decontaminate as necessary
Ablation
Typical dose rates to others @ 1 meter
0.185 mrem/mCi immediately post dose
0.11 mrem/mCi @ 2-4 days
0.07 mrem/mCi @ 5-7 days
NRC Regs – records for release kept for 3 years
Ablation
Exit Instructions
Similar to Hyperthyroid restrictions
Avoid children & pregnant women
Stress time and distance
Saliva contamination
Ablation
Scan patient following TP
Follow-up @ 6-12 months (WB scan)
Can re-dose 6-12 months as needed
May follow-up with PET scan following ablation to check for METS
Half way there!
Don’t give up!