8 Radionuclide therapy

The therapeutic use of radiopharmaceuticals is based on the concept of selective localization of radiopharmaceuticals coupled with the lethality of the same because of the tissue damage resulting from highly ionizing particulate emissions such as β particles. Principles of radionuclide therapy “

Principles of radionuclide therapy “ The radionuclide has to be concentrated at the site of the abnormality (tumor) with minimal injury to the normal tissues A variety of approaches to this problem is possible 1- Element e.g. I-131, P-32, Sr-89 2-Metabolic agents, e.g. I-131 MIBG 3-Labeled antibodies 4-Labeled cell 5- Direct administration into the cavities

Tissue factors affecting rardiopharmaceutical uptake 1- blood perfusion 2-exravascular space 3-interstitial pressure Reduction in blood flow causes -Less radiopharmaceutical is supplied to the viable cell -Hypoxic state of the cells reduces the effect of the radiation (Hypoxic cells are resistant)

Principles of radionuclide therapy 1-Radiopharmaceutical uptake (%) 2-Quantity of radiopharmaceutical 3-Retention of radiopharmaceutical 4-Physical half-life - Too short will not take full advantages of the time in the tissue - Long time gives unnecessary radiation dose to normal tissues 5-Non-homogenous uptake reduces local absorbed dose 6-selectivety of radiopharmaceutical (target to non target)

Radionuclides therapy Particle Alpha emitters ( short range: 50 µm) rarely used Beta emitters (I-131, P-32,Sr-89; range few mm) most commonly used Gamma rays (I-125)

* Thyroid I-131 Radionuclide therapy Thyrotoxicosis Differentiated thyroid cancers * P-32 therapy in myeloproliferative diseases Polycycemia rubra vera * MIBG therapy neuroblastomaand phaeochromocytomaand * Therapeutic use of radiolabelled antibodies (Target) * Palliation of bone pain (Strontium-89 and Smarium-153) bone metastases of breast and prostate

Alternative approaches to targeting therapy Injection into serous cavities -Intra-peleural therapy -Intra-peritoneal cavity -Intra-articular therapy -Direct intra-cystic injection

The thyroid Thyrotoxicosis Differentiated thyroid cancers RAI I-131 Half life 8 Principal gamma energies 360keV Principal beta Emax 0.6 MeV In the past 60 years many patients through out the world have received treatment for both thyrotoxicosis and thyroid carcinoma and the cumulative experience with this form of radionuclide therapy has confirmed its safety and efficacy

Therapy of thyrotoxicosis 1-Medical 2-Surgery 3-RAI Causes of Thyrotoxicosis Diffuse toxic goiter (Graves´ disease) Multinodular goiter (Plummer’s disease) Toxic autonomous nodule

Practical aspects of RAI therapy in thyrotoxicosis Before RI therapy it is essential that : 1-the diagnosis of thyrotoxicosis has been confirmed both clinically and biochemically (hormonal assay T3,T4,and TSH) 2-The use of radionuclide scan in the diagnosis of patients with thyrotoxicosis is very important: a-It confirms the nature of the thyrotoxicosis b- Graves’disease versus multinodular goiter Plummer’s disease c- % thyroid uptake

RAI therapy for thyrotoxicosis General consensus * It is an appropriate treatment for men and women of the middle age upwards (not usually preferred in young age) *There is no demonstrable risk associated with RAI administration *No increased incidence of leukemia and thyroid malignancies * No increased incidence of genetic defects in children born to women and man treated with RAI

Importance of RAI therapy in thyrotoxicosis Radioiodine would appear from all available data to be safe of treatment in all patients groups including: women of child-bearing years and children but excluding women who arepregnant and breastfeeding Prior to RAI therapy in thyrotoxicosis -Generally elderly patients with thyrotoxicosis should be rendered euthyroid prior to therapy to avoid unpleasant exacerbation of thyrotoxicosis -Prior to RI therapy antithyroiddrug should be discontinued for several days to ensure adequate trapping of RAI

Treatment dose, radiation dose and outcome The usual administrated dose ranges from 10mCi-20mCi (adult dose 10 mCi) The radiation dose received by family members is low but itis proportional to the close contacttime such as meal times, car travel and sleeping in a double bed The incidence of hypothyroidism in the first year ranges between 10-25% with an annual increment, depending on the amount of the administrated dose

Side effects of RI treatment -Hypothyroidism -Exacerbation of thyrotoxicosis at 7-10 days following RAI administration -Sialitis( the symptoms are usually short lived) -Alterations in taste -Radioiodine is not contra indicated in patients with dysthyroid eye disease

Thyroid carcinoma Pathology * Well Differentiated thyroid Carcinoma (WDTC) Papillary Follicular mixed Papillary and Follicular *Anaplastic ( 5%) *Medullary (10%) - WDTC in general take up RAI -Nodal metastases are presented at diagnosis in 36% of patients with papillary ca and 13% of patients with follicular ca - Distant metastases were associated with 4% of papillary ca and 16% of follicular ca

Treatment of thyroid cancer Surgery total or near total thyroidectomy Following surgical treatment RAI is the essential treatment RI has three major roles: - Diagnosis - Ablation - Treatment

Diagnosis The initial diagnostic approach following surgery is the demonstration of residual normal thyroid tissue following the removal of thyroid tumor Thyroid whole body iodine scans is performed to localize remnant thyroid tissue Thyroid remnant ablation Subsequent administration of therapy doses will be more effective if all normal thyroid tissue is ablated The ablation doses are between mCi

- Patients should be hospitalized into a special room until the level of activity fall below that permitted for discharge - Following ablation the patient should be maintained on thyroxine replacement treatment - Six months after thyroxine should be discontinued and the patient is reevaluated with I-131 whole body scan - If recurrent is demonstrated the patient should be admitted for a therapy doseof RAI

- The therapy dose will usually vary from mCi of RAI - After treatment the patient returned back on thyroxine replacement therapy - A repeat scan will be performed following an interval of 6-12months - Further therapy is given when necessary

Side effects of radioiodinetherapy -Nausea -Radiation thyroiditis -Acute and/or chronic sialadenitis -Oligospermiaor azoospermia(70%) -There are no reports in the literature of infertility, or congenital abnormalities in children treated with RAI for thyroid carcinoma

Thank you and Good Luck Prof. Dr. Omar Shebl Zahra