Radionuclide Therapy. Prof. Dr. Çetin Önsel. Cerrahpaşa Medical School Department of Nuclear Medicine. Radionuclide Therapy

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1 Prof. Dr. Çetin Önsel Cerrahpaşa Medical School Department of Nuclear Medicine

2 Principles of radionuclide therapy (1) 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 Element e.g. I-131, P-32, Sr-89 Metabolic agents, e.g. I-131 MIBG Labeled antibodies Labeled cell Liposomas Direct administration into the cavities Vascular blockade, e.g. labeled lipiodol or microsphere

3 Principles of radionuclide therapy (2) Tissue factors affecting rardiopharmaceutical uptake Changes in blood perfusion Increases in exravascular space Changes in interstitial pressure Reduction in blood flow causes Less radiopharmaceutical is supplied to the viable cell Demand for metabolic substrates is less Hypoxic state of the cells reduces the effect of the radiation

4 Principles of radionuclide therapy (3) Radiopharmaceutical uptake and retention Quantity of radiopharmaceutical Retention of radiopharmaceutical Physical half-life Too short will not take full advantages of the residence time in the tissue Long time gives unnecessary radiation dose to normal tissues Non- homogenous uptake reduces local absorbed dose No radiopharmaceutical is entirely selective (normal thyroid tissue and thyroid cancer) Pharmaceutical intervention may enhance uptake

5 Principles of radionuclide therapy (3) Radionuclides for therapy Alpha emitters (Bi-212, short range: 50-90µm) Beta emitters (I-131, P-32, Sr-89; range >1mm) Auger and Coster-Kronign (I-125; <10A)

6 (1) The thyroid Thyrotoxicosis Differentiated thyroid cancers P-32 therapy in myeloproliferative diseases Polycytemia vera Essential thrombocythaemia MIBG therapy in neuroblastoma and phaeochromocytoma and paraganglioma Therapeutic use of radiolabelled antibodies Palliation of bone pain (Strontium-89) Metastases of breast and prostate

7 (2) Alternative approaches to targeting therapy Injection into serous cavities Intra-peleural therapy Intra-peritoneal cavity Intra-articular therapy Direct intra-cystic injection Intra-vascular injection

8 The thyroid (1) Thyrotoxicosis Differentiated thyroid cancers I-131 (RI) Half life 8.04 Principal gamma energies 80keV-364keV Principal beta Emax 0.61 MeV In the past 60 years many patients throughout 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

9 The thyroid (2) Therapy of thyrotoxicosis Medical Surgery RI Causes of Thyrotoxicosis Graves disease (overproduction of an antibody to the TSH receptor) Toxic autonomous nodule or nodules (Plummer s disease) Subacute viral thyroiditis Iodine induced thyrotoxicosis Thyrotoxicosis factitia

10 Practical aspects of RI therapy in thyrotoxicosis Before RI therapy it is essential that the diagnosis of thyrotoxicosis has been confirmed both clinically and biochemically The use of radionuclide scan in the diagnosis of patients with thyrotoxicosis is very important: It confirms the nature of the thyrotoxicosis Thyroid scan is particularly valuable in patients who have developed Graves disease in a multinodular goiter as a mistaken diagnosis of Plummer s disease

11 RI therapy in thyrotoxicosis General consensus It is an appropriate treatment for men and women of the middle age upwards There is no demonstrable risk associated with RI administration No increased incidence of leukemia and thyroid malignancies The risk of surgery in both children and adults In children acute complications in between 16-35% treated with subtotal thyroidectomy Permanent complication occurs up to 8% of children No increased incidence of genetic defects in children born to women and man treated with RI

12 Importance of RI 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 are pregnant and breastfeeding

13 Prior to RI 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 antithyroid drug should be discontinued for several days to ensure adequate trapping of RI

14 Treatment dose, radiation dose and outcome The usual administrated dose ranges from 2mCi-15mCi The radiation dose received by family members is low but it is proportional to the close contact time such as meal times, car travel and sleeping in a double bed The incidence of hypothyroidism in the first year ranges between 7-25% with an annual increment of 2-4% depending on the size of the administrated dose

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

16 Thyroid carcinoma (1) Pathology Papillary (65%) Follicular (25%) Anaplastic ( 5%) Medullary (10%) Papillary and follicular thyroid cancers in general take up RI 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

17 Thyroid carcinoma (2) Initial treatment of thyroid cancer is total or near total thyroidectomy Following surgical treatment RI ablation or treatment is essential The role of RI RI has three major roles: Diagnosis Ablation Treatment

18 Thyroid carcinoma (3) Diagnosis The initial diagnostic approach is the demonstration of residual normal thyroid tissue following the removal of thyroid tumor Thyroid remnant ablation Interpretation of subsequent thyroid whole body iodine scans is simplified Interpretation of thyroglobulin levels is also aided Subsequent administration of therapy doses will be more effective if all normal thyroid tissue is ablated The ablation doses are between mCi

19 Thyroid carcinoma (4) Patients should be hospitalized into a dedicated room until the level of activity fall below that permitted for discharge Following ablation the patient should be maintained on TSH suppressive dose of thyroxine 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 dose of RI

20 Thyroid carcinoma (5) The therapy dose will usually vary from mCi of RI After treatment the patient recommences thyroxine A repeat scan will be performed following an interval of 6-12months and further therapy is given when necessary When a negative tracer has been acquired follow up can continue using thyroglobilin measurement An elevated value will indicate the need for the patient to be rescanned to assess the possible metastatic site

21 Side effects of radioiodine therapy Nausea Radiation thyroiditis Acute and/or chronic sialadenitis Oligospermia or azoospermia (70%) There are no reports in the literature of infertility, miscarriage prematurity or congenital abnormalities in children treated with RI for thyroid carcinoma

22 P-32 therapy in myeloproliferative diseases

23 P-32 therapy in myeloproliferative diseases Myeloproliferative diseases Polysytemia vera Essential thrombocythaemia

24 P-32 therapy in Polycytehameia vera (PV) PV is characterized by an increased production of red blood cell but not an increased blood cell survival The production of red blood cells can be as high as 2-3 times the normal production rate Transitions from PV to myeloid metaplasia and acute leukemia are common Between 25-50% of patients with myeloid metaplasia phase will eventually undergo leukaemic transformation The median age at diagnosis is 60 years

25 P-32 therapy in Polycytehameia vera (PV) The median survival of patients with an untreated PV is approximately 1.5 years The optimal treatment is not available Treatment modalities Chemotherapy with chlorambucil, busulfan or hydrxyurea Phlebotomy Radiophosphorus

26 P-32 Pure beta emitter Mean range in tissue is about 3mm Suppress hyperproliferative cell lines rather than to eradicate them It is taken up primarily in the bone, spleen and liver The high radiation dose delivered to the bone marrow account for the treatment effect in PV

27 P-32 therapy in Polycytehameia vera (PV) P-32 was compared with phlebotomy alone and chlorambucil Chlorambucil leads to a reduction in survival in comparison with the other two treatment modalities The phlebotomy-treated patients developed a higher percentage of fatal thromboembolic complication P-32 was compared with busulphan Busulphan produced a survival advantage The prevalence of acute myeloic leukemia was less than 2% in both the treatment

28 P-32 therapy :Treatment recommendation The treatment should be preceded by repeated phlebotomies to reduce the haematocrit to 42-47% Then a standard dose of 3-5 mci P-32 is administered iv In the absence of response a second treatment is given after 3 month, this time with a 25% increase in dose This procedure, with dose augmentation, should be repeated every 3 months until an adequate response is obtained Especially in elderly patients who have more limited survival because of their age P-32 is an effective agent in the management of PV

29 P-32 therapy in essential thrombocythaemia P-32 therapy can also be used an alternative treatment in patient with essential thrombocythaemia It has resulted in a 63% complete remission rate and 37% partial remission rate