RADIONUCLIDETHERAPY放射性治疗.ppt

1、,RADIONUCLIDE THERAPY,Characteristics of an ideal therapeutic radiopharmaceutical,Radiopharmaceuticals in therapy,Contents,Radioiodine therapy of hyperthyroidismRadioiodine therapy of thyroid carcinomaRadionuclide therapy of bone metastasis,Hyperthyroidism can simply be defined as a hypermetabolic s

2、tate induced by excess thyroid hormone. It can develop secondary to thyroid hormone released from over-active or inflamed thyroid gland or introduce from an extraglandular source. The common cause of hyperthyroidism includes toxic diffuse goiter (Graves disease). autonomous functioning nodular goite

3、r (Plummer disease).,1. Radioiodine Therapy of Hyperthyroidism,The therapeutic approaches to hyperthyroidism areablation of peripheral tissueblockade of new hormone synthesis inhibition of the peripheral effects of the hormone and/or conversion of T4 to T3.Treatment modalities include radioiodine, d

4、rug therapy (thionamides, iodine, and beta blockers), and surgery. The actual therapy selected on the characteristics of the individual patient and the underlying cause of hyperthyroidism.,The comparison of hyperthyroidism in 3 kinds of treatments,Iodine-131 is the only radioisotope still used for t

5、he therapy of thyroid disease. It ablates thyroid tissue by selectively localizing in hyperfunctioning thyroid tissue. The iodine atom is actively trapped and organified onto tyrosine contained in intrathyrodial thyroglobulin. Iodine-131 emits a beta particle with mean energy of 0.19 Mev (macimum,0.

6、81 Mev), an average path range of 0.8 to 1mm.,1.1 Principle,When iodine-131 localized in hyperfunctioning cells, beta particle can alter or destroy cell, finally cause focal fibrosis by resulting from ionization and excitation of nuclear DNA. Thereby, aim to destroy enough hyperfunctioning thyroid t

7、issue and restore to euthyroidism.,1.2 Indication1. Patients who are Graves disease with moderate symptom and signs, age above 25 years.2. Patients who are poor surgical risks or refuse to operation.3. Patients who have recurrence following surgical or medical therapy.4. Patients who are not effect

8、or allergic to antithyroid drugs.5. Patients whose effective half time of 131I in thyroid is over 3 days.,1. Patients who have severe hyperthyroidism.2. Patients whose leucocyte count is below 3.0109/L, or Plt count 80109/L3. Patients whose effective half time of 131I in thyroid is less than 3 ds.,1

9、.3 Relative Contraindication,1. Patients who are in pregnancy and Lactation2. Patients who have large goiter with press syndrome and sign3. Patients who have severe hepatic and renal insufficiency4. Patients who have hyperthyroidism complicated with recent myocardial infarction,1.4 Absolute Contrain

10、dication,Patient Preparation 1. Patients should discontinue iodine containing drug and food affecting the thyroid uptake before treatment, same as the RAIU. 2. Patients should undergo RAIU test and determine the effective T1/2 of 131I. 3. Estimate the weight of the thyroid gland usually by palpation

11、 (or more accurately by ultrasound). 4. Patients can be treated with beta receptor blockers if necessary.,1.5 Method,The selection of an appropriate dose of 131I is essential to avoid undertreatment (resulting in persistent or recurrent hyperthyroidism ) or overtreatment (which can progress to perma

12、nent hypothyroidism ). The following formula is convenient for dose calculation.131I(Ci)=(estimated weight of thyroid gland in grams100 Ci/g)/(MAX% uptake of thyroid)The selection of 100 Ci/g is based on an estimate of the desired absorbed radiation dose. Iodine 131I may be given in liquid or capsul

13、e form. The traditional approach advocates the administration of 7000 to 10000 rad to the thyroid.,Selection of Therapeutic Dose,Other factors affecting the efficacy of this dose include the thyroid biologic halftime of 131I,which can change with drugs or diet, and the radiation sensitivity of the t

14、hyroid gland, which cannot be readily estimated. If it requires a second, third, or more doses, retreatment should not be considered for at least 6 months.,1.6 Adverse ReactionDuring early period of 131I treatment, there are no significant side effects. Sometimes just a mild gastrointestinal reactio

15、n, and no special treatment is required. It is generally accepted that hypothyroidism is inevitable in patients with Graves disease treated with 131I.,Various studies have shown that patients became hypothyroid 1 year after treatment and that the incidence of hypothyroidism is approximately 3% to 5%

16、 each year. But delayed hypothyroidism develops at the same rate (after 1 year) regardless of initial dose.,With our present inability to predict when hypothyroidism will occure, it is crucial that the patient receives annual posttreatment follow-up so that hypothyroidism can be readily diagnosed an

17、d treated. Fifty years of experience with 131I treatment has shown no increase in the incidence of thyroid cancer, leukemia ,or other malignancies. No proved adverse genetic defects have been noted in children whose parents previously were treated with 131I.,1.7 Evaluation of Therapeutic Effect,In g

18、eneral, there was no clinical response for 3 to 4 weeks after 131I treatment. The maximum effect is usually seen in 3 to 4 months. The patients may be seen the improvement of symptom and sign, which include the fall of T3 and T4 level in serum. In order to obtain more rapid control, adjunctive drug

19、administration may be used, for example, propranolol 40mg q.i.d. 80%-90% of patients no longer have hyperthyroidism after a single dose.,Thyroid carcinomas are classified by the World Health Organization as papillary (70% to 80%), follicular (15%), medullary (5% to 10%), and undifferentiated or anap

20、lastic (5%). Well-differentiated papillary and follicular carcinomas are slow-growing and carry a relatively good prognosis.,2 Radioiodine Therapy of Thyroid Carcinoma,While poorly differentiated medullary and anaplastic carcinomas are aggressive with a poor prognosis. Papillary carcinomas are more

21、likely to be found in regional nodes than follicular carcinomas, but follicular tumors are more often distantly metastatic than papillary carcinoma.,2.1 Ablation of Normal Thyroid Gland Remnant,Following total thyroidectomy, one must ascertain that there are no thyroid tissue remnants after surgery

22、and that there are no occult metastases.,Implication of Ablation of Residual Tissue,Thyroid cancer tends to be multifocal, and any remnants of the thyroid gland could contain malignancy Occult tumor may be found and killed with an ablation dose If one removes all functioning tissue ,one can use seru

23、m thyroglobulin level later as a diagnostic test to monitor recurrence,Normal thyroid tissue has a significantly greater affinity for iodine than functioning thyroid carcinoma, and so detection and treatment of carcinoma are difficult as long as normal tissue is allowed to persistHormone secretion b

24、y 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,1.Patients who are in pregnancy and lactation

25、2.Patients who are below 3.0*109/L of leucocyte count or with severe hepatic and renal insufficiency3.Patients who are poorly differentiated thyroid carcinoma or with no affinity for iodine in focus.,Method,The administration of the postoperative diagnostic dose of 131I to detect any thyroid remnant

26、 is performed 4 to 6 weeks after thyroidectomy, because at this time the serum TSH level exceeds 30 mIU, a level that stimulates iodine uptake in residual thyroid tissue.Routinely, administer an ablative dose of 100 mCi or a dose of 150-250 mCi with detected functional metastases in some sites.,Whol

27、e body 131I scan performed 1-2 week after ablation .One has a greater chance of visualizing functioning metastases as well as remnants of the thyroid gland. Ablation of residual postsurgical thyroid gland or tumor with 131I is very difficult if a significant amount of functioning tissue remains. Fur

28、thermore, radiation thyroiditis is a likely result. Multiple small iodine doses would be required over a relatively long time to avoid this complication.,Method,2.2 Treatment of Metastatic Thyroid Carcinoma,IndicationPatients with well-differentiated thyroid carcinoma who have recurrence and residua

29、l 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,1. Patients w

30、ho are in pregnancy and lactation.2. Patients whose leucocyte count are below 3.0109/L or with severe hepatic and renal insufficiency.,Selection of Therapeutic Dose,The treatment for functioning metastatic thyroid carcinoma must balance the need for a cytocidal tumor dose against side effects produc

31、ed in healthy tissue by such a dose. Inadequate treatment could simply reduce the iodine concentration ability of metastases, reducing effectiveness of future therapy, without leading to tumor sterilization.,When the radiation dose to metastatic lesions exceeded 8 000 rads, 98% of lesions responded

32、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 metastase, 175 to 200 mCi for pulmonary metastases, and 200 mCi for skeletal metastatic disease.,Selection of Therapeutic Dose,This

33、radioisotope is often supplied as a solution of sodium iodide and, especially with a low pH, is volatile. Therefore the manipulation of 131I should be performed in a fume hood with the exhaust fan. All iodine vials must be handled behind lead glass shielding with long handle tongs, and then kept in

34、lead containers.,2.3 Radiation Safety with Iodine-131,Hospitalized patients remain in a single room and are monitored one to two times daily for radiation burden, Saving urine for counting purpose can lead to contaminating spills. and this is not a recommended safety technique. No restrictions are r

35、equired when the average exposure rate measures 2 mR/hr at any distance.,2.3 Radiation Safety with Iodine-131,1. Cytopenia；2. Radiation pneumonitis；3. Acute and/or chronic sialadenitis；4. Gastrointestinal radiation is not uncommon, begins about 4 to 12 hours after 131I administration, has a prevalen

36、ce of 50% to 70%,and generally resolved by 36 hours, probably related to the intestinal concentration of 131I.,2.4 Side Effect of 131I Therapy,Autonomously functioning thyroid adenoma,Bone metastasis is a common sequela of solid malignant tumors such as prostate, breast, lung and renal cancers, whic

37、h can lead to various complications, including fracture, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. The use of conventional radiography and bone scanning helps confirm the presence of bone metastasis but can also assess the extent.,3. Radionuclide Therap

38、y of Bone Metastasis,Classify the lesions into predominantly osteoblastic , or mixed type; and, finally, Stratify those lesions that are at risk for fracture or cord compression. The treatment of bone pain from metastases remain palliative at present, and can consist of systemic analgesics, antitumo

39、r agents, hormones, chemotherapy, steroids, local surgery, anesthesia, and external beam radiation.,3. Radionuclide Therapy of Bone Metastasis,In general, no single method will keep the patient free of symptoms for an extended period of time, and usually a combination of systemic and local modalitie

40、s may be required. Systemically administered radiopharmaceuticals offer the advantage of wide applicability in an outpatient setting. Injection of the radiopharmaceuticals are easily administered without the need for expensive high-technology equipment.,3. Radionuclide Therapy of Bone Metastasis,3.1

41、 Principle and Agents,Several radiopharmaceuticals for treating painful bone metastases have been developed, The physical characteristics of these radionuclides vary, and each confers certain benefits. Most of these agents are administered intravenously and target the painful bone metastses by accre

42、tion to the reactive bone sites with a high target to non-target tissue ratio and a very low concentration in the surrounding normal bone, underlying bone marrow, or other structure.,The characteristics of the emissions (, internal conversion, or Auger electrons) determine the therapeutic suitabilit

43、y of the radionuclide because the range of penetration is related to the energy of the emitted particles. At present, radiopharmaceutical for systematic radioisotope therapy include Strontium-89, Phosphorous-32, Samarium-153 and so on.,3.1 Principle and Agents,3.2 Indication,1.Patients who have bone

44、 metastases proved by clinical, X-rays and skeletal imaging. It is better for multifoci bone metastasis and bone metastasis resulted from prostate, breast and lung.2.Patients who have severe bone pain resulted from bone metastasis. Other treatment has no effect.3.Patient who are above 3.5109/L of le

45、ucocyte count, and Plt80109/L,3.3 Contraindication,1. Patient who have osteolytic cold region in skeletal imaging.2. Patient who are below 3.0 109/L of leucocyte count or severe hepatic and renal insufficiency.,3.4 Dose,Single injections of the systemic radioisotope, given over 2-3 min, reach all os

46、teoblastic bone metastases, regardless of whether they are symptomatic or asymptomatic. In addition to targeting lesions that are predominantly osteoblastic, they also target lesions that are mixed and have both osteolytic and osteoblastic components.,More than half of the patients who are treated o

47、btain relief of pain, thus reducing their need for analgesics and improving the quality of life and mobility. Relief of pain may be achieved within 2-7d depending on the agent and may last several months after a single injection.,3.4 Dose,Serial injections may be given if response is partial or if s

48、ymptoms return after appropriate recovery of the bone marrow, The dose of 153Sm-EDTMP is from 0.8 to 1.2 mCi/kg. The patients received 30-40mCi/kg with 89Sr. Patients receiving 2 or more doses received a little more dose for all subsequent treatments.,3.4 Dose,3.5 Evaluation,The goal of systemic rad

49、ioisotope 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 li

50、fe of cancer patients with bone pain.,Future consideration for systemic metabolic radiotherapy includes their use at an earlier stage in high-risk patients who are likely to develop bone metastasis to prevent this from occurring. With some of the newer, short-lived agents, high dose levels can be administered over short periods of time with subsequent minimal residual radioactivity in the bone, allowing reinstitution of chemotherapy at an earlier stage.,