Diagnostic Uses of Radiopharmaceuticals

Radiopharmaceuticals and Imaging • I-Orthoiodohippurate (Hippuran) – 88% extraction efficiency first hour – plasma clearance t1/2 30 min – peak value 3-5 min (t1/2 of 7-10 min) • Renogram – arrival of tracer (vascular phase) 30 s – renal accumulation – excretion Renogram • Second and third phases important – diagnosis of obstructive disease of kidneys • Renal Transit time (3-5 min in normals) – the period between injection and peak renal activity – if prolonged (2nd phase less step) • renal arterial stenosis, dehydration, pooling in renal pelvis – Excretory phase • state of dehydration, capacity of renal pelivs or obstructive tubular abnormality (acute tubular necrosis and ureteral obstruction due to stensois Renogram • If obstruction is noted – Lasix • if excretory obstruction becomes normal • if obstruction is mechanical (calculus) little change 99mTc-MAG3 • High radiation dose from Hippuran • plasma clearance is effective renal renal plasma flow • used for function studies of the kidneys • favored agened Effective Renal Plasma Flow (ERPF) • Is the rate of plasma flow irrespective if filtered or secreted. – Both hippuran and MAG3 are used • Two methods – constant infusion method – single injection • In obstructive diseases the values is smaller due to decease urine flow 99mTc-DTPA • 100% filtered • Used to measure GFR 99mTc-Glucepate • Filtered and secreted • plasma clearance few minutes • see renal parenchyma first followed by pelvis • 99mTc-DMSA – filtered and secreted – t1/2 10 min >glucepate – lower amounts needed Captopril Renography • Renal Artery Stenosis – give captopril • decrease in uptake of Tc-DTPA • accumulation of MAG3 hippuran Skeleton • Hydroxapatite cyrstal – calcium phosphate, carbonate hydroxide – Accretion ? • Radiopharmaceuticals – Phosphonate, Phosphate • HEDP, PYP, MDP, HDP • plasma clearance 3-4 min Skeleton • Cellullitis and Osteomyleitis – three phase bone scan • hyperemia in celllulits (flow and pool, delayed in uptake) • Osteomyleitis – increase in all three phases Mechanisms of Uptake • Hydroxyapatite uptake – hydroxapatite crystal removes the phosphonate compounds, thus setting the reduced Tc free to bind to the crystal • collagen uptake – Tc phosphonate complexes localize both inorganic and organic matrices of bone • Diagnosis – metastiatc lesion, Paget, fracture, osteomyleitis, bone tumor, rheumatoid arthritis Bone Marrow • Makes RBC • Iron binding and TIBC, transferrin • Tc-Colloids – <100 nm • 111In-chloride (aplastic anemia) • Diagnosis – muliple myeloma, myelofibrosis (decreased uptake) – increased (polycythemia vera, hemolytic anemia) Heart Radiopharmaceuticals • Perfusion Imaging – 210-Tl (Thallous Chloride) • • • • • • • • • mimics K low energy use resting and exercise imaging planar and SPECT uptake is blood flow dependent normal tissue gets more blood flow more signal ishemic tissue gets less wash out period different also Persantine & adenosine, and aminiophylline Tc-Sestambi (Cardiolite) • • • • • Liophilic monoion accumulates passive diffusion accumulates in mitochondria redistribution ? Lots of liver uptake ( give fatty meals milk before?) Cardiolyte Case Case Case Adrenal Gland Imaging • 2 glands, endocrine, central medulla, outer cortex Diseases Addison’s Disease Cushing Disease Pheochromocytomas Adrenal Agents • 131-I-NP-59 – NP-59 is a cholesterol analog which will localize to adrenal cortical lesions such as adrenal adenomas. It is most useful in the evaluation of incidentally detected adrenal masses and hyperaldosteronism. The examination is less useful in the evaluation of Cushings syndrome, which is most commonly due to bilateral adrenal hyperplasia – Dexamethasone suppression exam • 131-I-MIBG • Structurally, MIBG resembles norepinephrine and guanethidine (a neurosecretory granule depleting agent). MIBG images the adrenal medulla (NOT the adrenal cortex) and sympathetic nervous tissue • Good for phenochromocytomas TUMOR IMAGING • 67-Ga Citrate – – – – behaves like iron transferrin or not? Secreted in large intestine common agent Gallium Scan : This patient is a 32 year old male with recently diagnosed Hodgkin's Disease. The patient has not yet undergone therapy. Bone Scan Radiolabeled Antibodies • Mab • In vivo deiodination using 111-In but 111 In accumlates in liver sometimes • 111In-Capromab Pendetide (ProstaScit) – cleansing enema • 111In-Satumomab Pendetide (OncoScint CR/OV) • 99m-Tc-Arcitumomab (CEA-Scan) (Fab) • 99m-Tc-Nofetumomab (Merpentam) Fab lung ca A 76-year-old male with a prior history of metastatic prostate cancer was diagnosed with colon cancer with liver metastases. Diagnosis was based on a CT scan and a subsequent liver biopsy. Following the biopsy, the patient developed increasing discomfort in the right lower quadrant with a palpable mass. A barium enema showed a large annular lesion in the cecum, and palliative resection was scheduled to prevent obstruction. A CEA Scan was performed prior to surgery Other Agents • 99mTc-Sestamibi – accumulates non-specifically in various tumors such as breast • 201-Thallous Chloride – brain tumors, • 18F-FDG – various tumors • 111-In-penteteotide – somatostatin analog, metastatic neuroendocrine tumors Thrombus Detection • There is a pink to red recent thrombosis in this narrowed coronary artery. The open, needle-like spaces in the atheromatous plaque are cholesterol clefts AcuTect is a unique, synthetic peptide radiopharmaceutical with a mechanism of action dependent on the disease process.12 Based on in vitro and in vivo animal data, not confirmed clinically, AcuTect binds preferentially to the glycoprotein (GP) IIb/IIIa receptors found on activated platelets • Therapeutic Uses of Radiopharmaceticals • Hyperthyrodism – – – – – – – treatments (drugs, thyroidectomy, 131-I) 131-I (90% negatrons) dose 3-7 mCi second treatment in about 25-30% not used in pregnant woment Graves disease Plummer’s disease Plummer's disease • also called Toxic Multinodular Goitre, thyroid condition characterized by marked enlargement of the thyroid gland (goitre), firm thyroid nodules, and mild overproduction of thyroid hormone (hyperthyroidism). Plummer's disease, which usually occurs in older people, is of unknown etiology. Its symptoms resemble those of Graves' disease, a condition believed to be an autoimmune disorder caused by Plummer’s Disease Thyroid Cancer • Well-differentiated thyroid cancers – papillary and follicular – anaplastic and medullary • Lithium Carbonate • Lithium suppresses the release of thyroid hormone from thyroid tissue and has been found to prolong the biologic T1/2 of I-131 especially in tumors with biologic half-lives of less than 6 days, with little effect on whole body exposure. When given for 1 week prior to therapy, it may serve to increase the radiation dose delivered to functioning thyroid tissue • http://www.mamc.amedd.army.mil/williams /NucMed/THY10.htm Papillary Thyroid Peak onset ages 30 through 50 Females more common than males by 3 to 1 ratio Prognosis directly related to tumor size [less than 1.5 cm (1/2 inch) good prognosis] Accounts for 85% of thyroid cancers due to radiation exposure Spread to lymph nodes of the neck present in more than 50% of cases Distant spread (to lungs or bones) is very uncommon Overall cure rate very high (near 100% for small lesions in young patients Characteristics of Follicular Thyroid Cancer • Peak onset ages 40 through 60 Females more common than males by 3 to 1 ratio Prognosis directly related to tumor size [less than 1.0 cm (3/8 inch) good prognosis] Rarely associated with radiation exposure Spread to lymph nodes is uncommon (~10%) Invasion into vascular structures (veins and arteries) within the thyroid gland is common Distant spread (to lungs or bones) is uncommon, but more common than with papillary cancer Overall cure rate high (near 95% for small lesions in young patients), decreases with advanced age Characteristics of Medullary Thyroid Cancer • Occurs in 4 clinical settings (see below), can be associated with other • endocrine tumors Females more common than males (except for inherited cancers) Regional metastases (spread to neck lymph nodes) occurs early in the course of the disease Spread to distant organs (metastasis) occurs late and can be to the liver, bone, brain, and adrenal medulla Not associated with radiation exposure • Usually originates in the upper central lobe of the thyroid Poor prognostic factors include age >50, male, distant spread (metastases), and MEN II-B Residual disease (following surgery) or recurrence can be detected by measuring calcitonin Characteristics of Anaplastic Thyroid Cancer • Peak onset age 65 and older Very rare in young patients Males more common than females by 2 to 1 ratio Typically presents as rapidly growing neck mass Can occur many years after radiation exposure Spread to lymph nodes of the neck present in more than 90% of cases Distant spread (to lungs or bones) is very common even when first diagnosed Overall cure rate very low Indications • Near-total thyroidectomy spares the posterior capsule on the side contralateral to the carcinoma in an attempt to preserve parathyroid tissue. Ablation therapy with I-131 is performed for the following indications: • * To destroy the small amount of thyroid tissue remining in the neck after surgery • * Residual neck bed activity with an I-131 uptake greater than 0.5% • * For the treatment of functional metastases • * Possibly for the treatment of patients with elevated thyroglobulin levels, but a negative I-131 scan Treatment of 131 I • • • • • Acute pain tenderness anorexia, nausea maybe bone marrow suppression high doses sialadenitis (10%) Bone Pain • http://www.snm.org/pdf/ther2.pdf • common complication – drugs, external radiation, internal radiation • Agents – 32-P Orthophosphate • • • • • half life of 14.2 days, 1.7 Mev negatron 6-12 mCi given IV Pretreat with androgen response rate 80% (for about 6 months) bone marrow suppression, Quardramet (153Sm-EDTMP • Negatron emitter, 0.81MeV, t1/2 1.9days gamma photon 103 keV • dose 1 mCi/kg • 65% patients have relief • may last up to a year • myelotoxicity • Quadramet® is a unique radiopharmaceutical that is administered as a single injection and can be given on an outpatient basis • Causes minimal exposure to normal tissue (average beta particle penetration is 1.7 mm in bone and 3.1 mm in soft tissue)1 Metastron (89-Sr Cl • • • • • • Negatron, 1.43 MeV, t1/2 50.6 days, dose = 4 mCi mylosupression remission up to 20% can treat every 6 months initial increase in pain for 3 days then decreases • Strontium-89 decays by beta emission with a physical half-life of 50.5 days. The maximum beta energy is 1.463 MeV (100%). The maximum range of ß- from Strontium-89 in tissue is approximately 8 mm • Following intravenous injection, soluble strontium compounds behave like their calcium analogs, clearing rapidly from the blood and selectively localizing in bone mineral. Uptake of strontium by bone occurs preferentially in sites of active osteogenesis; thus primary bone tumors and areas of metastatic involvement (blastic lesions) can accumulate significantly greater 186Re-HEDP • http://www.eanmrtc.org/Protocol/prebone.ht m#Precautions • negatron, t1/2 3.8days, 1.07 Mev, gamma photon 137 kev • 186Re HEDP is excreted predominantly via the kidneys although some faecal excretion does occur. The patient should be advised to observe rigorous hygiene for the first two days after administration. Patients judged to be at risk of urinary incontinence should be catheterised immediately prior to radiopharmaceutical injection and remain on catheter drainage for 3 to 5 days. Appropriate advice regarding contact with others should be given in accordance with local regulations. Polycythemia Vera • Polycythemia is a condition of increased production of red blood cells (RBCs). The percentage of RBCs in the blood may become so high that the blood ceases to flow in some smaller vessels and capillaries. In this photomicrograph, the RBCs are densely packed together 32-P sodium phosphate evaluate 12 weeks second treatment sometimes Leukemia • What is it? • Types • radioactive treatment – 32P given weekly until the WBC count is sufficiently decreased. Life expectancy does not increase to a large extent by this treatment. A C M L Malignant Effusion in Pleural and Peritoneal Cavities • 32P chromic phosphate colloid