Radiopharmaceuticals for Liver, Spleen, GI System

  1. Liver
    1. The principle types of radiopharmaceuticals used to study the liver include
      1. Particulate agents (radiocolloids) – trapped within the liver sinusoids (containing Kupffer’s cells) permitting morphologic evaluation of the liver.
      2. b. Hepatobiliary agents – undergo hepatocyte (polygonal cell) extraction and excretion into bile, permitting functional assessment of the liver.
    2. Particulate agents (Tc-99m Sulfur Colloid)
      1. Compounding - Tc-99m sulfur colloid is a sterile colloidal dispersion of sulfur particles labeled with Tc-99m and prepared from a kit. The kit consists of:
        1. A reaction vial containing a lyophilized mixture of 2.0 mg anhydrous sodium thiosulfate (source of sulfur), 2.3 mg disodium edetate (Al +3 ion chelator), 18.1 mg gelatin (protective colloid that controls particle size).
        2. A Solution Vial A with 1.8 mL 0.14 M HCl
        3. A solution B vial containing 1.8 mL with 24.6 mg/mL anhydrous sodium biphosphate and 7.9 mg/mL sodium hydroxide (buffer).
      1. The kit is stored at 15 - 30 °C.
      2. The kit is prepared by:
        1. Adding 1 – 3 mL Tc-99m sodium pertechnetate (NMT 500 mCi/mL) to the reaction vial.
        2. After addition of 1.5 mL of Vial A, the reaction vial is placed in a boiling water bath for 5 m. The vial is cooled and 1.5 mL Vial B is added.
        3. The pH of the dispersion is 4.5 – 7.5. Radiochemical purity must be 92% or higher. The labeled product is stable for 6h and stored at 15 – 30 °C.

      3. EDTA chelates any aluminum ion present in Tc-99m sodium pertechnetate solution. Free aluminum ion reacts with the phosphate buffer to form insoluble aluminum phosphate also carrier Tc-99m SC binds with this product.
      4. This tpye of percipiate is known as flocculation. If injected into a patient would cause uptake in the lungs and liver (pending particle size).
    3. Clinical use
      1. Imaging the RES
        1. Liver/spleen imaging
        2. Space occupying lesioins are identified
        3. Colloidal Shift
        4. 1 – 8 mCi is administered IV
      2. For bone marrow stusies 3 – 12 mCi is given
      3. Evaluation of peritoneovenous ( LeVeen) patentcy shunts
      4. Esophageal transit studies
      5. Gastroesophageal reflux studies
      6. Pulmonary aspiration studies
      7. Lymphoscintigraphy.
    4. Localization
      1. Phagocytosis of small colloids particles that range from 1.0 to 0.1 μm
      2. Primarily uptake occurs by the Kupffer’s cells in the liver
      3. Larger particles become trapped in the within liver sinusoids
    5. Biodistribution: Tc-99m SC rapidly clears the blood
      1. Five to 15 minutes in normal pateints
      2. Localizes in liver (85%), spleen (4- 8 %) and bone marrow (remainder).
      3. Factors that effect clearance from blood and biodistribution include:
        1. Blood flow – Volume of blood flow through an organ
        2. Disease state – Liver disease (i.e., cirrhosis) shifts radiocolloid localization to other RES organs.
        3. Particle size – Thiosulfate-generated particles demonstrate particle size distribution as follows: less than 0.1 μm, 15%, less than 0.4 μm, 70%, 0.1 – 1.0 μm, 80% and greater than 1.0 μm, 5%. Larger particles localize in liver and spleen while smaller particles localize in bone marrow.
    6. Opsonization – Ability of the opsonins in blood to coat particles for recognition by the RES.
    7. Excretion – By 92 h 4% and 3% of radiopharmaceutical is excreted in urine and feces, respectively.
  • Hepatobiliary Agent
    1. Chemical name - Tc-99m Mebrofenin [BRIDA] Choletec ( 2 ,4,6,-trimethyl, 5- BRomoacetanilido- Imino Diacetic Acid)
    2. Compounding
      1. A sterile aqueous solution prepared from a lyophilized kit sealed under nitrogen containing the complexing ligand mebrofenin (45 mg), stannous fluoride dihydrate (1.03 mg), and methylparaben (5.2 mg) and propylparaben (0.58 mg) as preservatives.
      2. The pH of the reconstituted product is 4.2 – 5.7. The kit is stored before and after labeling at 20 – 25 °C.
      3. The kit is prepared by adding up to 100 mCi in 1 – 5 mL Tc-99m sodium pertechnetate and allowing it to stand at room temperature for 15 minutes.
      4. The labeled product is stable for 18 hours because it contains a preservative. The radiochemical purity of the complex should be 90% or greater.
    3. Chemical name - Tc-99m Disofenin Injection [ DISIDA] Hepatolite (Chemical name – 2 ,6- Di ISopropylacetanilido- Imino Diacetic Acid)
    4. Compounding
      1. A sterile aqueous solution prepared from a lyophilized kit containing the complexing ligand Disofenin (20 mg) and stannous chloride dihydrate (0.6 mg) at pH 4 –5, sealed under nitrogen.
      2. The kit is stored at 15 – 25 °C before and after labeling.
      3. The kit is prepared by adding 12 to 100 mCi in 4 –5 mL Tc-99m sodium pertechnetate. The vial is swirled for 1 m and allowed to incubate at RT for 4 m. The labeled product is stable for 6 hours.
      4. The radiochemical purity of the complex should be 90% or greater.
    5. Clinical use
      1. Hepatobiliary imaging using 2 – 5 mCi in nonjaundice patients and up to 10 mCi in patients with bilirubin levels greater than 1.5 mg/dL.
      2. Since bilirubin competes with HIDA analogues for the hepatocyte transporter, the following dosage scheme in patients with elevated bilirubin has been recommended:

        3. 2 mgdL – 5 mCi
        2 – 10 mg/dL – 7.5 mCi
        >10 mg/dL – 10 mCi.

      3. Lidofenin is effective up to 5 mg/dL bilirubin whereas disofenin and mebrofenin are effective at higher levels.
      4. Mebrofenin is less affected by bilirubin than disofenin.
        1. At 10 mg/dl bilirubin in isolated rat hepatocytes, uptake of disofenin and mebrofenin decreased to 36% and 71%, respectively.
        2. Therefore, mebrofenin should be more effective in patients with reduced hepatocellular function.
    6. Localization – Active transport via the anionic site on the hepatocyte membrane.
    7. Biodistribution
      1. Following iv administration of either Tc-99m disofenin or Tc-99m mebrofenin , liver uptake in normal individuals is evident within 5 m and peaks at 10 m.
      2. Gallbladder visualization occurs within 10 – 15 m and peaks at 30 – 60 m. Intestinal activity is seen at this time.
      3. The normal structures seen sequentially are liver parenchyma, hepatic ducts, common bile duct, gallbladder, and intestine.
    8. Diseases
      1. In acute cholecystitis, gallbladder activity is absent.
      2. In chronic cholecystitis, the appearance of gallbladder activity may be delayed for several hours.
      3. When the common bile duct is obstructed with gallstones, radiotracer activity clears slowly from the blood, liver uptake is decreased and its clearance delayed, and kidney activity is evident.
  • SPLEEN
    1. The principal types of radiopharmaceuticals used to study the spleen are:
      1. Radiocolloids, which are localized by splenic phagocytes
      2. Denatured radiolabeled red blood cells (RBCs)
    2. Heat-Denatured Tc-99m Red Blood Cells
      1. Compounding - Red cells radiolabeled by the Ultra-tag RBC kit are mixed with saline and heated for 15 m at 49 – 50 °C.
      2. Clinical use – Accessory spleen (1 mCi)
      3. Localization – Cell sequestration. Heating RBCs changes their shape from normal biconcave disks to spherocytes. Weakened and fragile cells squeeze through 3 μm pores in the cords of red pulp, are lysed, and release their radioactive contents within the spleen.
      4. Insufficient heating results in decreased sequestration by the spleen while over heating causes hepatic uptake due to cell lysis in the bloodstream.
      5. Biodistribution – Labeled heat-denatured RBCs rapidly clear the blood (T1/2 = 6.3 m), and splenic uptake reaches a plateau in 30 m. Mean uptake is 72% of i.d.
      6. Excretion – 5% of i.d. is excreted in the urine at 2 h.
  • GASTROINTESTINAL STUDIES
    1. Gastrointestinal reflux – Tc-99m SC
    2. Gastric Emptying - Liquid markers: In-111 DTPA (100 μCi), Tc-99m DTPA, Tc-99m SC
    3. Solid markers: Tc-99m SC in scrambled egg (1 mCi)
    4. GI Bleeding
      1. Tc-99m SC (during active bleeding)
      2. Tc-99m RBCs (agent of choice)
    5. Meckel’s Diverticulum – Tc-99m sodium pertechnetate
    6. GI Protein loss - Cr-51 chloride

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