Tc-Pertechnetate

The Tc eluate used for radiolabeling must comply with the specifications stated in the pharmacopeia. Additionally, the specific activity (activity/Tc carrier) and the activity concentration (activity/ml) should be known. 

Since the specific activity of the Tc eluate is related to the time elapsed between elutions, daily elution of the generator at an interval of 24 h will produce eluates with the best quality. Kits are compatible with eluates from different commercial generators however, high specific activity is mandatory with some kits, especially when labeling biomolecules. 

The total Tc activity and the volume injected into the vial (kit) should comply with the recommendations by the manufacturer. Dilutions should be performed with isotonic saline. 

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There are three general types of radiopharmaceuticals elemental radionucHdes or simple compounds, radionucHde complexes, and radiolabeled biologically active molecules. Among the first type are radionucHdes in their elemental form such as Kr and Xe or Xe, and simple aqueous radionucHde solutions such as or I-iodide, Tl-thaUous chloride, Rb-mbidium(I) chloride [14391-63-0] Sr-strontium(II) chloride, and Tc-pertechnetate. These radiopharmaceuticals are either used as obtained from the manufacturer in a unit dose, ie, one dose for one patient, or dispensed at the hospital from a stock solution that is obtained as needed from a chromatographic generator provided by the manufacturer. 

Many kits contain the indicated biologically active ingredient in a lyophilized form with stannous chloride. A Tc-labeled radiopharmaceutical, which can be used for six hours, is formed when mixed with Tc pertechnetate. Preparation of the agent is at room temperature, unless otherwise stated. Technetium-99m. Available Tc kits are Hsted below. 

Technetium-99m disofenin is used for hepatobiliary imaging. Disofenin (2,6-diisopropylphenylcarbamoyhnethyliminodiacetic acid) is the active ingredient. Product formation is accompHshed by addition of up to 3.7 GBq (100 mCi) of Tc pertechnetate. 

Technetium-99m albumin coUoid is cleared by the reticuloendothehal (RE) cells and is used for visualization of the RE system of the Hver, spleen, and bone marrow. The product is formed by the addition of up to 2.8 GBq (75 mCi) of Tc pertechnetate. 

Technetium-99m mertiatide (A/-[Ai-[A/-[(benzoylthio)acetyl]glycyl]glycine) is a renal imaging agent. It is excreted by the kidneys via active tubular secretion and glomerular filtration. The kit vial is reconstituted by using 740—3700 MBq (20—100 mCi) of Tc pertechnetate and boiling for 10 minutes. 

The corresponding radiopharmaceutical technetium Tc analogue was also prepared by using sodium Tc-pertechnetate instead of sodium perrhenate in Step 3. 

Radiolabelling was carried out by adding 1 mL of 0.2M phosphate buffer at pH7.0 to the freeze-dried kit formulation, followed immediately by addition of 555-740 MBq (1 mL) of Tc-pertechnetate and subsequently by incubation in a boiling water bath for 10 min. 

Figure 2.1.4 shows the structure of a Tc complex with two molecules of penicillamine, confirmed by x-ray crystallography (Franklin et al. 1982). Yet when reduction of Tc-pertechnetate had been performed with SnCl2, a complex with a Tc(IV) oxidation state was reported (Yokoyama et al. 1979). 

Effect of formulation. Kits contain very low amounts of stannous ion for reduction of Tc-pertechnetate nevertheless, SnCl2 is usually in high excess. There are several reasons for using stannous salt in excess. Stannous salts are spontaneously oxidized in air. Also, oxidant species in the eluate may have been formed by radiolysis the amount of Sn(II) available in solution is very low with respect to the total amount of lyophilized SnCl2. In order to assure validity of kits beyond the expiration date, an excess of SnCl2 is used in the kit formulation. 

McAfee JG, Fueger GF, Baggish MS, Holzman GB, Zolle I (1964) Tc-labeled serum albumin for scintillation scanning of the placenta. J Nucl Med 5 936-946 McAfee JG, Fueger GF, Stern HS, Wagner HN Jr, Migita T (1964) ""Tc-pertechnetate for brain scanning. J Nucl Med 5 811-827... 

Electrolytical reduction of Tc-pertechnetate has been investigated (Benjamin 1969, 1970 Dworkin and Gutkowski 1971 Eckelman et al. 1971a Gil et al. 1976). When using zirconium or tin electrodes, anodic dissolution of metal ions produced in situ reduction of pertechnetate (Steigman et al. 1974). Electrolysis has been used as a reliable method for laboratory production of Tc pharmaceuticals. 

The Mo/ Tc generator used in nuclear medicine is based on the chromatographic separation of Tc-pertechnetate. 

Each vial containing Tc-pertechnetate injection solution must have a radioactive label with relevant information ... 

The preparatiou of Tc pharmaceuticals is greatly facilitated by the availability of couunercial cold kits coutaining the chemical ingredients as a lyophilized formulation ready for labeling with Tc-pertechnetate. 

Table 8.1. Variables influencing red blood cell (RBC) labeling with ""Tc-pertechnetate...

Recovery ([REC] i.e., the percentage of injected dose remaining cell bound in the circulation for 60 min) and in vivo biodistribution provide key information about cell integrity and function. Even after several isolation and incubation steps and being exposed to radioactive material, RBC have been shown not to alter their in vivo behavior significantly. Elution of Tc from RBC and/or its poor LE is reflected by gastric secretion of Tc-pertechnetate and accumulation of free pertechnetate in the thyroid, as well as increased urinary radioactivity. 

Table 8.3. Variables influencing platelet labeling with " Tc-pertechnetate...

For determination of the radiochemical purity of Tc pharmaceuticals, methods using standard TLC materials have been described (Zimmer and Pavel 1977). Reversed-phase materials offer advantages with respect to more polar solvents that are miscible with the aqueous medium of the sample (Carpenter 1986). Alumina plates are used to separate anionic Tc-pertechnetate from neutral or positively charged complexes. 

Cellulose. This organic material consists of polymerized glucose fibers (400-500 molecules) in nature and also as a synthetic product (40-200 glucose molecules). Cellulose interacts with water and serves as a stationary phase for the separation of polar substances by paper chromatography. As a powder, it is used as an adsorbent for TLC. Separation of polar substances by paper chromatography is described in the European Pharmacopeia for identification of Tc-pertechnetate (Council of Europe 1982). 

An alternate method is described in (Nickles et al. 1993b). A Mo foil (0.1 mm thick) was used for irradiation and the radiotechnetium was extracted by an electrochemical etching procedure. With the obtained Tc-pertechnetate, Tc-teboroxime was prepared, which was used for the first preliminary human investigation with this " Tc-la-beled pharmaceutical (Nickles et al. 1993 b). Another PET study with Tc-2-methoxy isobutyl isonitrile was also reported (Stone et al. 1994). 

The specific activity of Tc-pertechnetate is not stated in the Pharmacopeia however, it is recommended that the eluate is obtained from a generator that is eluted regularly. 

In vivo labeling of red blood cells (RBC) with sodium Tc-pertechnetate (Callahan et al. 1982) is performed subsequent to pretreatment of RBC in vivo with a stannous reducing agent, using stannous pyrophosphate cold kits (TechneScan PYP, AngioCis) as well as Amerscan Stannous Agent. 

For in vivo RBC labeling, the blood pool scintigraphy should start 10 min after intravenous injection of a bolus of Tc-pertechnetate cardiac dynamic imaging should begin immediately, and abdominal imaging should also begin immediately and at various times up to 24 h. 

Brain scintigraphy 550 MBq, after blocking thyroid and choroid plexus to avoid nonspecific uptake of Tc-pertechnetate... 

Persistent vascular activity of ""Tc-pertechnetate has been observed when scintigraphy has been performed following a bone scan, due to radiolabeled RBC that had retained stannous ions (Ancri et al. 1977 Montelibano et al. 1979). 

Several drugs interfere with the normal biodistribution of Tc-pertechnetate (Hla-dik et al. 1987). Thus, cancer chemotherapeutic agents (methotrexate) can affect brain scintigraphy atropine, isoprenaline, and analgesics interfere in abdominal imaging iodine and other blockers (perchlorate, perrhenate) can modify thyroid uptake. 

Paper Chromatography. The European Pharmacopeia describes descending paper chromatography using methanol/water (80 20 v/v) as solvent developing time is 2 h. The Tc-pertechnetate anion migrates with an Rf value of 0.6. More than 95% of the measured radioactivity corresponds to an Rf of 0.6 less than 5% are detected at the start. 

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