A880IO Ultra-TechneKow" DTE or an altered blood-brain barrier. It also concentrates Ideally, examinations using drug (Technelium Tc 99m Generalor) in the gland, salivary glands, stomach and products - especially those elective in nature - of ~ Rx Only. choroid plexus. After intravenous administration women of childbearing capability should be perfonmed remains in the circulatory system for sufficient time ter during the first ten days following the onset of menses. For the Production of penmit blooe pool, organ perfusion, and major vessel Tc 99m Injection studies. It gradually equilibrates wrth the extracellular Nursing Mothers: Tc 99m IS excreted in human milk DESCRIPTION: space. A fraction is promptly excreted via the kidneys. during lactation, therefore, fonmula-feedings should The Ultra-TechneKow<> DTE Generator is prepared Following the administration of Socium Pertechnetate be subslituted for breast-feedings. with fission-procuced molybdenum Mo 99 adsorbed Tc 99111 as an eye drop, the dnug mixes with tears onto alumina in a lead shielded column. This generator within the conjunctival space. Within seconds to Pediatric Use: provides a closed system for the production of minutes it leaves the conjunctival space and escapes See Indicalions and Usage and Dosage and sterile metastable technetium Tc g9m, which is into the inferior meatus of the nose through the Administration sections. Also see the description produced by the decay of molybcenum Mo 99. nasolacrimal draInage system. During this process of additional risk under Warnings. Sterile. non·pyrogenic isotonic solutions of Sodium the pertechnetate passes through the canaliculi, ADVERSE REACTIONS: Pertechnetate Tc g9m can be obtained conveniently the lacrimal sac and the nasolacrimal duct. In the Allergic reactions including anaphylaxis have been by periodic aseptic elution of the generator. These event of any anatomical or functional blockage of the reported infrequently following the administration of solutions should be clear, colorless, and free from any drainage system there will be a backflow resulting in Socium Pertechnetate Tc 99m. particulate matter. tearing (epiphora). Thus the pertechnetate escapes The carrier-free solution may be used as is, or the conjunctival space in the tears. DOSAGE AND ADMINISTRATION: Sodium Pertechnetate Tc 99m is usually administered diluled to the proper concentration. Over the life While the major part of the pertechnetate escapes of the generator, an elution will contain an amount by intravenous injection, but can be given orally. within a few minutes of normal drainage and tearing, When imaging the nasolacrimal drainage system, of technetium Tc 99m in direct proportion to the it has been documented that there is some degree of instill the SOCium Pertechnetate Tc 99m by the use quantity of Mo 99 decay since the previous elution transconjunctival absorption with turnover of 1.5% of a device such a micropipette or similar method of the generator. The exacl quantity of Tc 99m in the per minute in normal individuals, 2.1 % per minute as which will ensure the accuracy of the dose. eluate is determined by column elution efficiency, in patients without any sac and 2.7% per minute in quantity of Mo 99 on the column, and the elapsed patients with inflamed conjunctiva due to chronic tIme between elutions. For imaging the urinary bladder and ureters (direct --dacPYXystlt~. lndivi ual .-\ia!UC6 ...'":1a~.,:-C.:t-t ,.., - sOlOpte-cystbgraphy);"'me 'oolOrrrt>enecnnetate'-'==~~-~~ Each eluate of the generator should not contain more rates are probably representative and indicate that Tc 99m is administered by direct instillation aseptically than the USP limrt of 0.15 kilobecquerel molybcenum the maximum possible pertechnetate absorbed will into the bladder via a urethral catheter, following Mo 99 per megabecquerel technetium Tc 99m remain below one thousandth of that used in other which the catheter is flushed wrth approximately 200 (0.15 microcurie Mo 99 per millicurie Tc 99m) per routIne diagnostic procedures. mL of sterile saline directly into the bladder. administered dose at the time of administration and INDICATIONS AND USAGE: an aluminum ion concentration of not more than 10 The dosage employed varies with each diagnostic Socium Pertechnetate Tc 99m is used IN ADULTS procedure. If the oral route is elected, the patient micrograms per milliliter of the generator eluate, both as an agent for: of which must be detennined by the user before should fast for at least six (6) hours before and two administration. Brain Imaging (including cerebral radionuclide (2) hours after administration. angiography) The suggested dose ranges employed for various Since the eluate does not contain an antimicrobial Thyroid Imaging diagnostic indications in Ihe average ADULT PATIENT agent, it should not be used after 12 hours from the Salivary Gland Imaging (70 kg) are as follows: time of generator elution. Placenta Localization Blooe Pool Imaging (including radionuclide Vesica-ureteral Physical Characteristics: angiography) imaging: Technetium Tc ggm decays by isomeric transition 18.5 to 37 MBq (0.5 to 1 mCQ Urinary Bladder Imaging (direct isotopic with a physical half-life of 6.02 hours.' The principal cystography) for detection of vesico-ureteral Brain imaging: 37010740 MBq (10 to 20 mCi) photon that is useful for detection and Imaging reflux Thyroid gland studies is listed in Table 1. Nasolacrimal Drainage System Imaging imaging: 37 to 370 MBq (1 to 10 mq Table 1. Principal Radiation Emission Data (dacryoscintigraphy) Salivary gland imaging: 37 to 185 MBq (1 to 5 mq Socium Pertechnetate Tc 99m is used IN PEDIATRIC Mean % Energy Radiation Per PATIENTS as an agent for: Placenta Disintegration (keV) localization: 37 to 111 MBq (1 to 3 mq Brain ImagIng (including cerebral radionuclide Blooe pool imaging: 370 to 1110 MBq (10 to 30 mq Gamma-2 89.07 140.5 angiography) Thyroid Imaging Nasolacrimal Blooe Pool Imaging (inclUding radionuclide drainage system: Maximum dose of 3.7 MBq (1 CX>,JO) External Radiation: angiography) The specific gamma ray constant for technetium Urinary Bladder Imaging (direct isotopic The recommended dosages in PEDIATRIC Te 89m is 0.78 R1hr-mCi at 1 em. The first half-value cystography) for the detection of vesico-ureteral PATIENTS are: layer is 0.017 cm of lead (Pb). A range of values for reflux the relative attenuation of the radiation emitted by this Veslco-ureteral imaging: 18.5 to 37 MBq (0.5 to 1 mq radionuclide that results from interposition of various CONTRAINDtCATIONS: thicknesses of Pb is shown in Table 2. For example, None known. Brain imaging: 5.18 to 10.36 MBq (140 to 280 !-,q the use of 0.25 cm thickness of Pb will attenuate the per kg body weight radiation emitted by a factor of about 1000. WARNINGS: Thyroid gland Radiation risks associated with the use of Sodium imaging: 2.22 to 2.96 MBq (60 to 80 ~q Table 2. Radiation Attenuation by Lead Shielding Pertechnetate Tc 99m are greater in pediatric patients per kg body weight than in adults and, in general, the younger the patient Blooc pool Shield CoeHicient the greater the risk owing to greater absorbed imaging: 5.18 to 1036 MBq (140 to 280 ~ij Thickness (Pb) em of Attenuation radiation doses and longer life expectancy. These per kg body weight greater risks should be taken firmly into account in all 0.017 0.5 benefit risk assessments involVing pediatric patients. Minimum dose of 111 to 185 MBq (3 to 5 mCij 0.08 10" should be employed if radionuclide angiography is 2 Only use generator eluant specified for use with the 0.16 10. perfonmed as part of the brain imaging or blooe pool Ultra-TechneKow'" DTE Generator. Do not use any 10.3 imaging procedures. 0.25 other generator eluant or saline from any other source. 10" 0.33 NOTE: Up to 1 gram of phanmaceutical grade PRECAUTIONS: potassium in a suitable base or capsule Molybdenum Mo 99 decays to technetium Tc 99m As in the use of any radioactive material, care should may be given orally prior to administration of Sodium with a molybdenum Mo 99 half-life of 2.75 days. be taken to minimize radiation exposure to the Pertechnetate Tc 99m for brain imaging, placenta The physical decay characteristics of molybdenum patient consistent with proper patient management localization and blooe pool imaging. When Socium Mo 99 are such Ihat only 88.6% of the decaying and to insure minimum radiation exposure to Pertechnetate Tc 99m is used in pediatric patients molybdenum Mo 99 atoms form technetium Tc occupatlonal workers. for brain or blood pool imaging, administration of 99m. Generator elutions may be made at any time. is especially important to but the amount of technetium Tc 99m available Radiopharmaceutlcals should be used only by minimize the absorbed radiation dose to the thyroid will depend on the interval measured from the physicians who are qualified by training and gland. last elution. ApprOXimately 47% of the maximum experience in the safe use and handling of radionuclides and whose experience and training available technetium Tc 99m is reached after 6 hours The patient dose should be measured by a suitable have been approved by the appropriate government and 95% after 23 hours. To correct for phvsical decav _ radbactivity...ca!lbratkm s~stem !!T'_'TII:>rl;~teJy priOL1!:l.--.. agency autnortzed to license me use of raalonucHdes. of fechnetium Tc 99m, the fractions that remain at administration. selected intervals of time are shown in Table 3. After the termination of the nasolacrimal imaging Parenteral drug products should be inspected procedure, blowing the nose and washing the eyes Table 3. Physical Decay Chart; Technetium visually for particulate matter and discoloration prior with sterile distilled water or an isotonic sodium Tc 99m, Half Life 6.02 Hours to administration whenever solution and container chloride solution will further minimize the radiation permit. The solution to be administered as the patient dose. Fraction Fraction dose should be clear, colorless, and contain no Hours Remaining Hours Remaining Since the eluate does not contpin an antimicrobial particulate matter. agent, it should not be used after 12 hours from time Radiation Dosimetry: O' 1.000 7 0.447 of generator elution. The estimated absorbed radiation doses2 to an 1 0.891 8 0.398 Carcinogenesis, Mutagenesis, average ADULT patient (70 kg) from an intravenous 2 0.794 9 0.355 Impairmenl of Fertility: injection of a maximum dose of 111 0 megabecquerels No long-term animal studies have been performed (30 millicuries) of SOCium Pertechnetate Tc 99m 3 0.708 10 0.316 to evaluate carcinogenic or mutagenic potential or distributed uniformly in the total bocy of subjects 4 0.631 11 0.282 whether Socium Pertechnetate Tc 99m may aHect not pretreated with blocking agents, such as fertility in males or females. pharmaceutical grade potassium perchlorate, are 5 0.562 12 0.251 shown in Table 4. For placental localization studies, Pregnancy Category C: when a maximum dose of 111 megabecquerels (3 6 0.501 Animal reproductive studies have not been conducted millicuries) is used, it is assumed to be uniformly 'Calibration time. with Socium Pertechnetate Tc 99m. It is also not equilibrated between maternal and fetal tissues. known whether Socium Pertechnetate Tc g9m can Clinical Pharmacology: cause fetal harm when administered to a pregnant The estimated absorbed radiation doses to an ADULT The pertechnetate ion distributes In the bOCy similarly woman or can affect reproductive capacity. Sodium patient from the nasolacrimal imaging procedure to the iocide ion but is not organified when trapped in Pertechnetate Tc 99m should be given to pregnant using a maximum dose of 3.7 megabecquerels (100 the thyroid gland. Pertechnetate tends to accumulate women only if the expected benefits to be gained microcuries) of Sodium Pertechnetate Tc 99m are in intracranial lesions with excessive neovascularity clearly outweigh the potential hazards. shown in Table 5. Table 4. Absorbed Radiation Doses From Intravenous Injection (ADULTS) The expiration time of the Sodium Pertechnetate Tc 99m solution is not later than 12 hours after 1110 MBq (30 mCi) Dose 111 MBq time of elution. If the eluate is used to reconstitute Resting Active (3mCi) a kit, the radiolabeled kit should not be used after ULTRA­ Tissue Population Population Dose 12 hours from the time of generator elution or after TECHNEKO~ DTE the expiration time stated on the labeling for the mGy rads mGy rads mGy rads prepared drug, whichever is earlier. (TECHNETIUM Tc 99m GENERATOR) Bladder Wall 15.9 1.59 25.5 2.55 Directions for Use of the Gastrointestinal tract· Technetium Tc 99m Generator: NOTE 1: Immediately upon delivery, the generator 881/895 Stomach wall 75.0 7.50 15.3 1.53 should be placed within a minimum Upper large of one-inch of lead shielding in such 20.4 2.04 36.0 360 intestine wall a manner so as to minimize radiation exposure to attending personnel. Lower large 18.3 1.83 33.0 3.30 NOTE 2: Wear waterproof gloves during intestine wall the elution procedure and during dispensing purposes. NOTE: Molybdenum Red Marrow 5.7 0.57 5.1 0.51 subsequent reconstitution of kits with Mo 99 Breakthrough Limit - The acceptable the eluate. limit is 0.15 kilobecquerel molybdenum Mo Testes 2.7 0.27 2.7 027 99 per megabecquerel technetium Tc 99m NOTE 3: Use a shielded syringe to withdraw Ovaries 6.6 0.66 9.0 0.90 (0.15 microcurie Mo 99 per millicurie Tc 99m) patient dose or to transfer Sodium per administered dose in the Injection, at Thyroid 39.0 3.90 390 3.90 Pertechnetate Tc 99m into mixing vials the time of administration (see USP, Sodium during kit reconstitution. Pertechnetate Tc99m Injection). Brain 4.2 0.42 3.6 0.36 Total Body 4.2 0.42 3.3 0.33 NOTE 4: The needles in the generator are sterile 6. Determine the aluminum ion concentration beneath their covers, and the generator of the eluate. NOTE: Aluminum Ion Placenta 0.5 0.05 has been cleaned underneath the top Breakthrough Limit - The acceptable limit is ~us - - 0.5 0.05 cover. Additional disinfection of these not more than 10 micrograms per milliliter of areas with agents containing alcohol eluate (see USp, Sodium Pertechnetate Tc99m may unfavorably influence the Tc 99m Injection). yield. Table 5. Absorbed Radiation Doses from HOW SUPPLIED: Subsequent Elutions: Dacryoscintigraphy The Ultra-TechneKow" DTE (Technetium Tc 99m) Eluting the generator every 24 hours will provide Repeat steps 1 through 6 of the Elution 3.7 MBq (1 00 ~Ci) Generators contain the following amount of optimal amounts of Sodium Pertechnetate Tc procedure above. Dose of molybdenum Mo 99 at the date and time of 99m. However, the generator may be eluted Sodium Pertechnetate calibration stated on the label. whenever sufficient amounts of technetium Tc Vacuum Loss: Tissue If the vacuum in the collecting vial is lost, do not Tc 99m Catalog No. 99m have accumulated within the column. attempt to re-evacuate the vial, but discard and 881 18.5 gigabecquerels (0.50 curie) mGys rads use a new collecting vial. NDC 0019-9881-01 For Example: Eye Lens: Time After Approximate Yield 882 27.75 gigabecquerels (0.75 curie) EXPIRED GENERATOR DISPOSAL: If lacrimal fluid First ElutioO (hrs.) (% of First Elution) NDC 0019-9882-02 1. Following the life of the generator, remove and turnover is 0.140 0.014 1 10 883 37 9igabecquerels (1.0 curie) dispose of the used TechneStat™ vial and the 16%/min 2 19 NDC 0019-9883-03 eluant vial. If lacrimal fluid 3 27 884 55.5 gigabecquerels (1.5 curies) 2. If appropriate, remove and store the Alignment turnover is 0.022 0.002 4 35 NDC 0019-9884-04 Adaptor for use with replacement generator. 100%lmin 885 74 gigabecquerels (2.0 curies) 5 41 NDC 0019-9865-05 6 47 3. Cover the elution and eluant needles with the If drainage stored needle covers. system ;s 4.020 0.402 686 92.5 gigabecquerels (2.5 curies) blocked NDC 0019-9666-06 Preparation: 4. Close the generator system with its top cover 687 111 9igabecquerels (3.0 curies) Note: The following instructions are applicable by rotating with downward pressure. Total Body' 0.011 0.001 NDC 0019-9667-07 for operation of the Ultra-TechneKow"' DTE Generator with or without the utilization of 5. The intact generator assembly should be either Ovaries· 0.030 0.003 668 129.5 gigabecquerels (3.5 curie) the alignment adaptor. returned to Mallinckrodt Inc. or disposed of in NDC 0019-9668-08 accordance with applicable regulations. Testes' 0.009 0.001 1. Rotate the top cover 30° counterclockwise 889 185 gigabecquerels (5.0 curie) and lift up to remove. NDC 0919-9889-09 This generator is approved for use by persons Thyroid' 0.130 0.013 .L Lift the generator by its handle and position it -890 222 9igabecquerels (6.0 curie) -- .,-,ense9--9~-t-l-je lJ.;,;;;. Nucleel'" Regv!atnr:,' inside the auxiliary shield, aligning the notch Commission to use by-product material identified 'Assuming no blockage of draining system. MIRD NDC 0019-9890-10 in the elution station with the front of the (7.5 curie) in Section 35.200 or under equivalent licenses of Dose Estimate Report No.8, J Nucl. Med., ~~C 0019~~~il?~~abeCqUereIS auxiliary shield. Move the handle so that it is Agreement States. 17: 74-77, 1976. not covering the generator top by pushing it 892 407 gigabecquerels (11.0 curie) off to the side in between the generator and Ultra-TechneKowl!l and TechneStat™ are NDC 0019-9892-12 the auxiliary shield. trademarks of Mallinckrodt Inc. 893 518 gigabecquerels (14.0 curie) 3. Remove the flip-top cap of the eluant vial; In PEDIATRIC patients, the maximum radiation NDC 0019-9893-13 disinfect the stopper, allowing the stopper to Revised 612006 doses when a dose of 185 megabecquerels dry before use. Remove and store the needle 894 592 gigabecquerels (16.0 curie) Mallinckrodt Inc. (5 millicuries) Sodium Pertechnetate Tc 99m is cover from the eluant needles; invert the NDC 0019-9894-14 St. Louis, MO 63134 administered to a neonate (3.5 kg) for brain or eluant vial and push down into place on the 895 703 gigabecquerels (19.0 curie) blood pool ima9ing with radionuclide angiography eluant needles. NDC 0019-9895-15 are shown in Table 6. 4. Place the alignment adaptor onto the top of In pediatric patients, an average 30 minute Each generator is supplied with the following the generator with the raised portion of the exposure to 37 megabecquerels (1 millicurie) of components for the elution of the generator adaptor located over the elution station. Sodium Pertechnetate Te 99m following instillation 7 - Evacuated Collecting Vials, 10 mL. 5. Remove the flip-top cap of the TechneStat™ for direct cystography, results in an estimated Sterile, Non-pyrogenic vial; disinfect the stopper, allowing the stopper absorbed radiation dose of approximately 300 or to dry before use. Secure the TechneStat™ vial micrograys (30 millirads) to the bladder wall and 40 into the TechneStat'M vial shield. 1:IIeD 5 - Evacuated Collecting Vials, 20 mL, to 50 micrograys (4 to 5 millirads) to the 90nads.' 6. Remove and store the needle cover from the Sterile, Non-Pyrogenic elution needle. Place the auxiliary shield lid Healthcare 7 - 70% (v/v) Isopropyl Alcohol Wipes onto the top auxiliary shield ring ensuring Table 6. Absorbed Radiation Doses From 7 - Pressure-sensitive "Caution - Radioactive alignment of the key-hole with the elution Intravenous Injection (PEDIATRIC) Material" collecting vial labels needle. EALLINCKRODT 7 - Pressure-sensitive radioassay data labels 7. Carefully !ower the TechneStat™ vial shield 37 MBq for lead elution shield containing the TechneStat™ vial through the (1 mC,) 185 MBq key-hole, inserting the shielded TechneStat™ Dose (5mCi) Dose 1 - Generator Eluant Vial, 135 mL, Sterile, vial onto the elution needle. Non-Pyrogenic Tissue mGys rads mGys rads or Elution: 1. Remove the flip-top cap of the appropriate Thyroid 2 - Generator Eluant Vials, 135 mL, Sterile, 881-895 Non-Pyrogenic evacuated vial; disinfect the stopper, allowing (without 46.0 460 230.0 23.0 the stopper to dry before use. Place the 1 - TechneStat™ Vial, 5mL containing perchlorate) evacuated vial into the elution shield utilizing 0.5 mL of 1.5 mg/mL methylparaben and the spacer if required. Thyroid 0.2 mg/mL propylparaben (with 9.7 0.97 48.5 4.85 1- Package Insert 2. Remove the shielded TechneStat'M vial by perchlorate) carefully lifting the TechneStat™ vial shield The sterile, non-pyrogenic solution used to elute from the elution needle. Position the shielded Large Bowel the generator column contains 0.9% sodium evacuated vial by carefUlly lowering the elution (with 19.0 1.90 955 9.55 chloride. The eluant does not contain an shield into the elution station. Piercing the perchlorate) antimicrobial agent. septum of the evacuated vial with the elution needle will begin the elution process. Testes 1.0 0.10 5.1 0.51 EVACUATED COLLECTING VIALS. Collectin9 vials are available on request in 10 and 20 milliliter 3. Wait until the evacuated vial has completely 1Kocher, David C., "Radioactive Decay Tables", Ovaries 22 0.22 11.0 1.10 sizes. filled itself. Depending on the size of the evacuated vial, this may take a few minutes. DOEITIC-11026, 138 (1981). Total Body 1.5 0.15 7.6 0.76 Storage: Never interrupt the elution by lifting the Store generator and Sodium Pertechnetate Tc elution shield! NOTE: Do not use generator 2Modified from: Summary of Current Radiation 99m solution at controlled room temperature eluate if its appearance is discolored. Dose Estimates to Normal Humans from Tc 99m 20-25°C (68-77°F) [See USP Controlled Room 4. Carefully remove the elution shield and replace as Sodium Pertechnetate. MIRD Dose Estimate Temperature]. with the shielded TechneStat™ vial (see Step Report NO.8. J. Nucl. Med., 17 (1):74-7.1976. Expiration Date: 6 of the PREPARATION section). 3Conway, J.J., et aI., Direct and indirect The generator should not be used after the 5. Determine the technetium Tc 99m concentra­ expiration date stated on the label. tion and molybdenum Mo 99 content for radionuclide cystography. J. Urol. 113:689-693, May 1975.