Osteolite

Description for Osteolite

Each vial contains a sterile, non-pyrogenic, lyophilized mixture of
Medronate Disodium -10mg
Stannous Chloride, minimum (SnCI2 • 2H20)-0.6mg
Total Tin, maximum (SnCI2 • 2H20) -1.15mg
Prior to lyophilization, the pH is adjusted to between 7.0-7.5 with HCI and/or NaOH. The contents of the vial are lyophilized and stored under nitrogen.

Administration is by intravenous injection for diagnostic use, after reconstitution with sterile, nonpyrogenic, oxidant-free Sodium Pertechnetate Tc99m Injection.

The precise structure of stannous technetium medronate complex is known at this time (JACS Vol.102, 2476, 1980).

Physical Characteristics

Technetium Tc99m decays by isomeric transition with a physical half-life of 6.02 hours.1 Photons that are useful for imaging studies are listed in Table 1.

Table 1. Principal Radiation Emission Data

Radiation	Mean %/Disintegration	Mean Energy(keV)
Gamma-2	89,07	140.5

1Kocher, David C., 'Radioactive Decay Data Tables', DOE/TIC 11026, 108 (1981).

External Radiation

The specific gamma ray constant for Tc99m is 5.4 microcoulombs/kg-MBq-hr (0.78 R/mCi-hr) at 1cm. The first half value layer is 0.017cm of Pb. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of lead (Pb) is shown In Table 2. To facilitate control of the radiation exposure from MBq (mCi) amounts of this radionuclide, the use of 0.25cm thickness of lead (Pb) will attenuate the radiation emitted by a factor of 1,000.

Table 2. Radiation Attenuation by Lead Shielding

Shield Thickness	Coefficient of Attenuation
lead (Pb) cm	0.5
0.017	10-1
0.08	10-2
0.16	10-3
0.25	10-4
0.33	10-5

To correct for physical decay of this radionuclide, the fractions that remain at selected intervals after the time of calibration are shown in Table 3.

Table 3. Physical Decay Chart; Technetium Tc99m Hall-life 6.02 Hours

Uses for Osteolite

Technetium Tc99m Medronate may be used as a bone Imaging agent to delineate areas of altered osteogenesis.

Dosage for Osteolite

The suggested dose range for I.V. administration to be employed in the average patient (70kg) is:

• 370 to 740 MBq (10-20mCi)

The patient dose should be measured by a suitable radioactivity calibration system immediately prior to patient administration. Radiochemical purity should be checked prior lo patient administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Optimal imaging results are obtained 1-4 hours after administration. The image quality may be adversely affected by obesity, old age, and impaired renal function.

Store at controlled room temperature (20-25°C) before and after reconstitution.

Instructions for Preparation of Technetium Tc 99m Medronate Injection

Preparation of Technetium Tc99m Medronate from Kit for the Preparation of Technetium Tc99m Medronate is done by the following aseptic procedure:

1. Prior to adding the Sodium Pertechnetate Tc99m Injection to the vial, write the estimated activity, date and time of preparation in the space provided on the vial label. Then tear off a radiation symbol and attach it to the neck of the vial.
2. Waterproof gloves should be worn during the preparation procedure. Remove the plastic disc from the vial and swab the top of the vial closure with alcohol to sanitize the surface.
3. Place the reaction vial in a suitable radiation shield with a fitted radiation
4. With a sterile, shielded syringe, aseptically obtain 2-8ml [maximum 7.4 GBq (200mCi)] of a suitable, oxidant-free, sterile, non-pyrogenic Sodium Pertechnetate Tc99m Injection.
5. Aseptically add the Sodium Pertechnetate Tc99m Injection to the
6. Place the radiation shield cap on the vial shield and swirl the contents of the vial for one minute and let stand for 1-2 minutes.
7. Maintain adequate shielding during the life of the product by using the radiation vial shield with the radiation shield cap in place and by using a syringe shield for withdrawing and injecting the
8. Using proper shielding, the vial containing the reconstituted solution should be visually inspected to ensure that it is free of particulate matter prior to Do not use if the solution is cloudy.
9. Assay the product in a suitable dose calibrator, then complete and affix the "radioactive contents" label to the vial shield
10. Aseptically withdraw material for use within six (6) hours. Store reconstituted vial at controlled room temperature (20- 25°C). The vial contains no preservative

Radiation Dosimetry

The estimated absorbed radiation doses2 to organs and tissues of an average patient (70kg) from an intravenous injection of 740 MBq (20mCi) of Technetium Tc99m Medronate are shown in Table 4.

Table 4. Radiation Absorbed Doses

Organ	Radiation mGy/740MBq	Absorbed Dose (rads/20mCi)
Total Body	1.3	(0.13)
Bone Total	7.0	(0.70)
Red Marrow	5,6	(0.56)
Kidneys	8.0	(0.80)
Liver	0.6	(0.06)
Bladder wall
2 hr void	26.0	(2.60)
4.8 hr void	62.0	(6.20)
Ovaries
2 hr void	2.4	(0.24)
4.8 hr void	3.4	(0.34)
Testes
2 hr void	1.6	(0.16)
4.8 hr void	2.2	(0.22)

²Method of Calculation: "S", Absorbed Dose per Unit Cumulated Activity for Selected Radionuclides and Organs, MIRD Pamphlet No. 11 (1975).

HOW SUPPLIED

OSTEOLITE® Kit for use in the preparation of Technetium Tc99m Medronate for Injection is supplied in kits of five (5) or thirty (30) vials, sterile and non-pyrogenic.

Prior to lyophilization the pH is adjusted to between 7.0-7.5 with hydrochloric acid and/or sodium hydroxide solution. The contents of the vial are lyophilized and stored under nitrogen. Store at controlled room temperature (20 -25°C) before and after reconstitution. Technetium Tc99m Medronate contains no preservatives. Included in each live (5) vial kit is one (1) package insert and twelve (12) radiation labels. Included in each thirty (30) vial kit is one (1) package insert and seventy-two (72) radiation labels.

This reagent kit for the preparation of a radiopharmaceutical is approved for use by persons licensed pursuant to Section 120.533, Code of Massachusetts Regulation 105, or under equivalent license of the U.S. Nuclear Regulatory Commission or an Agreement State.

Marketed by CIS·US, Inc. 10 DeAngelo Drive Bedford, MA, USA 01730

Warnings for Osteolite

Included as part of the PRECAUTIONS section.

Precautions for Osteolite

This class of compounds is known to complex cations such as calcium. Particular caution should be used with patients who have, or who may be predisposed to, hypocalcemia (i.e. alkalosis).

Preliminary reports indicate impairment of brain scans using Sodium Pertechnetate Tc99m Injection which have been preceded by a bone scan using an agent containing stannous ions. The impairment may result in false-positive or false-negative brain scans It is recommended, where feasible, that brain scans precede bone imaging procedures.

Alternatively, a brain imaging agent such as Technetium Tc99m Pentetate may be used.

The biodistribution of technetium Tc 99m medronate may be altered in the presence of high levels of certain cations (iron, calcium, and aluminum). This may result in reduced uptake of radionuclide in the skeleton and increased extraosseal uptake, which may potentially degrade imaging quality. High levels of these cations may be caused by concomitant medications or medical conditions (e.g., iron overload, hypercalcemia, etc.). Most cases were observed after iron infusion. (See PRECAUTIONS, Drug Interactions.)

To minimize the radiation dose to the bladder, the patient should be encouraged to increase his fluid intake and to void as often as possible after the Injection of Technetium Tc99m Medronate. and for 4 to 6 hours alter the imaging procedure.

The preparation contains no bacteriostatic preservatives. Technetium Tc99m Medronate should be used within six hours of preparation.

General

The contents of the vial are intended only for use in the preparation of Technetium Tc99m Medronate and are NOT to be administered directly to the patient.

Radioactive drugs must be handled with care and appropriate safety measures should be used to minimize radiation exposure to clinical personnel. Also, care should be taken to minimize radiation exposure to the patients consistent with proper patient management.

The components of the kit are sterile and non-pyrogenic. It is essential to follow directions carefully and to adhere to strict aseptic procedures during preparation.

Technetium Tc99m labeling reactions involved depend on maintaining the stannous ion in the reduced state. Hence, Sodium Pertechnetate Tc99m Injection containing oxidants should not be used.

Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term animal studies have been performed to evaluate carcinogenic potential or whether Technetium Tc99m Medronate affects fertility in males or females.

Clinical Pharmacology for Osteolite

During the initial twenty-four hours following intravenous injection of Technetium Tc99m Medronate, about 50% of the dose is retained in the skeleton, and about 50% is renally excreted; less than 2% of the injected dose remains in the vascular system. Blood levels fall to 3-5% of the injected dose by three hours post-injection.

Upon intravenous injection, osseous uptake of Technetium Tc99m Medronate appears to be related to bone metabolic activity and to skeletal blood flow. Technetium Tc99m Medronate exhibits a specific affinity for areas of altered osteogenesis.

Patient Information for Osteolite

No information provided.