RUBRATOPE^®-57
Cyanocobalamin Co 57 Capsules USP
DIAGNOSTIC CAPSULES

DESCRIPTION Rubratrope-57 diagnostic capsules for oral administration provide radioactive cyanocobalamin in which a portion of the molecules contain Co 57 in the molecular structure vitamin B₁₂-⁵⁷Co. The chemical structure of cyanocobalamin is given below:

Each Rubratope-57 capsule contains approximately 18.5 to 37 kBq (0.5 to 1.0 microcurie) of cyanocobalamin Co 57; the cyanocobalamin span of each capsule will vary with the specific activity of the cyanocobalamin Co 57 used. Complete assay data are provided on the vial label.

Cobalt 57 decays by electron capture with a physical half-life of 270.9 days.Kocher, David C., “Radioactive Decay Data Tables”, DOE/TIC-11026, (1981) p.77. Photons that are useful for detection and imaging studies are uled in Table 1.

The specific gamma ray constant for Co 57 is 0.96 R/hour-millicurie at 1 cm. The first half-value thickness of Pb (lead) for Co 57 is 0.006 cm. To facilitate control of the radiation exposure, a range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 2. For example, the use of 1.6 cm of Pb will decrease the external radiation exposure by a factor of about 1,000.

After oral administration, cyanocobalamin is normally bound by intrinsic factor and absorbed by the distal ileum. It is then bound to plasma proteins, stored in the liver, and slowly released when needed to carry out normal cellular metabolic functions. Absorbed cyanocobalamin is ultimately excreted in the urine; any cyanocobalamin not bound by intrinsic factor is excreted in the stool.

Rubratope-57 (Cyanocobalamin Co 57 Capsules) is intended for the diagnosis of pernicious anemia and as a diagnostic adjunct in other defects of intestinal vitamin B₁₂ absorption.

None known.

None.

In the use of any radioactive material, care should be taken to insure minimum radiation exposure to the patient and occupational workers consistent with proper patient management.

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.

Because a large parenteral dose of vitamin B₁₂ may temporarily affect subsequent intestinal absorption and excretion of the vitamin, tests employing radioactive vitamin B₁₂ should not be performed for at least 24 hours after either a flushing dose for the Schilling test or a therapeutic injection (1000 micrograms) of vitamin B₁₂.

Most antibiotics, methotrexate, pyrimethamine, colchicine, para-aminosalicylic acid, or excessive alcohol intake for longer than two weeks may result in malabsorption of vitamin B₁₂.

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

Since vitamin B₁₂-⁵⁷Co is excreted in human milk during lactation, formula feedings should be substituted for breast feedings.

Safety and effectiveness in children have not been established.

No adverse reactions specifically attributable to Cyanocobalamin Co 57 Capsules have been reported.

The following adverse reactions have been reported with nonradioactive cyanocobalamin: mild transient diarrhea, polycythemia vera, peripheral vascular thrombosis, itching, transitory exanthema, feeling of swelling of the entire body, congestive heart failure and pulmonary edema, anaphylactic shock, and death.

The suggested oral dose range for the average patient (70 kg) when performing a Schilling urinary excretion test is between 18.5 to 37 kBq (0.5 to 1 microcurie) of cyanocobalamin Co 57.

The patient dose in each Cyanocobalamin Co 57 Capsule should be measured by a suitable radioacttivity calibration system immediately prior to administration.

The estimated absorbed radiation doses to an average patient (70 kg) from an oral dose of 37 kBq (1 microcurie) of vitamin B₁₂-⁵⁷ Co are shown in Table 4.

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

*The administration of a flushing dose of nonradioactive vitamin B₁₂ will decrease the dose to the liver, gonads, and whole-body from Co 57 by about 30 percent.

Rubratope-57 (Cyanocobalamin Co 57 Capsules) is available in bottles of 5 and 10 capsules. Each two-piece blue/red capsule contains approximately 18.5 to 37 kBq (0.5 to 1 microcurie) at the time of calibration. Complete assay data are provided on the container.

Cobatope-57 (Cobaltous Chloride Co 57 Reference Standard Solution), supplied in 10 mL vials, is manufactured in companion lots to the diagnostic capsules. Cobatope-57 is intended for laboratory use only as a standard of comparison to the diagnostic capsules. Each mL of aqueous solution provides activity equivalent to 2 percent of the total radioactivity in each capsule bearing the same lot number as the reference standard solution. No decay corrections are necessary when the capsules are used with a companion vial of Cobatope-57 (Cobaltous Chloride Co 57 Reference Standard Solution).

Rubratope-57 Diagnostic Kit (Cyanocobalamin Co 57 Diagnostic Kit) provides material for primary and initial retesting (Schilling test) for two patients.

Rubratope-57 (Cyanocobalamin Co 57) capsules should be stored at 20-25°C (68-77°F) [See USP].

• McIntyre PA: “Use of Radioisotope Techniques in the Clinical Evaluation of Patients with Megaloblastic Anemia”, Semin in Nucl. Med. 5:1 (1975), 79-94.
• Nickoloff EL: “Alternatives to Vitamin B₁₂ Radioassays: The Schilling Test”, The Ligand Quart 2: (1979), 27-29.

“This package conforms to the conditions and limitations specified in 49 CFR 173.421 for exempted radioactive material, limited quantity, N.O.S. UN 2910”.

Receipt, transfer, handling, possession or use of this product is subject to the radioactive materials regulations and licensing requirements of the U.S. Nuclear Regulatory Commission, Agreements States or Licensing States as appropriate.

Manufactured for
Bracco Diagnostics Inc.
Princeton, NJ 08543
by Amersham plc Little Chalfont England

L/4734/04/04
Revised April 2004