Information Notice No. 94-70: Issues Associated with Use of Strontium-89 and other Beta Emitting Radiopharmaceuticals

                          UNITED STATES
                  NUCLEAR REGULATORY COMMISSION
        OFFICE OF NUCLEAR MATERIAL SAFETY AND SAFEGUARDS
                     WASHINGTON, D.C.  20555

                       September 29, 1994


NRC INFORMATION NOTICE 94-70:  ISSUES ASSOCIATED WITH USE OF 
                               STRONTIUM-89 AND OTHER BETA 
                               EMITTING RADIOPHARMACEUTICALS


Addressees

All U.S. Nuclear Regulatory Commission Medical Licensees.

Purpose

The U.S. Nuclear Regulatory Commission is issuing this information notice to
alert its licensees of the following:

     A.   special considerations for assaying pure beta emitting
          radiopharmaceuticals;

     B.   safety considerations for managing patients who have been treated
          with therapeutic dosages of beta emitting radiopharmaceuticals;
          and

     C.   physician training and experience requirements for the therapeutic
          use of radiopharmaceuticals other than I-131 (i.e., strontium-89,
          rhenium-186, samarium-153).

It is expected that recipients will review this information for applicability
to their facilities and consider actions, as appropriate.  However,
suggestions contained in this information notice do not represent new NRC
requirements; therefore, no specific actions or written response is required.

Description of Circumstances

The use of therapeutic quantities of pure beta emitting radioisotopes may pose
special technical difficulties.  These difficulties include assaying of the
radiopharmaceutical dosages and determining the isotope burden of the patient.
Furthermore, opening of the body cavity or exposure to body fluids encountered
in surgery, autopsy, embalming, or cremation may require special precautions
to limit the possible spread of contamination from the radioisotope present in
the patient.  

Strontium-89 (Sr-89) Metastron has an approved New Drug Application (NDA) from 
the Food and Drug Administration (FDA) for use in therapeutic amounts to
reduce bone pain from metastatic bone lesions.  Other beta emitting
radionuclides such as rhenium-186 (Re-186) and samarium-153 (Sm-153) are
currently under review by the FDA for similar approval.  Section 35.300 of


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10 CFR Part 35 authorizes the therapeutic use of Sr-89 Metastron since an NDA
has been approved by the FDA.  

However, the physician training and experience requirements for the use of
Sr-89 or other pure beta emitting radionuclides are not explicitly addressed
in 10 CFR Part 35.  Therefore, this document explains the training and
experience criteria for the therapeutic use of radiopharmaceuticals, other
than I-131.  

Discussion

Assaying Dosages:

Subpart C of 10 CFR Part 35 does not require the use of a dose calibrator to
measure patient dosages of radiopharmaceuticals containing pure beta emitters.
However, it is our understanding that the manufacturer of Sr-89 Metastron has
participated in intercomparisons with the National Institutes of Standards and
Technology (NIST) in the calibration of its beta measurement instruments. 
Therefore, until appropriate measuring instruments and standards are developed
and available, reliance on the manufacturer's stated activity of the unit
dosage may be the most accurate means, and an acceptable method, of
determining the activity of the patient dosage.  

A licensee may use a dose calibrator to accurately measure the patient dosage
containing pure beta emitters; however, there are inherent technical
difficulties to overcome.  These difficulties include, but are not limited to,
dependence upon geometry, lack of an industry standard for the materials used
in the manufacture of both vials and syringes, and a lack of a suitable Sr-89
calibration standard from NIST.  For example, if there is a need to administer
an activity different from the unit dosage supplied by the manufacturer, the
licensee should perform either a volumetric adjustment based on the
manufacturer's stated specific activity, or use the appropriate setting on a
dose calibrator specifically designed and calibrated to measure beta activity. 
If the latter method is used, you should assay patient dosages in the same
type of vial and geometry as used to determine the correct dose calibrator
settings.  The use of different vials or syringes may result in measurement
errors due to the variation of bremsstrahlung created by interaction between
beta rays and the differing dosage containers.  Licensees are reminded that
beta emitters should be shielded using a low-atomic-numbered material to
minimize the production of bremsstrahlung, followed by a high-atomic-numbered
material thick enough to attenuate the bremsstrahlung intensity.   

NRC recently became aware of a case where a licensee inadvertently
administered a therapeutic dose of Sr-89 to a patient when a diagnostic dose
of a different radiopharmaceutical was intended.  Licensees may want to
develop a method for distinguishing between therapy and diagnostic doses, such
as physical separation or using a different colored label.  

If the procedures in your Quality Management Program (QMP) state that you will
measure radiopharmaceuticals for therapy in a dose calibrator, you should
either continue to measure the dosage in the dose calibrator after determining
the appropriate dose calibrator setting or modify the QMP to state that you .                                                  IN 94-70
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will rely on the manufacturer's calibration for unit dosages.  Licensees are
reminded that modifications to the QMP must be furnished to the appropriate
NRC Regional Office within 30 days after the modification has been made
(.35.32(e)).  

In addition, the proposed radiopharmacy rule published in the Federal
Register, June 17, 1993, would require medical use licensees to measure
dosages of alpha- and beta-emitting radionuclides, except for unit dosages
obtained from the manufacturer or commercial nuclear pharmacy.  Also, the
proposed rule would allow a licensee to use a combination of measurements and
calculations to determine the dosage of alpha- or beta-emitting radionuclides. 
It is anticipated that the final rule, which is scheduled to be approved by
the Commission prior to issuance, will be published by early 1995.  

Managing Patients:

Due to the long half-life of some alpha- or beta-emitting radionuclides,
contamination of hospital or funeral home personnel and facilities, in the
event of surgery or death following administration of these
radiopharmaceuticals, is possible.  Licensees administering
radiopharmaceuticals containing Sr-89, or other long lived isotopes, may wish
to review NCRP Report No. 37, Precautions in the Management of Patients Who
Have Received Therapeutic Amounts of Radionuclides, for guidance in managing
these patients.  Although the report does not specifically address Sr-89, it
does provide a guide for persons concerned with care of patients who have
received therapeutic dosages of radionuclides.  Copies of this publication can
be obtained by writing:
 
     National Council on Radiation Protection and Measurements
     7910 Woodmont Avenue
     Bethesda, MD 20814

or, by phoning the NCRP at (301) 657-2652.  Currently, the price is $20.00
plus $3.00 postage.

The main source of exposure to workers handling deceased patients who have
been administered Sr-89 (half-life of 50.5 days) is contamination from contact
with body fluids.  Using extremely conservative assumptions, an estimated skin
dose to workers handling deceased patients was calculated by NRC staff.  The
calculations were based on the typical administered dosage of 4.05 mCi
(150 MBq).  Assuming that all of the activity was in the blood and the patient
died immediately, the skin dose to a worker not wearing gloves was estimated
to be 447 mrads (4.47 x 10-3 Gy) per hour.  Assuming the worker was
contaminated with body fluids and worked for 4 hours with the patient, the
skin dose would be about 1.8 rad (0.18 Gy).  If the worker wears gloves, the
skin dose is reduced to 180 mrads (1.8 x 10-3 Gy) per hour, which gives a skin
dose of 720 mrads (7.2 Gy) when handling a patient for 4 hours.  These skin
doses are within regulatory limits; however, all necessary precautions should
be taken to minimize the dose as much as possible.  In fact, most patients do
not die immediately after receiving Sr-89, and the Sr-89 is rapidly taken up
in the extracellular fluid and intracellularly, primarily in the skeleton with
less than 1 percent of the dosage present in the blood at 140 hours (about 6 .                                                  IN 94-70
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days).  Therefore, any skin doses to a worker should actually be much lower
than the ones estimated previously.  Licensees should use typical precautions,
e.g. use of gloves and protective clothing, in preventing contamination when
using Sr-89 and other beta emitting radioisotopes for therapy.  Workers should
wash their hands and change into clean gloves and laboratory coats/gowns if
the protective clothing becomes contaminated.

The National Radiological Protection Board in the United Kingdom has performed
a radiological assessment to estimate the impact of cremating corpses of
people who have received treatment with Sr-89.  The calculations were based
on an assumption that the entire dose of 4.05 mCi (150 MBq) was present in the
ash.  The maximum dose to a crematorium worker would be about 0.01 mrem
(0.1 �Sv)  (effective) from inhalation of ash, and about 0.02 mrem (0.2 �Sv)
(effective) from ingestion of ash.  Again, these estimates were calculated
using conservative assumptions.  Normal precautions should be taken in
handling the ash as with any other cremation.  Workers typically wear
protective clothing including barrier face masks or respirators when handling
ash.  

Training and Experience:

If a physician is currently authorized for the therapeutic use of
radiopharmaceuticals, (10 CFR 35.300) and requests authorization for
therapeutic use of radiopharmaceuticals other than I-131 (i.e., P-32 or Sr-
89), no additional authorization by license amendment from NRC is required. 
If a physician is NOT currently so authorized by NRC, the training and
experience requirements described in 35.930 would apply, i.e., board
certification by the American Board of Nuclear Medicine or the American Board
of Radiology in radiology or therapeutic radiology; or 80 hours didactic
training and supervised clinical experience with 3 case studies involving the
radiopharmaceutical for which authorization is requested.  
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This information notice requires no specific action or written response.  If
you have questions about the information in this notice, please contact the
technical contact listed below or the appropriate regional office.

                              /S/'D BY CJPAPERIELLO

                              Carl J. Paperiello, Director
                              Division of Industrial and 
                                Medical Nuclear Safety
                              Office of Nuclear Material Safety
                                and Safeguards

Technical contact:  Torre Taylor, NMSS
                   (301) 504-1062     

Attachments:
1.  List of Recently Issued NMSS Information Notices
2.  List of Recently Issued NRC Information Notices