Calibration & Reference Sources (35.65)

Every nuclear medicine department depends on a small set of sealed sources it never injects into a patient. The cobalt-57 and cesium-137 sources that keep the dose calibrator honest, the barium-133 and cobalt-60 accuracy references, the cobalt-57 sheet source that floods the gamma camera, and the germanium-68 source that gives PET systems a 511 keV reference are the quiet backbone of quantitative nuclear medicine. The regulation that lets a medical licensee possess and use them is 10 CFR 35.65, and 10 CFR 35.67 governs how they are leak tested and inventoried.¹²

This guide explains what 35.65 authorizes, the 30 millicurie activity limit and its conditions, the common radionuclides and what each is used for, how leak testing and inventory work under 35.67, and the radiation safety and quality-control practices that keep a reference-source program defensible during inspection.¹²⁷

Introduction

Reference sources matter because they are how a department proves its instruments are telling the truth. A dose calibrator assay of a patient's administered activity is only as trustworthy as the calibrator's constancy, accuracy, linearity, and geometry checks — and those checks are performed with sealed reference sources of precisely known activity. A gamma camera's uniformity depends on a flood source. A PET scanner's quantitative calibration can be traced to a known 511 keV reference. None of these sources is ever administered; their entire job is metrology.⁷

Because they are byproduct material, possessing them requires authorization. Rather than force every clinic to seek a separate license amendment for each small check source, the NRC built the authorization directly into the medical-use rule: 10 CFR 35.65 lets a licensee possess and use calibration, transmission, and reference sources within defined limits. The companion rule, 10 CFR 35.67, sets the leak-test and inventory obligations that apply to sealed sources generally.¹²

This article treats the reference-source program as a radiation safety and quality-control system. For related material, see our guides to sealed source leak testing, the survey meter calibration program, and dose calibrator quality control.

Topic Explanation

What 10 CFR 35.65 authorizes

Section 35.65 authorizes a medical-use licensee to possess and use sealed sources for calibration, transmission, and reference purposes without a separate specific authorization, subject to the rule's conditions. In practice, this is the regulatory basis for the small sealed sources found in every nuclear medicine hot lab and camera room.¹

The rule permits:¹

• Sealed sources not exceeding 1.11 GBq (30 mCi) each, manufactured and distributed by a person licensed under 10 CFR 32.74 (or equivalent Agreement State regulations).
• Sealed sources not exceeding 1.11 GBq (30 mCi) each that are redistributed by a licensee authorized to redistribute them, provided they remain in the manufacturer's original packaging and shielding with the approved instructions.
• Any byproduct material with a half-life no longer than 120 days in non-sealed form, and any byproduct material with a half-life no longer than 120 days as a calibration or reference source, within specified total-activity conditions.

Two conditions are worth emphasizing. First, sources possessed under 35.65 may not be combined or aggregated to create an activity greater than the maximum authorized for any single source. Second, they may not be used for medical use on patients except as otherwise provided in Part 35 — their role is metrology, not therapy or diagnosis in the patient.¹

Key terms

• Calibration source — a sealed source of known activity used to calibrate or check an instrument such as a dose calibrator.
• Reference source — a long-lived sealed source used as a stable standard for constancy and accuracy checks.
• Transmission source — a source (historically Cs-137 or Ge-68) used to acquire transmission data for attenuation correction or to provide a known reference in PET/SPECT systems.
• Flood source — a planar (sheet) source, commonly Co-57, used to measure gamma-camera uniformity.
• Sealed source — byproduct material encased so the material cannot be released under normal use, which is what allows possession without handling the raw radionuclide.

Why the 30 mCi / 120-day structure exists

The limits in 35.65 are deliberately modest. A 1.11 GBq (30 mCi) ceiling on sealed sources keeps the external hazard low enough for routine hot-lab handling behind standard shielding, and the restriction to sources manufactured under 10 CFR 32.74 ensures they come with a Sealed Source and Device (SS&D) registration that has been evaluated for integrity and safe use. The short-half-life provisions accommodate calibration uses of the same radionuclides a department already handles clinically.¹⁵

Key Technical Principles

Common calibration and reference sources

Half-lives are from standard nuclear decay data compilations.⁸⁹ All of these fall comfortably under the 1.11 GBq (30 mCi) ceiling for 35.65 authorization. Their long half-lives are the point: a reference whose activity barely changes over months is a stable metrological standard, and the change it does undergo is handled by a simple decay correction.

Decay correction: the one calculation you always do

A reference source's activity is known precisely only on its assay (calibration) date. On any later date, the expected activity must be decay-corrected before it can be compared against an instrument reading. For an initial activity $A_0$, the activity after elapsed time $t$ is:

Worked example — a Co-57 dose-calibrator reference source. Suppose a Co-57 source was assayed at $A_0=7.4$ MBq (200 µCi). Its half-life is 271.74 days, so:

One year later ($t=365$ d) the expected activity is:

So a constancy check one year after assay should read about 2.92 MBq (79 µCi), not 7.4 MBq. A reading that disagrees with the decay-corrected expected value beyond the acceptance tolerance (commonly within 10% for dose-calibrator constancy) points to an instrument problem, not a decayed source.⁷ This is why the assay date and $A_0$ must be recorded and retained for every reference source.

How the sources feed instrument QC

Reference sources authorized under 35.65 are the inputs to the instrument-QC requirements elsewhere in Part 35 and in NRC guidance:³⁴⁷

• Dose-calibrator constancy — measure a long-lived reference source (Co-57 or Cs-137) on each day of use and compare against the decay-corrected expected activity.
• Dose-calibrator accuracy — assay at least two reference sources spanning the energy range (for example Co-57 and Cs-137, or Ba-133/Co-60) at installation and annually.
• Dose-calibrator linearity — verify the response is linear across the clinical activity range (often using a decaying Tc-99m source over time, or shields).
• Survey-instrument calibration — calibrate survey meters before first use, annually, and after repair, traceable to a known source.
• Gamma-camera uniformity — acquire a flood using a Co-57 sheet source (extrinsic) or a point source (intrinsic).
• PET reference — use a Ge-68 or Na-22 source as a 511 keV reference for calibrator and scanner checks.

The dose-calibrator QC schedule (constancy each day of use, accuracy at installation and annually, linearity quarterly, geometry at installation) is described in NRC licensing guidance such as NUREG-1556 Volume 9 and is the standard of practice.⁷

Clinical Impact

A reference-source program is invisible until it fails, and then it is a patient-safety problem. If the dose calibrator drifts and the constancy source has not caught it, every administered-activity measurement made on that instrument is wrong — which can mean a diagnostic study with the wrong count statistics or, more seriously, a therapy dosage outside the prescribed range. The reference sources are the only independent check standing between an instrument fault and a mis-administration.⁷

The leak-test and inventory requirements have a parallel safety rationale. A sealed source that has lost integrity can contaminate the hot lab, staff, and surfaces, and an unaccounted source is a security and regulatory problem. Because reference sources are long-lived and physically small, they are easy to forget — which is exactly why 35.67 mandates periodic leak testing and a semi-annual physical inventory.²

Practical Optimization Tips

Build the program around records

• Keep the SS&D registration certificate, assay date, and initial activity for every source.¹⁵
• Maintain a source log with location, acquisition, leak-test, and inventory history.
• Record decay-corrected expected activities so daily constancy checks compare against the right number.⁷

Leak test and inventory on schedule

• Leak test applicable sealed sources at intervals not exceeding 6 months, with a method capable of detecting 185 Bq (0.005 µCi) of removable contamination.²
• If a test detects 185 Bq (0.005 µCi) or more of removable contamination, immediately withdraw the source from use, store/dispose/repair it, and file the required report.²
• Conduct the semi-annual physical inventory of all sealed sources and document it.²

Handle and store sensibly

• Store reference sources in labeled, shielded locations consistent with ALARA; their modest activity does not excuse casual storage.⁶
• Dispose of decayed or leaking sources through authorized pathways — do not let obsolete sources accumulate in a drawer, which is a common inspection finding.
• Confirm that any transfer or disposal is to an authorized recipient and is recorded.¹⁶

Common pitfalls

1. Comparing a daily constancy reading against the original assay activity instead of the decay-corrected value.
2. Letting a long-lived source slip past its 6-month leak-test date.
3. Missing a source during the semi-annual inventory because the log is incomplete.
4. Aggregating multiple sources beyond the single-source activity limit.
5. Keeping decayed or retired sources on site without a disposal record.

Regulatory Considerations

Reference-source possession sits squarely inside the NRC (or Agreement State) medical-use framework, and the obligations are specific. The governing provisions are:

• 10 CFR 35.65 — authorization to possess and use calibration, transmission, and reference sources, including the 1.11 GBq (30 mCi) per-source limit, the SS&D-manufacturing condition, the no-aggregation rule, and the prohibition on patient medical use.¹
• 10 CFR 35.67 — leak-test (6-month, 185 Bq detection) and semi-annual physical-inventory requirements for sealed sources, and the actions required on a positive leak test.²
• 10 CFR 35.60 and 35.61 — possession, use, and calibration of instruments used to measure activity (the dose calibrator) and calibration of survey instruments, which the reference sources support.³⁴
• 10 CFR Part 20 — the underlying radiation protection standards, including storage, security of licensed material, surveys, and dose limits that apply to source handling and storage.⁶
• 10 CFR 32.74 — the manufacturing/distribution rule that produces the SS&D-registered sources 35.65 relies on.⁵
• NUREG-1556 Volume 9, Revision 3 — the NRC's program-specific licensing guidance for medical use, which describes the expected instrument-QC practices and documentation.⁷

Jurisdiction depends on the state. DRPS serves facilities across Florida, Maryland, Virginia, Washington DC, California, Nevada, Pennsylvania, New York, New Jersey, and Delaware. Of these, Florida, Maryland, Virginia, California, Nevada, Pennsylvania, New York, and New Jersey are NRC Agreement States that administer their own equivalent radiation-control rules, while Washington DC and Delaware are regulated directly by the NRC for radioactive material. A facility should confirm with the authority having jurisdiction which version of these requirements applies to its license.

Frequently Asked Questions (FAQs)

What does 10 CFR 35.65 authorize?

Section 35.65 authorizes a medical-use licensee to possess and use sealed sources for calibration, transmission, and reference purposes without a separate specific authorization, provided the sources meet the rule's conditions. These are the non-therapeutic sources used to check the dose calibrator, calibrate survey instruments, flood the gamma camera, and serve as PET transmission or reference standards.¹

What is the activity limit for a sealed source under 35.65?

A licensee may possess sealed sources not exceeding 1.11 GBq (30 mCi) each when manufactured and distributed by a person licensed under 10 CFR 32.74 or equivalent Agreement State regulations. The sources may not be aggregated beyond that single-source limit and may not be used for patient medical use.¹

Do calibration and reference sources need to be leak tested?

Yes. Under 10 CFR 35.67, applicable sealed sources generally must be leak tested at intervals not exceeding 6 months, with the test able to detect 185 Bq (0.005 µCi) of removable contamination, and the licensee must perform a semi-annual physical inventory.²

What happens if a leak test is positive?

If a leak test detects 185 Bq (0.005 µCi) or more of removable contamination, the licensee must immediately withdraw the source from use, store/dispose/repair it, and file the required report.²

Which radionuclides are common calibration and reference sources?

Cobalt-57 and cesium-137 are the workhorse dose-calibrator check sources; barium-133 and cobalt-60 are accuracy references; germanium-68 (with gallium-68) provides a 511 keV PET reference; and cobalt-57 sheet sources flood the gamma camera. Their long half-lives make them stable references needing only decay correction.⁸⁹

Can a reference source be used to measure a patient dosage?

No. Sources possessed under 35.65 are for calibration, transmission, and reference use only. They verify that instruments such as the dose calibrator read correctly so that patient dosages measured on those instruments are accurate, but the reference sources themselves are never administered.¹

Key Takeaways

• 10 CFR 35.65 authorizes possession and use of calibration, transmission, and reference sources within defined limits — the regulatory basis for every hot-lab check source.¹
• The per-source limit is 1.11 GBq (30 mCi) for SS&D-manufactured sealed sources; sources may not be aggregated beyond that or used on patients.¹
• 10 CFR 35.67 requires 6-month leak testing (185 Bq detection) and a semi-annual physical inventory, with immediate withdrawal on a positive leak test.²
• Common sources — Co-57, Cs-137, Ba-133, Co-60, Ge-68, Na-22 — are long-lived and need only decay correction, performed with $A(t)=A_0{e}^{-\lambda t}$.⁸⁹
• Reference sources are the independent check that keeps dose-calibrator, survey-meter, and camera QC honest, protecting patients from instrument drift.⁷
• Keep SS&D certificates, assay data, decay-corrected expected activities, leak-test records, and inventory logs for inspection.¹²⁵

How DRPS Can Help

Diagnostic Radiation Physics Services helps nuclear medicine and PET facilities build defensible reference-source and instrument-QC programs: dose-calibrator and survey-meter QC design, leak-test and inventory procedures, source-record systems, and radioactive material license support aligned with NRC and Agreement State requirements — all supported by board-certified medical physicists. See our radioactive material license support, radiation safety officer consulting, and PET/CT and nuclear medicine physics services.

DRPS serves facilities across Florida, Maryland, Virginia, Washington DC, California, Nevada, Pennsylvania, New York, New Jersey, and Delaware.

Conclusion

Calibration, transmission, and reference sources are small, long-lived, and easy to take for granted — and they are the metrological foundation of quantitative nuclear medicine. 10 CFR 35.65 authorizes their possession within sensible limits, 10 CFR 35.67 keeps them safe and accounted for, and the department's own records and decay corrections keep them useful. A facility that treats its reference-source program as a real quality-control system, not a drawer of forgotten sources, protects both its patients and its license.¹²⁷

Related Resources

• Sealed source leak testing
• Survey meter calibration program
• Dose calibrator quality control
• NRC Part 35 recordkeeping requirements
• Nationally tracked sources
• Radioactive material license support
• Radiation Safety Officer consulting

References

1. U.S. Nuclear Regulatory Commission. 10 CFR 35.65: Authorization for calibration, transmission, and reference sources. nrc.gov
2. U.S. Nuclear Regulatory Commission. 10 CFR 35.67: Requirements for possession of sealed sources and brachytherapy sources. nrc.gov
3. U.S. Nuclear Regulatory Commission. 10 CFR 35.60: Possession, use, and calibration of instruments used to measure the activity of unsealed byproduct material. nrc.gov
4. U.S. Nuclear Regulatory Commission. 10 CFR 35.61: Calibration of survey instruments. nrc.gov
5. U.S. Nuclear Regulatory Commission. 10 CFR 32.74: Manufacture and distribution of sealed sources and devices containing byproduct material. nrc.gov
6. U.S. Nuclear Regulatory Commission. 10 CFR Part 20: Standards for Protection Against Radiation. nrc.gov
7. U.S. Nuclear Regulatory Commission. NUREG-1556, Volume 9, Revision 3: Consolidated Guidance About Materials Licenses — Program-Specific Guidance About Medical Use Licenses. 2019. nrc.gov
8. National Nuclear Data Center, Brookhaven National Laboratory. NuDat / Chart of Nuclides: decay data and half-lives. nndc.bnl.gov
9. International Atomic Energy Agency. Quality Assurance for SPECT Systems; and Nuclear Medicine Resources Manual (instrument quality-control references). Vienna: IAEA. iaea.org