NRC Medical Use of Byproduct Material — Nuclear Medicine and Radiation Therapy Licensing

Technetium-99m coursing through cardiac arteries for a SPECT scan. Iodine-131 ablating a hyperthyroid gland. Iridium-192 seeds placed centimeters from a prostate tumor. Fluorine-18 glucose lighting up a PET scan for cancer staging. These are all regulated uses of byproduct material — radioactive isotopes produced in nuclear reactors or particle accelerators — administered to patients under strict federal licensing requirements. 10 CFR Part 35 establishes the NRC's comprehensive framework for medical use of byproduct material: who may administer it, what training they must have, when a written authorization is required, how dose delivery must be verified, what safety precautions must surround radiation therapy devices, and when accidents must be reported. Every hospital, clinic, or physician group that administers radioactive materials to patients — whether for diagnostic imaging or treatment — must hold a specific NRC or Agreement State license, employ credentialed authorized users and medical physicists, and follow procedures designed to ensure the right patient gets the right radiopharmaceutical at the right dose by the right route.

Current Rule (2026)

What This Rule Does

10 CFR Part 35 — Medical Use of Byproduct Material — covers every aspect of nuclear medicine and radiation therapy practice. "Byproduct material" under the Atomic Energy Act includes any radioactive isotopes produced in nuclear reactors or particle accelerators: the technetium-99m used in bone scans and cardiac imaging, the fluorine-18 in PET scanners, the iodine-131 used to treat thyroid cancer and Graves disease, the yttrium-90 microspheres used to treat liver tumors, and the high-energy sealed sources (iridium-192, cobalt-60, cesium-131) used in external beam radiation therapy, brachytherapy, and gamma stereotactic radiosurgery (the Gamma Knife).

The rule divides medical uses into categories based on radiation hazard:

• Diagnostic uses (no written directive required): unsealed byproduct material used for uptake, dilution, and excretion studies; imaging procedures like SPECT, PET, and thyroid uptake — where doses are small, effects reversible, and the primary concern is ensuring no contamination reaches the patient
• Therapeutic uses (written directive required): higher-risk administrations where a wrong dose could cause radiation injury — iodine-131 therapy, any therapeutic injection of unsealed material, brachytherapy, and external beam therapy

Key Provisions

• § 35.11 — License required: no person may manufacture, possess, prepare, use, or transfer byproduct material for medical use without a specific license from the NRC or an Agreement State. Hospitals, clinics, and solo practitioners all need separate licenses tied to a physical address. Physicians who administer under the supervision of a licensed authorized user don't need their own license, but the supervising authorized user's license must specifically authorize the use.
• § 35.40 — Written directives: a written directive (signed, dated order from an authorized user) is required before administering: (1) iodine-131 sodium iodide in quantities over 30 µCi; (2) any therapeutic dose of unsealed byproduct material; (3) any therapeutic administration of a sealed source. The directive must specify the radiopharmaceutical or source, the dose, and the site of administration. This is nuclear medicine's equivalent of a prescription — the physician's authorization that the specific treatment is appropriate for this patient.
• § 35.41 — Procedures for written directive administrations: for every administration requiring a written directive, the licensee must have written procedures to verify: the patient's or subject's identity before administration; that the administration is performed in accordance with the directive; and that any unintended deviation is identified and corrected. A two-person check (authorized user and nuclear pharmacist/technologist) before administering a therapeutic dose is the standard compliance mechanism.
• § 35.50–35.57 — Authorized personnel training requirements:
  • Radiation Safety Officer (RSO): must be certified by an NRC-recognized specialty board (e.g., American Board of Radiology, American Board of Health Physics), or complete 200 hours of classroom training plus 1 year of full-time experience under a certified RSO
  • Authorized medical physicist: must be certified by a specialty board (e.g., American Board of Radiology in Medical Physics) or hold a master's/doctoral degree plus 3 years of full-time work experience
  • Authorized nuclear pharmacist: must be a licensed pharmacist who is board-certified in nuclear pharmacy or completes 700 hours of classroom and clinical training
  • Authorized user physician: board certification in nuclear medicine or nuclear radiology, or completion of residency training that includes NRC-required hours of work experience in the specific use category (uptake/dilution, imaging, therapy with unsealed material, brachytherapy, etc.)
• § 35.60 — Calibration and check of survey instruments: licensees must calibrate radiation survey instruments at installation and at least every 12 months, and check for proper function before each use.
• § 35.63–35.67 — Radiopharmaceutical dosage calibration and sealed source testing: each radiopharmaceutical dose must be assayed for activity in a dose calibrator before administration; sealed sources must be tested for leakage every 6 months using leak test kits (showing <0.005 µCi removable contamination).
• § 35.75 — Release of patients containing radiopharmaceuticals: a patient administered radioactive material may be released when the dose to any likely maximally exposed individual would not exceed 5 mSv (500 mrem). For iodine-131, this typically means patients treated with high doses are hospitalized in radiation-controlled rooms until their body burden decreases — smaller diagnostic doses can often be discharged with patient instructions on minimizing family exposure.
• § 35.315 — Safety precautions for hospitalized patients: patients treated with therapeutic doses of unsealed byproduct material who cannot be immediately released must be quartered in a private room with private sanitary facilities. Their room must be posted with radiation warning signs; visitors must be limited; nursing staff must receive radiation safety instruction. Medical waste (bedpans, linens, vomitus) must be treated as potentially contaminated.
• § 35.600–35.632 — Remote afterloaders, teletherapy units, and gamma stereotactic radiosurgery: these devices use sealed sources (typically high-dose-rate iridium-192 for afterloaders, cobalt-60 or cesium-137 for teletherapy, cobalt-60 for Gamma Knife) to deliver precise radiation doses. Requirements include: treatment rooms with radiation-controlled access and electronic door interlocks; continuous viewing and two-way communication with the patient during treatment; emergency source retraction procedures; full calibration of each unit before first use and after source replacement; periodic quality assurance measurements; only licensed personnel may maintain or repair the units.
• § 35.3045 — Medical event reporting: a medical event (formerly "misadministration") must be reported to the NRC Operations Center by telephone within 24 hours of discovery. A medical event occurs when a patient receives a dose that deviates from the authorized use by: (a) the total dose differing from the prescribed dose by more than 20%, or (b) the wrong radiopharmaceutical, wrong route, or wrong patient. A written report to NRC follows within 15 days. The authorized user and the patient (or patient's physician) must be notified.
• § 35.3047 — Dose to embryo/fetus or nursing child: if a pregnant patient inadvertently receives a dose to the embryo/fetus exceeding 50 mSv (5 rem) — a particular concern for I-131 therapy of a patient not known to be pregnant — the licensee must report within 24 hours and provide counseling.

How It Affects You

If you've had a nuclear medicine procedure (bone scan, cardiac stress test, PET scan): the technetium or FDG you received was administered under an NRC or Agreement State license. The physician who ordered it may be the authorized user, or may have prescribed it and had a nuclear medicine physician administer it. The dose you received was measured in a dose calibrator before injection, and the facility must maintain records of your dose for 3 years. For diagnostic procedures, radiation doses are similar to a CT scan — medically justified but not zero.

If you've had iodine-131 therapy (for hyperthyroidism or thyroid cancer): you received a written directive — the authorized user's signed order specifying exactly what dose of I-131 to give you. If your dose was large enough to hospitalize you (typically >30 mCi for thyroid cancer ablation), you were in a radiation-controlled room until your body activity decreased below release criteria. After discharge, you received instructions for minimizing radiation to family members — staying at arm's length, using separate bathroom, avoiding children and pregnant women for days to weeks depending on dose.

If you've had radiation therapy (external beam, brachytherapy, or Gamma Knife for brain tumors): the radiation therapy device (linear accelerator, afterloader, or Gamma Knife) was either NRC-licensed as a byproduct material source, or regulated under state radiation control programs if only X-ray-based. The medical physicist and radiation oncologist who planned your treatment, the dosimetrist who calculated your doses, and the radiation therapists who delivered treatment all operated under qualification requirements that trace back to Part 35 or the Agreement State equivalent.

If you work in nuclear medicine or radiation oncology: every procedure you perform requires knowing whether it's under a written directive. Your facility's license determines what uses are authorized — if your license doesn't authorize a particular radiopharmaceutical or device, you can't use it without a license amendment. Training records and authorized user status must be maintained and updated; if you take on a new procedure type (e.g., Zevalin Y-90 therapy when you've only been authorized for diagnostic agents), you need additional training and a license amendment.

Statutory Authority

This rule implements:

• 42 U.S.C. § 2111 (Atomic Energy Act § 81) — Requires an NRC license to transfer, deliver, receive, acquire, possess, or use byproduct material
• 42 U.S.C. §§ 2133–2134 — Authorizes NRC to issue licenses for civilian uses of atomic energy, including medical uses, under conditions that protect public health and safety
• 42 U.S.C. § 5841 — Establishes the NRC as an independent regulatory agency

The Agreement State program (42 U.S.C. § 2021) allows states to assume NRC's regulatory authority over byproduct material — 39 states have Agreement State status as of 2026 and administer their own Part 35 equivalent programs. NRC retains authority over the few remaining non-Agreement States.

Implementing Regulations — Consumer and Industrial Byproduct Licenses

10 CFR Part 32 — Specific Domestic Licenses to Manufacture or Transfer Certain Items Containing Byproduct Material: the NRC's licensing framework for manufacturers who incorporate radioactive byproduct material into finished consumer and industrial products — a distinct tier of regulation from the medical use licenses in Part 35. Part 32 covers the upstream manufacturing stage: the companies that make smoke detectors containing americium-241, the companies that make self-luminous exit signs using tritium gas, industrial gauges, calibration sources, and other products that contain licensed quantities of radioactive material and are ultimately distributed to end users under general licenses (no end-user license required).

The framework works in two steps: the manufacturer holds a Part 32 specific license (covering manufacturing and initial distribution); the end user — the homeowner with a smoke detector, the building with tritium exit signs — is a generally licensed user under 10 CFR § 31.5, which authorizes possession of finished products with no individual NRC license required.

• § 32.14 — Certain items containing byproduct material (manufacture and initial transfer): the core manufacturing license category for consumer products; an applicant must demonstrate: (1) the product design limits radiation dose to members of the public to an acceptable level; (2) the product will not be opened, damaged, or otherwise altered in ordinary use; (3) the product is labeled with radiation hazard warnings and proper disposal instructions; (4) the manufacturer will maintain records of all units distributed; examples include:
  • Ionization smoke detectors containing americium-241 (Am-241): typically ~1 microcurie each; the ionization current between two electrodes is disrupted by smoke particles, triggering the alarm; Am-241 is an alpha emitter — essentially no external radiation hazard under normal use, but inhalation of the source material would be a significant internal dose concern; NRC Part 32 licenses cover manufacturers like BRK Electronics/First Alert; the general license at 10 CFR § 31.5 allows homeowners and businesses to possess them without any individual license
  • Self-luminous exit signs containing tritium (H-3): the radioactive tritium gas in tubes provides a continuous glow without electricity; typically 25 Curies of tritium per sign; tritium is a low-energy beta emitter with minimal external dose potential; disposal is the key regulatory concern — tritium signs must be returned to the manufacturer or disposed of as radioactive waste, not discarded in regular trash; Part 32 manufacturers (Isolite, Safety Sign) must accept returns of their signs for proper disposal
  • Calibration sources and reference standards: radioactive sources used in laboratories and hospitals to calibrate instruments must also come from Part 32-licensed manufacturers; the calibration sources for dose calibrators (used in nuclear medicine to verify radiopharmaceutical doses before patient injection) must meet specified activity tolerances
• § 32.15 — Quality assurance and labeling: Part 32 manufacturers must maintain a quality control program ensuring that each product meets the design specifications; each unit must be labeled with: the radionuclide, activity quantity, date of manufacture, a radiation warning symbol, and disposal instructions; the label must identify the manufacturer and model number to enable regulatory tracking; NRC may inspect manufacturing facilities to verify QC programs and production records
• § 32.16 — Records and reports of transfer: manufacturers must maintain records of every transfer of byproduct material in finished products — by name and address of each transferee, the radionuclide, activity, and date; for nationally tracked sources (high-activity sources above specified thresholds — primarily for industrial radiography and medical teletherapy), the records are reported electronically to the National Source Tracking System (NSTS)
• § 32.201 — Serialization of nationally tracked sources: high-activity sealed sources that qualify as "nationally tracked sources" (defined in Appendix E to 10 CFR Part 20 — primarily Category 1 and 2 sources manufactured for industrial radiography, brachytherapy, teletherapy, and irradiators) must be individually serialized with a unique source identification number assigned by the manufacturer before transfer; the serial number and source data must be registered in the NSTS within 7 days of manufacture; the NSTS is the primary mechanism for tracking high-activity sources throughout the U.S. — enabling NRC and Agreement States to locate sources, detect losses, and respond to orphan source discoveries

The Part 32 licensing framework creates traceability from radioactive material manufacturer to end product: Part 32 licensees report their distributions to NRC, the NSTS tracks individual high-activity sources, and the general license framework (10 CFR Part 31) covers the final end users. When a radioactive source is reported stolen, lost, or found without an owner at a scrap facility, the NSTS and Part 32 distribution records are the primary tools for identification.

10 CFR Part 31 — General Domestic Licenses for Byproduct Material: the end-user tier of the manufacturer-to-consumer licensing framework. Where Part 32 licenses the manufacturer, Part 31 automatically licenses the end user — any person who acquires a finished product listed in Part 31 is a "generally licensed" user by operation of law, with no individual application, fee, or NRC approval required. General licenses exist because the products involved are designed with intrinsic containment (sealed sources, permanent installation, or product construction that prevents release under ordinary use), making individual licensing of millions of end users unnecessary and impractical.

• § 31.5 — General license for consumer products (smoke detectors, self-luminous devices, gauging instruments): any person is generally licensed to possess and use certain consumer and industrial products distributed under a Part 32 manufacturer's license, including: ionization smoke detectors containing ≤1 microcurie of Am-241; self-luminous aircraft instrument dials, markers, and other devices using ≤0.25 microcuries of tritium or promethium-147 per device; static elimination devices containing ≤500 microcuries of polonium-210; and industrial gauging devices (thickness gauges, level gauges, moisture gauges) within specified source activity limits; the general license imposes obligations on the possessor — proper storage and disposal, prohibition on abandonment, and return to the manufacturer or a licensed radioactive waste broker rather than disposal in regular trash; homeowners who discard smoke detectors in ordinary waste are technically violating the general license conditions, though NRC enforcement focuses on industrial and commercial possessors rather than individual consumers

• § 31.7 — Luminous safety devices for aircraft: a distinct general license for aircraft-installed self-luminous safety devices — compasses, attitude indicators, heading indicators, and altitude markers — that use tritium (up to specified activity levels) or promethium-147; aircraft mechanics and operators are generally licensed to possess these devices during installation, maintenance, and removal; aircraft avionics shops that regularly handle these devices must maintain records of transfers and disposals; the tritium in these devices does not create an external radiation hazard (tritium's beta particles cannot penetrate the device enclosure) but proper disposal is required because tritium-contaminated devices sent to landfills create a groundwater contamination pathway as the tritium gas escapes the aging device

• § 31.10 — Strontium-90 in ice detection devices: aircraft wing anti-icing systems and runway ice detection equipment may contain strontium-90 (Sr-90, a pure beta emitter) used as a reference ionization source in precipitation static detection instruments; operators of aircraft equipped with Sr-90 ice detection devices hold a general license; the § 31.10 general license is a legacy provision — modern ice detection systems have largely moved to non-radioactive sensing technologies, but older aircraft still in service may have these components

• § 31.11 — General license for in vitro clinical or laboratory testing: physicians and clinical laboratories are generally licensed to receive, possess, use, and transfer byproduct material for in vitro (outside the patient body) clinical and laboratory testing, including: radioimmune assay (RIA) kits for measuring hormones, drugs, and biological markers; blood cell labeling for kinetic studies (using chromium-51-labeled red cells); receptor binding assays; and flow cytometry applications; this general license enables the commercial distribution of radioactively labeled immunoassay kits to clinical laboratories without requiring each laboratory to hold a specific NRC license; the general license is limited to in vitro applications — any administration to patients (even diagnostic) requires a specific Part 35 medical use license; the kit manufacturer holds the Part 32 license; the clinical laboratory holds the Part 31 general license; the general license carries record-keeping requirements for quantities received and used

• § 31.12 — Radium-226 self-luminous products: a general license for the possession of antique instruments, watches, clock dials, and similar self-luminous products containing radium-226 manufactured before 1978; Ra-226 was the standard self-luminous paint material before tritium and promethium replaced it; owners of pre-1978 radium-dial instruments and antiques are generally licensed possessors; § 31.12 prohibits: opening or dismantling the device; disposing of it as ordinary trash; and transferring it to anyone other than a licensed radium distributor or waste disposal facility; the historical use of Ra-226 in luminous paint has left a significant legacy contamination issue — dial-painting facilities (most notably the Radium Girls facilities in New Jersey and Illinois) generated widespread environmental contamination that became Superfund sites; radium's decay chain produces radon, making Ra-226 sources an indoor air quality concern if damaged

The general license system illustrates a core principle of NRC's tiered licensing approach: the regulatory burden falls on the entity best positioned to control the hazard. The Part 32 manufacturer, who designs the product, selects the source activity, and specifies disposal requirements, holds the specific license and bears the primary regulatory obligations. The end user — who merely possesses the finished product — benefits from the general license, which provides legal authorization without administrative friction while still imposing minimum obligations (proper storage, prohibited disposal in ordinary waste, prohibited modification) commensurate with the limited exposure risk the product presents in normal use.

10 CFR Part 36 — Licenses and Radiation Safety Requirements for Irradiators (NRC, 34 sections across 6 subparts — the licensing and safety standards for large-scale irradiation facilities that use high-activity sealed sources to irradiate objects and substances for commercial, industrial, and research purposes; authority: 42 U.S.C. § 2111, 42 U.S.C. § 5841). Irradiators are categorurized into two types based on their shielding approach:

• Panoramic irradiators: large-scale facilities in which sealed sources (typically cobalt-60 or cesium-137 in rod form, each containing millions of curies of activity) are elevated from a shielded position to expose product passing through the radiation room on a conveyor; radiation shielding is provided by massive concrete walls (typically 6+ feet thick); panoramic irradiators are used for food irradiation (killing E. coli, Salmonella, and Listeria in meat, poultry, and produce), medical device sterilization (implants, surgical instruments, sutures), and radiation processing (crosslinking polymers, curing coatings); major U.S. operators include Sterigenics, Nordion/Sotera Health, and food irradiation facilities in Florida and Hawaii
• Underwater (pool) irradiators: sealed sources are stored submerged in a deep pool of purified water; product is lowered into the pool for irradiation; shielding is provided by the water column depth (typically 14+ feet of water above the sources in their storage position reduces dose at the surface to acceptable levels); pool irradiators are used in research, blood irradiation (preventing transfusion-associated graft-versus-host disease), and small-scale product irradiation; Cs-137 was historically the source material for pool irradiators, but its water solubility (if a capsule leaked, cesium would dissolve and contaminate the pool — a major radiological hazard) drove a policy shift toward cobalt-60 or dry-source designs after several incidents

Subpart B — Specific Licensing Requirements (§§ 36.11–36.19): any person seeking to operate an irradiator must obtain a specific license from NRC (or an Agreement State); § 36.11 — application must include a detailed facility description, proposed operating and emergency procedures, a training plan for operators, and a description of the radiation safety program; § 36.15 — construction prohibition before license: construction of a new irradiator facility cannot commence before submitting both a license application and a safety analysis — this pre-construction review prevents building a facility that cannot meet NRC standards; § 36.21 — sealed sources must have a certificate of registration under 10 CFR § 32.210 (confirming they meet source containment standards) and must be doubly encapsulated (two independent encapsulation barriers) to prevent source material release if the outer capsule is breached

Subpart C — Design and Performance Requirements (§§ 36.21–36.39 — largest subpart):

• § 36.23 — Access control: each entrance to a panoramic irradiator's radiation room must have a door or physical barrier preventing inadvertent entry when sources are exposed; the control system must prevent source exposure if any entrance is not secured; the source can only be moved to the exposed position from the facility's main control panel (no remote or autonomous exposure initiation)
• § 36.25 — Shielding: dose rates in normally occupied areas outside the radiation room may not exceed 0.02 millisievert (2 millirems) per hour when sources are in the exposed position; this limit applies to operator stations and adjacent rooms
• § 36.27 — Fire protection: panoramic irradiator radiation rooms must have heat and smoke detectors with audible alarms; automated source retraction (sources return to shielded position) on fire or loss of power; fire suppression systems may not use water in areas where flooding could threaten source integrity
• § 36.29 — Radiation monitors: irradiators with automatic product conveyor systems must have radiation monitors near the product exit to detect loose or mishandled sources being inadvertently transported out of the radiation room — a critical safeguard against source loss, which has historically been the most serious irradiator accident scenario
• § 36.31 — Emergency source return: all panoramic irradiators must have a system capable of returning sources to their shielded position upon loss of electrical power; sources must never remain exposed after an unplanned shutdown; the emergency source retraction system must operate on backup power

Subpart D — Operation of Irradiators (§§ 36.51–36.69):

• § 36.51 — Training: no one may operate an irradiator without a supervisor present unless they have been formally trained on radiation protection fundamentals, operating procedures, emergency procedures, personnel monitoring, and the specific hazards of that irradiator design
• § 36.55 — Personnel monitoring: all operators working with panoramic irradiators must wear a personnel dosimeter; thermoluminescent dosimeters (TLDs) or optically stimulated luminescent (OSL) dosimeters are exchanged monthly; operators' annual dose must not exceed the occupational limits in 10 CFR Part 20 (50 mSv/year effective dose)
• § 36.59 — Detection of leaking sources: each dry-source-storage sealed source must be tested for leakage at 6-month intervals; a wipe test is performed and analyzed for radioactive contamination; leaking sources must be immediately isolated and NRC notified; leaking cobalt-60 sources at panoramic irradiators have been responsible for the most serious irradiator incidents in U.S. history (the Decatur, Alabama Sterigenics incident 2010; the Hualapai Indian Reservation source orphan incident)
• § 36.65 — Two-person rule: both an irradiator operator and at least one other trained individual must be present whenever an operator enters the radiation room of a panoramic irradiator; the second person must be outside the room, prepared to respond or summon assistance; this "buddy system" requirement prevents a single operator from becoming incapacitated inside the radiation room undetected
• § 36.63 — Pool water purity: underwater irradiators must maintain pool water conductivity below 20 microsiemens/cm (near-deionized quality) to prevent corrosion of source capsules; corroded capsules can release radioactive material into the pool water, creating an uncontrolled contamination event; the Part 63 water quality limit is a fundamental safeguard against pool irradiator source degradation

Safety significance: irradiators contain among the highest activities of radioactive material in the NRC-licensed inventory outside of nuclear power plants — major panoramic irradiators may contain 100,000+ curies of cobalt-60 (approximately Category 1 source activity × thousands of sources). The most dangerous irradiator accident scenario is a sealed source becoming separated from the facility (lost or orphaned) while remaining highly radioactive — a scenario that has resulted in serious radiation injuries and deaths in foreign countries (Brazil 1987 Goiânia; Mexico 1962). NRC's source security rules (10 CFR Part 37) apply to irradiator sources above Category 1 activity thresholds, requiring physical security programs, background checks for workers with access, and immediate notification of NRC if sources are lost or stolen.

Recent Rulemakings

• 2023 NRC amendment to Part 35 (final rule): Updated training requirements for authorized users of emerging radiopharmaceutical therapies including lutetium-177 DOTATATE (Lutathera, used for neuroendocrine tumors) and other targeted radiotherapy agents. Added provisions for electronic record maintenance. Addressed training for theranostics — combined diagnostic and therapeutic radiopharmaceuticals using the same molecule labeled with different isotopes for PET imaging vs. targeted therapy.
• Theranostics regulatory framework (2022–2026): The rapid commercial growth of targeted radioligand therapies (TRT) — including PSMA-targeted therapies for prostate cancer (Pluvicto/lutetium-177 vipivotide) and somatostatin-receptor therapies — has driven NRC and Agreement States to update authorized user training requirements and clarify which medical use categories cover these new agents.
• NRC inspection and enforcement of medical events: NRC publishes summaries of medical events (misadministrations) on its website. Common causes include wrong patient, wrong radiopharmaceutical preparation, equipment malfunction in brachytherapy afterloaders, and inadequate dose calibrator calibration. The NRC's Inspection Manual Chapter 2800 governs the inspection program for medical licensees.

Recent Developments

• Radioligand therapy (RLT) commercial growth: The FDA approvals of lutetium-177 vipivotide tetraxetan (Pluvicto) for prostate cancer in 2022 and lutetium-177 DOTATATE (Lutathera) for neuroendocrine tumors have driven a major expansion of targeted radioligand therapy in oncology. These treatments are typically administered in outpatient infusion settings, requiring Part 35 licenses and authorized user credentials at the treating facility. The commercial success of these agents has prompted hospitals and cancer centers to establish new radioligand therapy programs, significantly increasing demand for Agreement State and NRC licensing of new medical use facilities.
• Theranostics training standards update (2023): NRC finalized a Part 35 amendment in 2023 to address training requirements for authorized users of theranostic agents — radiopharmaceuticals that use the same molecular targeting mechanism for both diagnostic imaging (with a PET isotope) and therapy (with a beta or alpha emitter). The update clarified that authorized users must complete training specific to the therapeutic agent even if they already hold training for the diagnostic counterpart.
• Agreement State coordination: The majority of medical NRC licensing is handled by Agreement States (currently 39 states plus the District of Columbia and Puerto Rico) under Part 35 standards. The growth of new radioligand therapy programs has stressed Agreement State licensing capacity in some states, with processing timelines extending as new facility applications and authorized user credential reviews have increased.
• Alpha-emitter therapies (actinium-225): Next-generation radioligand therapies using actinium-225 (an alpha emitter with higher cytotoxicity than lutetium-177) are in late-stage clinical trials as of 2026. NRC is developing regulatory guidance for actinium-225 medical use, which presents different radiation protection considerations than beta-emitting agents (shorter range, no penetrating radiation but higher biological effectiveness). Supply chain constraints for actinium-225 are a parallel regulatory challenge under DOE's isotope production programs.

10 CFR Part 33 — Specific Domestic Licenses of Broad Scope for Byproduct Material: NRC's licensing framework for large institutions — research universities, government laboratories, major cancer centers — that handle a wide variety of radioactive isotopes and need the flexibility to acquire and use them without requesting NRC approval for each individual radionuclide or application. Without broad scope licenses, a research university where dozens of investigators use twenty different radionuclides would need a separate NRC amendment for each new isotope — making routine research impractical. Part 33 delegates routine approval authority to the institution's own radiation safety program, with NRC overseeing the institution-level program rather than individual uses.

Part 33 defines three tiers of broad scope license:

• § 33.11 — Types of specific licenses of broad scope: three tiers granting increasing institutional autonomy:
  • Type A — the most expansive tier: the licensee may acquire and use any byproduct material in quantities not exceeding Schedule A (§ 33.100) without case-by-case NRC approval. Requires a functioning Radiation Safety Committee (RSC) — composed of senior institutional officials, radiation safety expertise, and representatives of radioactive material users — that reviews and approves all uses, reviews incidents, and sets the institution's radiation protection policies. The RSO reports to the RSC and must have authority to immediately stop unsafe operations. Type A licenses are held by major research universities, DOE national laboratories, and large teaching hospitals.
  • Type B — intermediate tier: allows possession of any byproduct material in quantities not exceeding Schedule B (lower limits than Schedule A); requires an RSO and written radiation safety program but not a full RSC; appropriate for mid-sized institutions with significant but more focused radioactive material programs.
  • Type C — most limited broad scope tier: possession within even smaller Schedule B Column II quantities; fewer administrative requirements; designed for smaller research institutions with more routine radioactive material use.
• § 33.13 — Type A issuance criteria: NRC will issue a Type A license only if the applicant demonstrates: (1) a broadly based, independently administered radiation safety program; (2) an RSC with sufficient authority, resources, and membership to effectively govern radiation protection; (3) a qualified RSO with training and experience commensurate with the scope of activities; (4) a formal training program for radiation workers providing initial and annual refresher instruction; and (5) adequate facilities for the proposed activities.
• § 33.17 — Conditions applicable to all broad scope licenses: regardless of tier, all broad scope licensees must: use licensed material only for purposes stated in the license; ensure each authorized user has received instruction in hazards and safe procedures; maintain individual personnel monitoring for workers likely to receive doses above Part 20 thresholds; notify NRC of any RSO change within 30 days; and refrain from activities outside the geographic scope of the license without NRC approval.
• § 33.100 — Schedule A: lists approximately 270 radioactive isotopes with Column I and Column II quantity limits; common research radionuclides — hydrogen-3 (tritium), carbon-14, phosphorus-32, sulfur-35, iodine-125 — appear at high Column I limits reflecting decades of safe use in biochemical and biological research; more hazardous isotopes appear at lower limits with additional approval requirements.

The broad scope license is the practical foundation of radioactive material use at U.S. research universities. A Type A licensee may authorize hundreds of individual principal investigators to use dozens of different radionuclides across hundreds of laboratories — all under a single NRC license — with the institution's RSC and RSO serving as the internal regulatory body managing day-to-day approvals, training, and compliance. NRC's role shifts from per-use approval to program-level oversight: inspecting the institution's radiation safety program, reviewing annual reports, and investigating incidents rather than approving each new isotope acquisition.

Pending Action

(Left for wiki-enrich — NRC rulemaking on theranostics training standards and potential updates to release criteria for targeted radioligand therapies.)