1 of 7

Nuclear Regulatory Commission (NRC)

Advisory Committee on the Medical Use of Isotopes (ACMUI)

Sub-Committee on

Radioactive Seed Localization for Non-Palpable Breast Lesions

Sub-Committee Members:

Dr. Ronald Ennis (Chair)

Dr. Philip Alderson

Mr. Frank Costello

Dr. Pat Zanzonico

Draft Report Submitted on May 29, 2015

Introduction

Radioactive seed localization (RSL) is a relatively new medical procedure, the first such procedures 

being performed in the early 2000s. The first Guidance regarding RSL was issued by the NRC in

2006. This Sub-committee was formed in response to a request for possible modifications to the 

regulatory Guidance for RSL. The Sub-committee also felt enough time had elapsed since the initial 

issuance of the Guidance to warrant a review of the Guidance.

Background

The main current use of RSL is in localization of non-palpable breast lesions prior to surgical 

excision, although other indications are emerging. In the breast, RSL is an alternative to the 

traditional localization procedure to guide breast surgery, wherein a non-radioactive radio-opaque

percutaneous wire is implanted into the lesion and excised with the suspicious tissue. The RSL 

technique offers the following main advantages over the wire-implantation technique: scheduling is 

more flexible, as RSL can be performed up to a week (or longer) before surgery; wires protruding 

from the skin, which some patients find disconcerting, are avoided; and cosmesis is potentially 

improved, as the surgeon can place the incision at the optimal location and is not restricted to the 

sites of the localization needles.

RSL uses the same radioactive seeds as those used for brachytherapy. Iodine-125 or palladium-103 

seeds (typically only one but as many as four) containing 200-300 μCi each are implanted 

percutaneously by a radiologist under image (mammography or ultrasound) guidance into the breast 

lesion using a needle; iodine-125 seeds are used far more commonly than palladium-103 seeds. The 

surgical procedure and removal of the seeds are typically performed 2 to 7 days post-implantation, 

although seed implantation is sometimes performed on the same day as the surgical procedure. The 

radioactive seed(s) and thus the lesions can be localized with an intraoperative gamma probe 

identical to that use for sentinel node biopsy and surgically removed. The seed(s) may be removed 

from the tissue specimen in surgery or, more commonly, the tissue specimen containing the seed(s) 

are sent to Pathology for removal of the seed(s) and analysis. The seed or seeds are then disposed of 

in accordance with 10 CFR 35.92 or the equivalent Agreement-State regulations.
2 of 7

Physical and dosimetric properties of iodine-125 seeds

Iodine-125 seeds used for localization of non-palpable breast masses as well as for permanentimplant brachytherapy are comparable in size and shape to a grain of rice and are comprised of a 

double-walled titanium capsule containing an iodine-125-containing carbon-based material coating 

a radiographically imageable tungsten marker (See the figure below).

Iodine-125, with a physical half-life of 60.1 days, decays by electron capture accompanied by the 

emission of low-energy gamma rays and a cascade of characteristic x-rays ranging in energy from 

~4 to ~45 keV; its most abundant photon emissions (3 x-rays with a collective abundance of 128%)

are in the energy range 27-31 keV. Its overall half-value layer is only 0.02 mm in lead and 1.7 cm 

in water or soft tissue. Its gamma constant is 0.27 mR/h/mCi at 1 m, yielding an exposure rate from 

a 300-μCi (0.3-mCi) iodine-125 seed of ~0.081 mR/h at 1 m. Therefore, the absorbed dose at 1 m 

from such an iodine-125 seed would be only 58 mrad if an implanted seed were not removed (i.e.,

for complete decay) and only 7 mrad if the seed were removed 7 days post-implantation, assuming 

the seed was implanted at a depth of 1.7 cm (or 1 half-value layer) in the breast; the actual doses to 

individuals at 1 m from the patient would be 15 and 1.8 mrad, respectively, assuming the standard 

occupancy factor value of 0.25 for such individuals. The corresponding absorbed doses at 0.3 m 

(approximating the position of a child being held by the patient, for example) would be 640 and 78 

mrad, respectively; the actual doses to a held child at 0.3 m would be 130 and 16 mrad, 

respectively, assuming an occupancy factor of 0.2 for such a child. Realistically, therefore, the 

absorbed doses from a patient implanted with an iodine-125 seed for localization of a breast lesion 

are extremely low, of the order of those received by passengers over the course of a transcontinental airline flight or less. Accordingly, there is no need for the patient or her family 

members to follow any radiation safety precautions in the time interval between seed implantation 

and explantation.

The radiation doses to a patient implanted with a 300-μCi iodine-125 seed may be estimated using 

the OLINDA/EXM computer code. If an implanted seed were not removed (i.e., for complete 

decay), the mean absorbed dose to the breasts would be 120 rad and the effective dose 6.1 rem; the 

absorbed doses to tissues other than the breasts would of the order of 1 rad or less. However, the 

doses to the tissue immediately adjacent to the seed(s) would be substantially higher than this. If 

these tissues are not subsequently excised at surgery along with the seed(s), long term consequences 

such as fibrosis are possible. More realistically, if the seed were removed 7 days post-implantation, 

the mean absorbed dose to the breasts would be 5 rad and the effective dose 0.23 rem; the absorbed 

doses to tissues other than the breasts would less than 0.1 rad. Importantly, the foregoing first-order 

dose estimates are conservative in that they assume a maximal seed activity of 300-μCi (0.3-mCi) 

and maximal time interval of 7 days from implantation to explantation. The actual doses would be 
3 of 7

proportionately lower for lower activities and/or shorter time intervals. (The dose estimates based 

on the assumption that the implanted seed was not removed and underwent complete decay in situ 

represent the doses for a rare, worst-case scenario.) 

Iodine-125 seeds for localization of non-palpable breast masses are packaged in a sterile pre-loaded 

needle assembly (See the figure below) and are thus ready-to-use. The available needle lengths are 

5, 7, 10, and 15 cm and the seeds themselves are shielded by a lead or steel sleeve. Once the shield

is removed and the tip of the needle percutaneously positioned in the lesion, as guided by 

mammographic or ultrasound imaging, the plunger cover is removed and the plunger pushed to 

implant the seed within the lesion. As marketed, the seed and needle assembly have a shelf life of 

90 days; this is dictated not by the physical decay of the iodine-125 but rather by the sterility of the 

assembly. The supplier of the iodine-125 seeds can, and should, provide the Sealed Source and 

Device Registry (SSDR) certificate.

Changes to Guidance Considered by the Sub-committee and its 

Recommendations

Title of Guidance

No change in the title of the Guidance is recommended. Although the sources are not being used for 

therapy, they are commonly called “brachytherapy sources.” Therefore, the use of that term in the 

title is only meant for clarity and not to imply this is a brachytherapy procedure. In addition, 

although Pd-103 has not been used to date for this procedure, the Sub-committee sees no reason to 

exclude this isotope and therefore recommends retaining the reference to it in the title.

Purpose

The wording in the beginning of this section should be modified to address the current use of RSL,

which includes possible non-breast (e.g., axilla) applications, as follows: 

“The purpose of radioactive seed localization (RSL) of non-palpable lesions is to localize suspicious 

tissues for excision with the use of radioactive seeds. Most commonly, this is being used in the 

breast where RSL differs from current localization procedures...”

Footnote #1 should also be deleted.
4 of 7

Waste Disposal

The Guidance currently states: “The seed or seeds are then disposed of in accordance with 10 CFR 

35.92 or the equivalent Agreement State regulations.”

The Sub-committee agrees that seeds can be returned to the supplier following proper procedures 

and do not have to be retained at the facility that used them. Therefore, this sentence should be 

modified to state the following:

“The seed or seeds can be returned to the supplier following proper procedures or disposed of in 

accordance with 10 CFR 35.92 or the equivalent Agreement State regulations.”

General

Radionuclides, Form, Possession Limits

Since RSL is not a treatment, the following text in the Guidance should be changed: 

“Authorization 8: 1.5 millicuries maximum per procedure and 15 millicuries total,”

Authorized User

Seed placement must be performed by the Authorized User (AU) as defined in the existing

Guidance. The Sub-committee considered changes to this requirement, but feels that the proper 

handling of the radioactive source used in this procedure require this level of expertise in radiation 

protection. 

For clarity, in the AU section of the Guidance that begins, “Pathology personnel...”, the following 

statement should be added “This training should be provided by the AU described above or the 

Radiation Safety Officer, as applicable.” This would provide consistency between pathology and 

surgical personnel with respect to the requisite radiation safety training.

The Sub-committee agrees that the work experience required for the AU should not include

“removing RSL sources safely,” since this is performed by the breast surgeon. The Sub-committee 

also agrees that radiation safety training for surgeons working under the supervision of the AU

should not include preparing and implanting brachytherapy sources, since these procedures are not 

performed by the surgeon.

Written Directive

The Sub-committee also considered a request to remove the requirement for a Written Directive

(WD) for RSL. Pursuant to §35.40, a WD is required when a therapeutic dose of byproduct 

material is being delivered. Although the goal of the procedure is guidance of surgery rather than 

therapy, from the perspective of patient safety these sources may deliver doses considered to be in 

the therapeutic dose range close to the source or when left in for long periods of time. Therefore, 

the Sub-committee feels the WD is an integral component of the proper regulatory requirements to 

assure safe RSL. The Sub-committee does agree, however, with the suggestion to modify the 

specific elements of the WD and to eliminate dose as one of the required elements of the preprocedure WD. In addition, the language of the requirement regarding the location into which the 

seed will be implanted should be modified from “treatment site” to “implant site,” consistent with 

the non-therapeutic intent of RSL. Thus, prior to the procedure, the WD must specify the implant 
5 of 7

site (i.e., location within patient’s body), the radionuclide to be used and the activity of the source. 

The post-procedure part of the WD must specify the implant site, radionuclide, number of sources 

implanted, total activity implanted and total time planned until surgery. If a violation of the WD

occurs, a report must be completed as required in §35.3045.

The Sub-committee, therefore, recommends the following language in the revised Guidance:

A written directive must be dated and signed by an authorized user before the administration of I125 or Pd-103 for seed localization. The written directive must contain the patient or human 

research subject’s name and the following information –

(i) Before implantation: implantation site, the radionuclide, and activity per source; and

(ii) After implantation, but before completion of the procedure: the radionuclide, implantation site, 

number of sources, and total activity implanted and exposure time/time planned before surgery.

Medical Event Reporting

The Sub-committee also recommends the following language in the revised Guidance:

Medical Event Reporting -

(a) A licensee shall report any event, except for an event that results from patient intervention, in 

which the administration of byproduct material or radiation from byproduct material results in-

(i) An administration of radioactive byproduct material to the wrong individual or human research 

subject;

(ii) An administration of the wrong radioactive byproduct material;

(ii) An administration of the radioactive byproduct material to the wrong site (part of body)

(iii) Administration of radioactive byproduct material for more than 20% longer than planned

(iv) An administration of the radioactive byproduct material activity of more than 20% of the 

intended activity

(v) A leaking sealed source.

(b) A licensee shall report any event resulting from intervention of a patient or human research 

subject in which the administration of byproduct material or radiation from byproduct material 

results or will result in unintended permanent functional damage to an organ or a physiological 

system, as determined by a physician.

Safety Precautions

The Sub-committee feels the precautions regarding source rupture or cutting are warranted, as such 

incidents have been reported. In addition to written emergency procedures for such an occurrence, 

the Sub-Committee recommends written emergency procedures be required for other abnormal 

situations including: loss of a seed, implant of a seed in the wrong location or wrong patient, 

inability to locate an implanted seed during surgery or pathological processing, and if a patient 

implanted with a radioactive seed does not present for scheduled surgery. Finally, the Subcommittee recommends patients be advised not to breast feed from a breast into which a seed(s)

has(ve) been implanted and not yet removed. Breast feeding is, of course, permissible once the 

seed(s) has(ve) been removed.

Verification of Source Activity

Independent verification (i.e., assay) of source activity by the recipient is a crucial element of 

quality control and should remain in place. 
6 of 7

Training

The Sub-committee agrees that training on topics described in §35.410 should not be required. 

These apply to brachytherapy procedures after which the patient cannot be released from the 

medical facility; this does not apply to RSL.

Survey Instrumentation and Radiation Survey Requirements

Seed removal is required to be verified on the basis of a radiation survey using a sodium iodide 

(NaI) or Geiger-Muller (GM) meter. While imaging, such as a specimen radiograph or ultrasound, 

can visualize a seed as well, confusion could arise if the patient has also had the placement of items 

such as surgical clips prior to this procedure (e.g., at the time of biopsy). Performance of a radiation 

survey using a NaI or GM meter avoids any such potential confusion and should continue to be 

required. The Sub-committee does recommend, however, that the preference for NaI meter over a 

GM meter be removed from the Guidance, since both are effective for this task given that the I-125 

activities used for RSL are easily detected by both types of meters. The Sub-Committee also agrees

that annual calibration of the survey meter is not required for the purpose of verifying seed removal, 

since the meter is used in this context simply for source detection and not, for example, for a 

exposure-rate measurement.

Change in Physical Conditions of Use

This section should be modified as follows, given that the radioactive seeds are currently approved 

by FDA for localization procedures:

If the physical conditions of use exceed those reported in the Sealed Source and Device (SS&D) 

certificate, the limited specific medical use licensee should request an amendment for the new 

conditions, and a broad scope licensee should perform its own engineering and radiation safety 

evaluation addressing those differences.

Procedures

The Sub-committee agrees that the procedures described in §35.410 are not necessary, since 

patients are always released from the medical facility following RSL. These procedures should be 

removed from the Guidance.

The Sub-committee also feels that §35.41 should be changed to §35.41 (a), (b) (1), (2), (c), 

excluding §35.41 (b) (3) and (b) (4), which require dose calculations. 

In addition, §35.432 should be changed to include only 35.432 (a) and (c) because (b) allows the 

licensee to rely on source strength measurements provided by the manufacturer. The Sub-committee 

believes, as stated elsewhere in the guidance , that the licensee must make their own measurement 

to verify source strength.

Therefore, the language in the guidance should be modified to state the following:

Because the iodine and palladium seeds are temporarily implanted, the applicant may simplify its 

submission by confirming that it will:
7 of 7

Meet the requirements for temporary implants and develop, implement, and maintain the 

appropriate procedures in the following regulations: 10 CFR 35.40(a), (c), (d), and as modified 

above in the Written Directions Section, 35.41(a), (b)(1), (b)(2) and (c), 35.67, 35.75, 35.310, 

35.404, 35.406, 35.432(a) and (c), or the equivalent Agreement State regulations.

Respectfully submitted, May 29, 2015,

Sub-Committee on Radioactive Seed Localization for Non-Palpable Breast Lesions,

Advisory Committee on the Medical Use of Isotopes (ACMUI),

Nuclear Regulatory Commission (NRC)