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Nuclear Regulatory Commission (NRC) 

Advisory Committee on the Medical Use of Isotopes (ACMUI) 

Subcommittee on

Radioactive Seed Localization for Non-Palpable Breast Lesions 

Revision 1 

Submitted on August 11, 2015 

Subcommittee Members: 

Dr. Ronald Ennis (Chair) 

Dr. Philip Alderson 

Mr. Frank Costello 

Dr. Pat Zanzonico 

 

Introduction 

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

being performed in early 2000s. The first Guidance regarding RSL was issued by the NRC in 2006. 

This Subcommittee was formed in response to a request for modifications to the regulatory Guidance 

for RSL. The subcommittee 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 and analysis. The seed or seeds are then disposed of in accordance 

with 10 CFR 35.92 or the equivalent Agreement-State regulations. 
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Physical and dosimetric properties of iodine-125 seeds 

Iodine-125 seeds used for localization of non-palpable breast masses as well as for permanent-implant 

brachytherapy are comparable in size and shape to a grain of rice and are comprised of a doublewalled 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-Ci (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 trans-continental 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-Ci 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-Ci (0.3-mCi) and 

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

proportionately lower for lower activities and/or shorter time intervals. (The dose estimates based on 
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the assumption that the implanted seed was not removed and underwent complete decay in situ 

represent the doses for a rare, worst-case scenario.) In addition, it should be noted that 

OLINDA/EXM slightly overestimates the dose. 

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 Subcommittee and its 

Recommendations 

Title of Guidance

The subcommittee recommends that the title of the Guidance be changed by removing references to 

specific isotopes. The guidance is generic to any isotope used. Although I-125 is the most commonly 

used isotope to date, others could be used as well; so, there is no reason to specifically single out one 

or two isotopes. 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. Thus, the Guidance should be entitled “Low Dose Rate 

Brachytherapy Seeds Used for Localization of Non-palpable Lesions.” 

Similarly, references to I-125 and Pd-103 should be struck from the section headings “Safety 

Precautions and Instructions for Iodine-125 and Palladium-103 Seed Localization for Non-Palpable 

Lesions” and “Suggested Revisions to Existing Iodine-125 and Palladium-103 Seed Localization 

Programs to Conform to this Licensing Guidance” which should be changed to “Safety Precautions 

and Instructions for Brachytherapy Seed Localization for Non-Palpable Lesions” and “Suggested 

Revisions to Existing Brachytherapy Seed Localization Programs to Conform to this Licensing 

Guidance”, respectively. 
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Purpose 

The subcommittee recommends that 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 be deleted. 

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 feels that seeds can also 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 as follows: “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 subcommittee recommends that the following text in the Guidance 

be changed: from “Authorization 8: 1.5 millicuries maximum per treatment and 15 millicuries 

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

Authorized User 

Some radiologists who routinely place needles into breast or other tissue for the purposes of 

biopsies or placement of guidewires do not have the adequate training to be authorized users 

(AU) according to the current Guidance. The subcommittee acknowledges the difficulty in such 

a radiologist acquiring the needed training to be an AU once he/she has completed radiology 

training while also acknowledging the important knowledge and judgment acquired in such 

training to assure the safe use of radioactive materials in this setting. 

Regarding training, the subcommittee recommends that an AU under 10 CFR 35.290 be allowed to 

be supervised by a 10 CFR 35.290 AU who has been previously trained in RSL in addition to the 

option of supervision under a 10 CFR 35.490 AU. Thus, the AU section of the Guidance should 

state: 

The authorized user should be considered qualified for implementation, localization and removal of 

the seeds if the individual is listed on a license (NRC or Agreement State) and meets the criteria in: 

10 CFR 35.490 or the equivalent Agreement State regulations; or 

10 CFR 35.290, including supervised work experience under the supervision of a 10 CFR 

35.490 authorized user and preceptor or under the supervision of a 10 CFR 35.290 AU and 

preceptor who has previously been approved for RSL on an NRC or Agreement State 

license. Training and supervised work experience should include the following:...” 
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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 subcommittee feels that the work experience required for the AU should not include “removing 

RSL sources safely,” since this is performed by the breast surgeon. The subcommittee also feels 

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 

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 subcommittee feels 

the WD is an integral component of the proper regulatory requirements to assure safe RSL. 

Regarding the specific elements of a WD, The subcommittee feels that dose should be eliminated as 

one of the required elements of the pre-procedure 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 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 subcommittee, 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 

brachytherapy seeds 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 time planned before surgery.” 

The subcommittee 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. It 

should be noted, that if this is the result of the patient not showing up for the planned surgery, this 
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shall be considered “patient intervention” and not reportable as a Medical Event in accordance with 

10 CFR 353045. 

(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 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 subcommittee 

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, we recommend 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. In the event of seed rupture within the 

breast, the subcommittee recommends the patient be advised not to breast feed from that breast for 

10 half-lives. 

Verification of Source Activity 

Verification of source activity by the recipient is a crucial element of quality control and should 

remain in place. The subcommittee recommends, however, the following revision of the pertinent 

language in the revised Guidance: “The activity of sealed sources will be determined prior to each 

patient implant, either through direct measurement or based on manufacturer’s indicated activity after 

correcting for decay”. The foregoing language not only maintains consistency with the allowance to 

use the source manufacturer’s measurements for brachytherapy source activity in 10CFR35.432(3)(b) 

but also recognizes that the manufacturer-provided calibration of dose calibrators is not applicable to 

the physical configuration of prepackaged sterile seeds in needles. 

Training 

The subcommittee feels that training on topics described in §35.410 should not be required. These 

apply to brachytherapy procedure 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. The subcommittee, however, 

recommends the removal of mention of any specific devices but rather recommends the Guidance 

state “licensee should possess and use a portable, properly calibrated radiation survey instrument 

capable of detecting low dose rate brachytherapy seeds. Calibration of the device shall be performed 

as required for the proper use of the particular device. ” 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). 
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Performance of a radiation survey avoids any such potential confusion and should continue to be 

required. 

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 subcommittee feels 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 subcommittee 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. 

Respectfully submitted, August 11, 2015, 

Subcommittee on Radioactive Seed Localization for Non-Palpable Breast Lesions, 

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

Nuclear Regulatory Commission (NRC)