Duration of Breastfeeding Interruption in Nuclear Medicine Procedures

DISCUSSION

Although a nursing mother who has received unsealed radioactive material can be released by a licensee if the total effective dose to any other individual exceeds 0.5 rem (5 mSv) in the United States, federal regulations (title 10 of Code of Federal Regulations, section 35.75) (10) require that the licensee must give guidance on the interruption or cessation of breastfeeding and information on the consequences of failure to follow the guidance if the dose to a breastfeeding infant or child could exceed 0.1 rem (1 mSv). Consequently, the recommendation on breastfeeding interruption from most guidance documents is based on the 1-mSv radiation exposure limit to the infant or child. However, infants and children are known to be about 3 times more sensitive to radiation than adults (11), and their vulnerability to radiation was considered when formulating the recommendations, usually with a conservative approach assuming a worst-case scenario (1,5,9).

Radiation exposure to a nursing child from a radiopharmaceutical administered to the child’s mother comes from both ingestion of radioactive maternal milk and external exposure from radioactivity in the mother. Generally, less than 10% of an administered radiopharmaceutical’s activity is excreted into breast milk; typical estimates range from 0.3% to 5% of the initial administered activity (2), depending on the radiopharmaceutical and physiologic factors. If breastfeeding were not discontinued, the doses from ingestion of radioactive milk to the newborn tissues (whole body or thyroid) could be calculated by summing the exposure from each feeding.

At our institution we follow the clinical procedure guidelines from the SNMMI and European Association of Nuclear Medicine (EANM); their recommendations on breastfeeding interruption are presented in the 4 tables. In general, SNMMI guidance documents are based on the consensus of experts from various fields, with consideration of scientific data from the ICRP, feasibility and convenience for patients, and the flexibility of the study. Consequently, the cutoff for breastfeeding interruption for some radiopharmaceuticals is loosely defined in their recommendations.

Stabin is well known for his work on dosimetry of radiopharmaceuticals, including studies on breast milk excretion. In the classic study of Stabin and Breitz on breast milk excretion (2), they provided not only the recommendations for 25 radiopharmaceuticals but also an understanding of radiation dosimetry, including breast anatomy, the physiology of lactation, a possible mechanism for breast milk excretion of radiopharmaceuticals, breast radiation exposure, and exposure to infants. Their recommendations are presented in the 4 tables.

The ICRP is a nongovernment organization that provides recommendations and guidance on protection against the risk associated with ionizing radiation. Societies such as the SNMMI depend on the ICRP for guidance. Because of its influence and impact on radiation safety protection, we present its recommendations in the 4 tables.

There are limited studies on breast milk excretion of radiopharmaceuticals. A recent study of activity concentration in breast milk from 53 breastfeeding patients after administration of 16 different radiopharmaceuticals has added new data to the field (1). The study provided estimates of absorbed doses to various organs and tissues and the effective dose to the infant. Consequently, the recommendations of this study are also presented in the 4 tables.

The ACMUI advises the U.S. Nuclear Regulatory Commission on policy and technical issues that arise in the regulation of the medical uses of radioactive material in diagnosis and therapy. A subcommittee on nursing mother guidelines for the medical administration of radioactive materials, led by experts in the field, provided updated recommendations for the nursing mother (10). For ^99mTc-labeled radiopharmaceuticals, rather than a radiopharmaceutical-specific interruption period, a single 24-h interruption period is recommended by the ACMUI. It argued that although this interval may be longer than necessary for some ^99mTc-labeled radiopharmaceuticals, the recommendation is compliant with the 0.1-rad dose limit and simplifies the guidance, thereby avoiding confusion and reducing the likelihood of error. Consequently, the ACMUI recommendations for most ^99mTc-labeled radiopharmaceuticals are different from other references and generally more conservative in terms of radiation risk.

There are differences in recommendations between our institution and other references shown in the tables for some radiopharmaceuticals. For ^99mTc-methyl diphosphonate, the SNMMI guidance document (7) is not definitive on the duration of breastfeeding interruption, with 2018 guidelines stating: “Per the International Commission on Radiological Protection, ^99mTc-labeled radiopharmaceuticals do not require any change in breastfeeding (unless ^99mTc-NaO₄ is present). Nevertheless, it may be recommended that the patient delay breastfeeding for a minimum of 4 h after receiving a ^99mTc-labeled radiopharmaceutical, and many institutions have the patient delay breastfeeding for 24 h.”

According to the EANM guidelines, whereas interruption of breastfeeding is not essential according to the ICRP, this is based on there being no free pertechnetate in the radiopharmaceutical. Therefore, an interruption of at least 4 h during which 1 meal is discarded is advised to be on the safe side. The ACMUI recommends 12 h for most ^99mTc-labeled radiopharmaceuticals for simplicity. On the basis of the available studies in the literature, and considering the possibility of free pertechnetate, which has been shown to be excreted in breast milk, we recommend a 4-h interruption of breastfeeding for ^99mTc-methyl diphosphonate, consistent with the guidance documents from the SNMMI and EANM.

It has been shown that ^99mTc-MAA and ^99mTc-pertechnetate have a higher breast excretion than other ^99mTc-labeled radiopharmaceuticals (1,2). For ^99mTc-MAA, it is speculated that “The individual variations in the initial ^99mTc concentrations and, likewise, in the total activities excreted in the breast milk were presumably caused by various amounts of ^99mTc-pertechnetate in the initial ^99mTc-MAA preparation, and by varied rates of breakdown of macroaggregate in the lungs.” (1). Consequently, for both ^99mTc-MAA and ^99mTc-pertechnetate we recommend a 12-h interruption whereas for other ^99mTc-labeled radiopharmaceuticals we recommend a 4-h interruption, consistent with most of the references in the tables.

For ¹²³I in the form of NaI (¹²³I-NaI), a shorter discontinuation period of 3 or 4 d is recommended by our institution and by the ACMUI than the earlier recommendation, which was based on the contamination (≤2.5% of the total activity) with long-lived ¹²⁵I (physical half-life, 60 d) that occurred with older methods of ¹²³I production (such contamination of ¹²³I with ¹²⁵I no longer occurs). Our recommendation of a 4-d interruption is similar to that of the ACMUI (3-d interruption) but much shorter than the recommendations of more than 3 wk from the ICRP (8) and the cessation recommended by Stabin and Breitz (2), thus significantly improving the prospect of resuming breastfeeding.

There is a significant difference in the recommendation for ¹¹¹In-oxine white blood cell scanning. Both Stabin et al. (2) and the ICRP recommended no cessation, whereas the ACMUI (10) recommends a 6-d interruption. Although the recommendation from the ACMUI was based on the data from Stabin and Breitz (2), the reported administered activity is quite different (185 MBq from Table 4 from the ACMUI and 18.5 MBq from Stabin and Breitz), probably because of a typographic error. On the basis of the original data from Stabin and Breitz, we have recommended no cessation. For ¹¹¹In-octreotide scanning, the SNMMI and ICRP recommend no cessation whereas the ACMUI recommends a 6-d interruption, based on the kinetic data from Castronovo et al. (5). In the study by Castronova et al., they measured the concentration of ¹¹¹In in breast milk in a 10-wk-postpartum woman at daily intervals up to 72 h after injection of 196.1 MBq (5.3 mCi) of ¹¹¹In-octreotide, with a conservative approach. They showed that if a newborn is nursed for the first 10 d, the internal and external dose equivalents would be 0.23 and 0.28 mSv, respectively, for a total of 0.51 mSv. The difference in recommendation was discussed with our working group, and until more data are available, we have decided to keep our recommendation of no cessation for the ¹¹¹In-octreotide scan. This test will soon be replaced with PET.

The external exposure from radioactivity in the mother to the infant could be significant, especially with high-energy photon radiopharmaceuticals (e.g., positron emitters). Despite common observations of increased breast ¹⁸F-FDG uptake in the lactating breast, ¹⁸F activity measured in breast milk was low (3), suggesting that the main source of potential radiation hazard to a breastfeeding infant is likely to be from the infant’s close proximity to the breast (external) rather than from ingestion of milk (internal). Consequently, patients should also be advised to avoid close contact with their children to reduce external radiation exposure. Our recommendation of breastfeeding interruption and avoiding close contact with the infant for 12 h is consistent with the SNMMI/EANM guidelines. The ACMUI recommended a 4-h interruption, possibly based only on the biokinetics of ¹⁸F-FDG and the absorbed-dose estimates for the lactating breast.

The mother should be advised to breastfeed the baby right before administration of the radiopharmaceutical and the interruption period. During this interruption, breast milk may be expressed at the usual feeding times and discarded or frozen for later use, depending on the circumstances. Afterward, breastfeeding can resume without concern. For an interruption period of longer than 3 wk, it may be difficult to resume breastfeeding. However, if the mother wishes to continue to breastfeed, she is advised to continue to express breast milk at the usual feeding times and discard it each time during these 3 wk.

There is a 2- to 5-fold increase in breast mass during lactation, and it is known that the lactating breast is sensitive to radiation. Except for ⁶⁷Ga-citrate and ¹³¹I-NaI, the highest absorbed dose estimates to the lactating breast for typical diagnostic administered activities are usually well under 0.01 Gy (1 rad). The absorbed dose to the lactating breast with a therapeutic administered activity of 4,000 MBq (108 mCi) of ¹³¹I-NaI was estimated to be 1.6 Gy (160 rad) (12). For lactating patients undergoing radioiodine therapy, we have followed the American Thyroid Association guidelines (13) and recommend discontinuing breastfeeding 3 mo before radioiodine ablation therapy to minimize the radioiodine concentration in the maternal breast and, thus, the absorbed maternal breast dose.