Radiopharmaceuticals

Perhaps no breastfeeding questions are as daunting for the generalist as questions about the safety of breastfeeding after receiving a radiopharmaceutical. Conceptually, radiopharmaceutical compounds are interesting to think about. Most medications are cleared from the bloodstream by the mother by renal excretion, hepatic metabolism, or both. If a drug is considered too toxic after maternal administration to allow breastfeeding, five half-lives is usually considered an appropriate time to wait before resuming breastfeeding. After five half-lives, a drug will be about 97% eliminated from the mother's body, and presumably the breastmilk. The half-life of a drug varies over a range, and most often the mean value is used for calculations.

Most radiopharmaceuticals consist of two parts: the radioactive isotope and a pharmacologically inert carrier molecule to which it is attached. The carrier molecule is designed to take the radiopharmaceutical to its intended target in the body by way of its physical or chemical properties, such as polarity, lipid solubility, receptor binding affinity, and so on. The hazard of radiopharmaceutical administration to nursing mothers is the exposure of the infant to radioactivity, usually not from any inherent toxicity of the carrier compound. In the case of radiopharmaceuticals, two routes of elimination of radioactivity are in play: the usual excretion and metabolism of the carrier compound with its own biological elimination half-life, and the radioactive decay of the isotope. The half-life of radioactive decay is an invariant physical constant of the isotope. LactMed reports the physical half-life of the radioisotope in the Drug Levels section of the drug record. Also reported in this section is the type of radioactive decay that the isotope undergoes.

If a radioactive element that has no interaction with tissues or organs in the body were given by itself without a carrier and were not eliminated by the body, one could easily predict with a high degree of certainty when the element would decay to an acceptable level. Radiologists typically use a value of 10 half-lives rather than 5 half-lives to consider the radioactivity to be completely eliminated. This corresponds to about 99.9% disappearance of the radioactive isotope. An extremely conservative time to wait after giving a radiopharmaceutical to a nursing mother would be 10 physical half-lives. This might be appropriate after administering an unbound radioisotope with no carrier, slow elimination, and known toxicity. However, with most radiopharmaceuticals, it is appropriate to calculate an “effective half-life,” which takes into account both the physical half-life of the radioactive isotope and the elimination half-life of the carrier compound.

Once the effective half-life of a radiopharmaceutical has been calculated, two other factors must be considered: the dose administered and the threshold for safe exposure of the infant. Most of the radiopharmaceuticals listed in LactMed are diagnostic agents and for most of these the dose varies over a small range. So, it is just a matter of applying the effective half-life to determine when radioactivity in the breastmilk will drop to a predetermined safe level. In general, diagnostic radiopharmaceuticals are designed to have short effective half-lives, because there is no advantage in their persistence after the completion of the diagnostic test. For a few diagnostic agents, different doses are used for different purposes. Therefore, higher doses require a longer waiting time. For radiopharmaceuticals with multiple recommendations based on dose, LactMed provides the data in a tabular format with dose and waiting time. A few commercially available compounds are used for therapy, usually cancer. These agents (e.g., tositumomab I-131) are given in high doses and usually require breastfeeding to be discontinued.

Determination of a safe exposure level can be quite complex and involves mathematical modeling of exposure of individual infant organs of concern. Fortunately for the clinician, these values have usually been agreed upon by radiological experts, who have also compiled waiting times based on the appropriate half-lives and exposure levels. The threshold that is generally used is exposure of the breastfed infant to an effective dose of 1 mSv (0.1 rem).^1–3 The United States Nuclear Regulatory Commission (NRC) and International Commission on Radiological Protection (ICRP) have published compilations of waiting times.^2,4 European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine (SNM) have also published numerous guidelines for specific radiopharmaceuticals or procedures. Unlike other drug records, LactMed usually does not cite individual case reports of excretion into breastmilk, but reports these expert guidelines for waiting times. NRC, ICRP, EANM, and SNM guidelines usually agree closely, but occasionally they diverge because of different assumptions concerning safe infant exposure levels or possible contamination with other radioisotopes that are created in the production or decay of the original isotope. LactMed generally does not “take sides” when guidelines diverge, but rather reports recommendations from all guidelines.

In addition to exposure through breastmilk, some radiopharmaceuticals can expose persons near to the mother to radiation across a distance. The likelihood of this depends largely on the type of radioactive decay that the isotope undergoes. For example, alpha particles have a very short range and generally are not a concern for external radiation, whereas high energy gamma radiation can be a problem. The exposure of radiation to the child coming directly from the mother can be reduced in three ways: (1) The dose that the infant receives is proportional to the time that the exposure takes place; reducing the time in half reduces the exposure by half. (2) Radiation exposure falls with the square of the distance between mother and infant; twice the distance reduces exposure fourfold; (3) Shielding—the amount of protection depends on the material, its thickness, and the type of radiation that is characteristic for each radioisotope. NRC and other guidelines are available that indicate the period of time that mothers should not come in close contact with their infants for various radiopharmaceuticals. Information from these guidelines is found in the “Summary of Use during Lactation” section of LactMed. Absence of this information in the LactMed record generally indicates that proximity to the mother is not of concern.

When patients ask about radiopharmaceutical use during breastfeeding, it is typically in the form of, “I need to have a technetium scan, will it be OK to breastfeed afterwards?” To use LactMed effectively, a number of important pieces of information should be elicited. Many radiopharmaceuticals have a dizzying array of synonyms that can be confusing for those who are not nuclear medicine specialists. So, the name of the radiopharmaceutical and dosage must first be ascertained. LactMed uses the official United States Adopted Name of the radiopharmaceutical as the record name, but includes (hidden) cross-references to synonyms so that the record can be located. LactMed also lists the most common chemical names and abbreviations in the body of the record as a cross-check for the user. LactMed currently has 25 records on technetium Tc99m-containing agents. Sodium pertechnetate Tc99m is a small molecule that passes readily into breastmilk and can concentrate in the infant's thyroid. It requires up to 24 hours of nursing cessation with high doses and slow elimination, but only 4 hours with low doses and rapid elimination. Some other technetium agents require no cessation of nursing. Another common question is with regard to “radioactive iodine.” Determining the exact isotope that will be used is critical, because even a small dose of I-131 will require the mother to permanently stop nursing this child, whereas a low dose of I-123 may require little or no interruption of nursing. LactMed lists alternatives to radioiodine-containing agents for some uses.

The timing of the examination is also important. If a scan is scheduled for several days in the future, the mother can pump extra milk and store it to give to the infant during the waiting period after administration of the radiopharmaceutical. Another consideration is that milk pumped during the waiting period can usually be stored and used later, with the storage duration dependent on radioactive isotope's half-life, because the radioactivity will decay during the storage period. Finally, if concern exists after the examination, the mother's pumped milk can be easily tested for radioactivity levels at the facility that performed the examination. ⁵