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University of Pittsburgh School of Medicine Pittsburgh, Pennsylvania
TO THE EDITOR:
We are using PET with 11C-WAY 100635 and 11C-raclopride (sequentially) to measure brain serotonin-1A and dopamine-2 receptor binding, respectively, in depressed and nondepressed postpartum research subjects. We received permission from our Institutional Review Board and Radioactive Drug Research Committee to scan lactating women with 2 provisions: that the subjects express their breast milk after each scan for analysis of radioactivity and cold WAY 100635 and raclopride content, and that the subjects nurse their infants no sooner than 200 min (i.e., 10 times the half-life of 11C) after the final radiopharmaceutical injection.
Five lactating women underwent 11C-WAY 100635 (1) and 11C-raclopride (2) PET according to methods previously described. The 11C-WAY 100635 injection was followed by 90 min of scanning. Sixty minutes later, 11C-raclopride injection was followed by 60 min of scanning. Approximately 15 min after the conclusion of each scan, study participants expressed their milk with a multiuse electronic double-breast pump (Medela, Inc.) for 1030 min. The mean subject age (±SD) was 27.4 ± 6.9 y; the range was 2036 y. The mean infant age was 9.4 ± 3.4 wk; the range was 413 wk.
The radioactivity content of breast milk was measured for both radiotracers. The mean activity concentration of 11C in breast milk (455 ± 107 Bq/mL) was similar to that in plasma (355 ± 99 Bq/mL) 60 min after 526 ± 61 MBq of 11C-WAY 100635 had been injected. For 11C-raclopride, the mean activity concentration of 11C in breast milk (105 ± 32 Bq/mL) was significantly less than that in plasma (913 ± 361 Bq/mL) 60 min after radiopharmaceutical injection (384 ± 24 MBq).
A commonly used model was applied to predict the radioactive dose to an infant through breast milk after the mother had received an injection of tracer for PET (effective dose = activity in breast milk [Bq/mL] at 60 min x 100 mL x effective dose for a newborn from OLINDA/EXM (3) using generic biokinetic model for 11C brain receptors in addendum 6 to ICRP 53 [0.0594 mSv/MBq] (4)). We chose a worst-case model that assumed an infant weight of 3.4 kg (10th percentile for a 1-mo-old infant (5)), rapid breast milk uptake from the gut (immediate absorption and distribution through the body), and breast milk intake as early as 60 min after tracer injection, in the event the subject could not tolerate the scan procedure. The model also assumed that other drug exposures were absent and that 100 mL of breast milk were consumed within a feeding. In this model, the mean radioactive dose to the nursing infant at 1 h was 2.7 ± 0.6 µSv after 11C-WAY 100635 and 0.6 ± 0.2 µSv after 11C-raclopride injection. Because the mean dose from breast milk for each radioligand was under the limit identified for radiation protection of the general population (1 mSv/y) (and also well under the daily exposure to background radiation in the environment), we concluded that interruption of breastfeeding was not warranted.
Breast milk samples were also assayed for cold WAY 100635 and raclopride content by the method of standard addition, so that each sample served as its own matrix. WAY 100635 and raclopride concentrations were measured with high-performance liquid chromatography using ultraviolet detection, as previously described (6). Neither WAY 100635 (detection limit, 1 ng/mL) nor raclopride (detection limit, 5 ng/mL) was detectable in any of the samples. WAY 100635 and raclopride metabolites were also undetectable, assuming detection limits similar to those of the parent compounds.
Because of concerns about transmission of radioactivity to infants through breast milk, lactating women are generally excluded from research protocols that administer radiopharmaceuticals. These data demonstrate negligible radioactivity and cold ligand in breast milk after 11C-WAY 100635 and 11C-raclopride brain PET imaging in our laboratory and, thus, negligible risk to breast-fed, healthy infants who are 413 wk old, weigh at least 3.4 kg, and have no other drug exposures. These data also demonstrate that lactation can proceed without interruption in such studies. These findings support removing an important barrier to neurobiologic research in lactating women and may be most relevant to studies of postpartum mental health and the neurochemistry of lactation. Future work must also examine how the inclusion of lactating women within samples of the general female population might influence outcomes of interest because of the potential neurobiologic effects of oxytocin and prolactin.
REFERENCES
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