Diagnostic Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Limited data from two studies of technetium Tc-99m (Tc-99m) exposure in human pregnancy have not suggested an increased risk for the embryo or fetus. Although it is desirable to minimize ionizing radiation exposure during pregnancy, a radiopharmaceutical may be administered either in an unrecognized pregnancy or for urgent diagnostic reasons. In these situations, the radiation dose to the embryo–fetus is estimated to be well below the 5Gy limit of concern.
FETAL RISK SUMMARY
Tc-99m is a gamma-emitting metastable nuclear isomer of technetium-99. It is the most common radioisotope used in medical diagnostic procedures. It is available either in the pertechnetate soluble salt form or in complex with various other agents. These radiopharmaceuticals are administered orally, IV, or by inhalation to aid in diagnostic imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood, and tumors. The physical half-life (decay through gamma emission) of Tc-99m is approximately 6 hours, and the biological half-life is approximately 24 hours (1).
Animal reproduction studies with Tc-99m have not been conducted. Studies for carcinogenicity or mutagenic potential have not been conducted for most Tc-99m products. No genotoxic activity was observed for the active metabolite of Tc-99m sestamibi in various tests. At cytotoxic concentrations (>20 mcg/mL), an increase in cells with chromosome aberrations was observed in the human lymphocyte assay. No genotoxic effects in the in vivo mouse micronucleus test were observed at a dose that caused systemic and bone marrow toxicity (9 mg/kg, >600 times the maximum human dose). Fertility studies have not been conducted with Tc-99m (1).
Tc-99m is known to cross the placenta in animals and it is presumed that the same is true for the human placenta.
High-dose radiation exposure to the embryo or fetus is known to be associated with risks for intrauterine growth restriction, embryo–fetal loss, mental deficiency, and cancer. However, it is generally accepted that doses <5Gy to the embryo or fetus are not teratogenic. To evaluate potential risks for diagnostic procedures that utilize Tc-99m radiopharmaceuticals, estimates of the radiation dose available to the human embryo or fetus have been calculated under various scenarios, and these estimates are under the 5Gy limit. This suggests a low level of concern in situations where the diagnostic procedure is necessary in pregnancy or has been inadvertently performed in an unrecognized pregnancy (2–4).
In a 2009 study conducted by a German teratogen information service, 122 pregnancies were prospectively followed up in which the mothers were exposed sometime between the 2nd and 17th weeks of gestation to one of five Tc-99m radiopharmaceuticals for diagnosis of bone, thyroid, kidney, or lung conditions (5). Outcomes were compared with 366 unexposed pregnancies. No increased risks for growth deficiency, pregnancy loss, or major birth defects were noted in the exposed infants (5).
In a 1997 British study, data were abstracted from medical records for 82 pregnant women who had been evaluated for pulmonary embolism with either a Tc-99m perfusion or ventilation scan or both. Most scans were conducted late in pregnancy. No adverse pregnancy outcomes were reported, although no details were provided (6).
BREASTFEEDING SUMMARY
Tc-99m is excreted into breast milk. In a 1994 study, breast milk samples were obtained from 60 women who had been exposed to Tc-99m radiopharmaceuticals (7). Analysis found generally low radiation doses in breast milk across the samples, but there was distinct variability by specific radiopharmaceutical. Based on estimated dose, the recommendation for those products that produce the highest concentrations, such as Tc-99m pertechnetate, is to interrupt breastfeeding until activity in milk samples reaches a threshold concentration. For other products, no interruption in breastfeeding was considered necessary (8–10).
References
1.Product information. Technetium Tc 99m Sestamibi Injection, 2008.
2.Adelstein SJ. Administered radionuclides in pregnancy. Teratology 1999;59:236–9.
3.International Commission on Radiological Protection Pregnancy and Medical Radiation. Ann ICRP 2000;30:1–43.
4.Taskar-Pandit N, Dauer LT, Montgomery L, St. Germain J, Zanzonico PB, Divgi CR. Organ and fetal absorbed dose estimates from 99mtc-sulfur colloid lymphoscintigraphy and sentinel node localization in breast cancer patients. J Nucl Med 2006;47:1202–8.
5.Schaefer C, Meister R, Wentzeck R, Weber-Schoendorfer C. Fetal outcome after technetium scintigraphy in early pregnancy. Reprod Toxicol 2009;28:161–6.
6.Balan KK, Critchley M, Vedavathy KK, Smith ML, Vinjamuri S. The value of ventilation-perfusion imaging in pregnancy. Br J Radiol 1997;70:338–40.
7.Rubow S, Klopper J, Wasserman H, Baard B, van Niekerk M. The excretion of radiopharmaceuticals in human breast milk: additional data and dosimetry. Eur J Nucl Med 1994;21:144–53.
8.Rose MR, Prescott MC, Herman KJ. Excretion of iodine-123-hippuran, technetium-99m-red blood cells, and technetium-99m-macroaggregated albumin into breast milk. J Nucl Med 1990;31:978–84.
9.Marshall DS, Newberry NR, Ryan PJ. Measurement of the secretion of technetium-99m hexamethylpropylene amine oxime into breast milk. Eur J Nucl Med 1996;23:1634–5.
10.McCauley E, Mackie A. Breast milk activity during early lactation following maternal 99Tcm macroaggregated albumin lung perfusion scan. Br J of Radiol 2002;75:464–6.