Estimation of the β+ Dose to the Embryo Resulting from ¹⁸F-FDG Administration During Early Pregnancy

MATERIALS AND METHODS

The patient, a 27-y-old woman weighing 60 kg, was referred to our department for follow-up of Hodgkin's lymphoma. The lymphoma had been diagnosed 2 y previously and treated with chemotherapy and radiotherapy. Because a residual mediastinal mass persisted on CT, the patient was considered to be in complete remission, unconfirmed. She had been pregnant the previous year and was referred for verification of the residual mass a few months after delivery.

Imaging was done with a Gemini PET/CT device (Philips) and started 1 h after injection of 320 MBq of ¹⁸F-FDG. Patients are asked to urinate just before imaging begins.

The Gemini PET/CT system consists of an Allegro 3-dimensional PET scanner in line with an Mx8000 EXP dual-slice CT system. The latter is programmed to acquire a low-dose CT scan (120 kV, 40 mAs/slice). No contrast medium was injected. PET image reconstruction used a 3-dimensional RAMLA algorithm. PET images were corrected for attenuation, scattered coincidences, and random coincidences.

On review of the images, and from information collected later, the patient was found to be pregnant. Ultrasound examination indicated that the embryo had been 55 d old (±3 d) at the time of the PET/CT examination.

For the dosimetry assessment, we focused on the 3 components of the embryo dose (β+ dose, photon dose, and CT dose).

RESULTS

Figures 1A and 1B show a transaxial and a sagittal slice, respectively, through the uterus. The embryo is indicated by an arrow.

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FIGURE 1. 

Transaxial (A) and sagittal (B) ¹⁸F-FDG PET (left) and CT (right) slices through uterus. Embryo is indicated by arrow.

The mean SUV in the embryo was 2.2. The maximum SUV was 2.7. This maximum SUV of 2.7 was found in 2 successive slices. After correction for the partial-volume effect (4), the corrected mean SUV was also 2.7, matching the maximum SUV of the uncorrected images. We thus used the SUV of 2.7 to derive the total number of disintegrations occurring in the embryo. The mean corrected SUV for intrauterine amniotic fluid was 1.1.

DISCUSSION

The absorbed dose from internal emitters is a major preoccupation (22), especially in the case of developing organs and tissues, which show increased radiosensitivity (2). Estimation of the specific absorbed doses to the embryo and fetus from radionuclide exposure of the mother is a challenging task. In the case of ¹⁸F-FDG administration to a pregnant woman, the dose to the fetus is given by the sum of photon emissions (principally deriving from maternal tissues) and the β+ dose (mainly absorbed as the self-dose).

Although the photon dose can be realistically approximated by using phantoms and mathematic models, fetal self-irradiation is more difficult to estimate. Data on radionuclide uptake by the embryo or fetus are rare, as they can be obtained only after accidental exposure or by extrapolating the results of animal experiments (1,23).

Our results suggest that the dose received by an 8-wk embryo is about 3.3E−2 mGy/MBq. This is higher than the dose estimated by Stabin (24), who reported a value of 2.2E−2 mGy/MBq up to the third month of pregnancy (and 1.7E−2 mGy/MBq in later pregnancy). This difference results from a higher estimate of the β+ contribution. We found that the β+ self-dose (1.8E−2 mGy/MBq) represented a major component of the total ¹⁸F-FDG dose in embryos (55% here).

Stabin made the assumption that the average concentration of ¹⁸F-FDG was the same in fetal tissues as in the mother (24). This assumption was based on a report by Benveniste et al. of similar ¹⁸F-FDG uptake in primates, as measured by mother–fetus SUV ratios (23). However, our data suggest that, at least in early pregnancy, uptake of ¹⁸F-FDG by human embryo tissues is higher.

Besides differences between nonhuman-primate and human physiology, this discrepancy may be explained by the following 3 considerations: First, the nonhuman-primate fetuses in the study by Benveniste et al. were at a later stage of development than was the human embryo described here (the youngest nonhuman-primate fetus was in the early second trimester). The embryonic phase is the main period of organogenesis, characterized by a rapid mass increase (7). Generally, higher cell proliferation is associated with more glucose consumption. Second, glucose is the principal energy substrate for the embryo and fetus. Its uptake is regulated by the expression of glucose transporters on the plasma membrane of embryonic cells (25). Third, the nonhuman primates in the study by Benveniste et al. were anesthetized with high doses of propofol (200–300 μg/kg/min), which is known to cross the placenta (26) and may possibly influence ¹⁸F-FDG uptake by the fetus.

For our estimation, we assumed that the SUV recorded 1 h after the injection was representative of the average concentration in the embryo over time. This was a necessary approximation, as we do not know the kinetics of ¹⁸F-FDG in embryo tissues.

We may have underestimated the real dose to the embryo from positrons: At this stage of pregnancy, the embryo is constantly moving in amniotic liquid, potentially leading to an underestimation of SUVs on PET images.

Moreover, the tracer distribution within the embryo is probably heterogeneous, even if, given the spatial resolution of the PET scanner used here, SUVs on the images appeared homogeneous. Thus, our study does not address the possibility of heterogeneous distribution of the dose at a microscopic level. Our work gives an estimate of the dose to the embryo per megabecquerel of ¹⁸F-FDG if this examination is performed out of necessity during early pregnancy or in cases of accidental exposure.

Our patient received 320 MBq of ¹⁸F-FDG, and the resulting radionuclide dose to the embryo was 10.6 mGy. After adding the dose of the unenhanced CT scan (8.3 mGy), we estimated that the total dose was 18.9 mGy. This dose remains well within the range of “safe” levels (27). Steenvoorde et al. reported that, at this stage of pregnancy, the risk to the embryo of malformation is about 0.05%/mGy, with a suggested threshold of 100 mGy. Growth retardation occurs after a threshold of 50–250 mGy (27). It remains, however, that combined PET/CT examinations result in a relatively high dose. The CT component of the dose depends on the characteristics of the scanner and increases if high-quality, contrast-enhanced CT is used (15). For example, CT doses to the uterus can vary by a factor of 5, depending on the scanner and protocol (28).

In a patient with a history of cancer, the relative risks from radiologic studies are to be considered along with those from other, more immediately hazardous exposures such as chemotherapy (29). Our patient had been pregnant on a prior occasion about 1 y after the completion of therapy for lymphoma, and the outcome of that pregnancy was normal. When a new pregnancy was discovered after the PET study, the patient was counseled that radiation risk was below the safety threshold; no specific recommendation was made. The patient delivered at term a healthy baby.

CONCLUSION

Uptake of ¹⁸F-FDG by embryo tissues in early pregnancy may be higher than previously postulated. Our data suggest that the embryo dose in early pregnancy is at least 3.3E−2 mGy/MBq administered to the mother. About 55% of this dose comes from positrons.

Because our data involve only 1 subject, they do not necessarily suggest a change in currently reported standard values (24). As other data become available in the future, the average from these studies may be used to establish a new recommended dose value.