Abstract
Background: The use of 201Tl in myocardial perfusion single-photon emission computed tomography (SPECT) is predominantly not recommended because of the higher radiation exposure of 201Tl compared to 99mTc agent. However, the advent of new gamma cameras with semiconductor detectors has made it possible to reduce the 201Tl dose and lower radiation exposure. In our hospital, the dose of 201Tl is adjusted according to the patient's body mass index (BMI), with 50 MBq for BMI<25 and 74 MBq for BMI≥25. The dose of 201Tl during simultaneous acquisition dual-isotope myocardial perfusion SPECT (MPS; stress 201Tl and rest 99mTc agent) exceeds 9 mSv/examination when 74 MBq of 201Tl is administered. In order to further reduce the radiation dose, optimization of the 201Tl dose was investigated.
Methods: Two hundred and eighty consecutive patients who underwent stress MPS using simultaneous acquisition dual-isotope protocol (SDI protocol) for the estimation of ischemic heart disease were included. Patients with prior myocardial infarction were excluded. Correlations between BMI and acquisition time were determined in patients receiving 50 MBq (n=154) or 74 MBq (n=126) of 201Tl. In addition, linear regression analysis was used to determine the slope and intercept to derive a linear functional equation, and the theoretically optimal 201Tl dose was evaluated.
Results: The correlation coefficient between BMI and acquisition time in the 201Tl 50 MBq group was 0.532 (P < 0.00001) and in the 201Tl 74 MBq group was 0.478 (P < 0.00001), both showing a positive correlation. Linear regression analysis yielded two equations: y=0.52x-0.32 (201Tl 50 MBq group) and y=0.41x-0.69 (201Tl 74 MBq group). Linear function equation results indicated that patients with BMI between 25 and 30 could be examined within approximately 15 minutes with 50 MBq of 201Tl.
Conclusion: Considering examination efficiency, a single acquisition time of less than 15 minutes is ideal. Theoretically, patients with BMI less than 30 could be examined within approximately 15 minutes with 50 MBq of 201Tl.
The ratio of 201Tl to 99mTc for stress myocardial perfusion single-photon emission computed tomography (SPECT) in Japan was approximately 1:1 in 2016, which is a higher ratio than in United States and Europe (1). However, 201Tl has a higher radiation exposure than 99mTc, and the IAEA Nuclear Cardiology Protocols Study (INCAPS) study suggested that patients under 70 years of age should not be examined with 201Tl (2). The American Society of Nuclear Cardiology has proposed that more than 50% of all examinations should be performed with an radiation dose of 9 mSv or less (3). However, 201Tl is known to have better extraction fraction of blood flow and higher sensitivity in detecting ischemic myocardium compared to 99mTc (4). In addition, it has been reported that 201Tl improves the diagnostic performance of multi-vessel lesions by measuring washout rate (5). Recently, the advent of semiconductor gamma cameras (D-SPECT) has made it possible to reduce the dose of radioisotope tracer (especially, 201Tl) and reduce radiation exposure (6, 7). We use the simultaneous acquisition rest 99mTc/stress 201Tl dual-isotope myocardial perfusion SPECT (MPS; SDI protocol) reported by Makita and Sugai et al. in our hospital and adjust the 201Tl dose according to the patient's body mass index (BMI), with 74 MBq for BMI ≥ 25 and 50 MBq for BMI < 25 (8, 9). In the SDI protocol, the effective dose of isotopes is less than 9 mSv per examination when 50 MBq of 201Tl is administered, but the radiation exposure dose exceeds 9 mSv when 74 MBq of 201Tl is administered. In this study, optimization of 201Tl dosage was investigated to further reduce the radiation exposure dose.
Methods
Patient population
The study included 280 consecutive patients who had undergone stress MPS using the SDI protocol between December 29th, 2021 and February 15th, 2023 to evaluate ischemic heart disease, and were classified into two groups: 201Tl 50 MBq group (n=154) with BMI < 25 and 201Tl 74 MBq group (n=126) with BMI ≥ 25. Patients with a history of prior myocardial infarction were excluded.
Stress MPS protocol
The SDI protocol reported by Makita et al is as follows (8), initially, 125 MBq of 99mTc-Tetrofosmin (Nihon Medi-Physics, Tokyo, Japan) or 99mTc-methoxy isobutyl isonitrile (MIBI; PDRadio pharma, Tokyo, Japan) was injected to visualize resting myocardial perfusion. Then, patients underwent a 6-minute vasodilator stress using an adenosine infusion (120 μg/kg/min; PDRadio pharma Tokyo, Japan). At 3 min after the start of the adenosine infusion, 50-74 MBq of 201Tl was injected to visualize stress myocardial perfusion; patients with BMI > 25 received 74 MBq of 201Tl and those with BMI < 25 received 50 MBq of 201Tl. After the end of loading, 100 ml of carbonated water is ingested before the first acquisition to eliminate the effect of extracardiac tracer accumulation (10). Subsequently, the first simultaneous rest 99mTc/stress 201Tl acquisition performed using D-SPECT in an upright position. After a meal break for about 60 minutes, a second simultaneous rest 99mTc/redistribution 201Tl acquisition of the SDI protocol was performed in an upright position. When imaging with D-SPECT, the patient seats in an upright position and the semiconductor detector is placed as close to the chest wall as possible to obtain sufficient photon counts. the semiconductor detector is placed parallel to the backrest, but the angle is adjusted if it could not be parallel due to obesity or breasts. The first and second acquisition were performed with electrocardiogram (ECG)-gated imaging. Both stress and rest ECG-gated images are taken with 201Tl and 99mTc agents, respectively, but since ECG-gated parameters are more appropriate for measurement with 99mTc images, stress 99mTc (1st acquisition) and rest 99mTc (2nd acquisition) are used for quantitative gated SPECT (QGS) evaluation.
The acquisition time was determined by the number of gamma-ray counts of left ventricle, with a target left ventricular count of 1.0 M count. The manufacturer's recommended left ventricular photon count is 0.5 M counts or higher, but the target count value was set at 1M counts or higher to account for errors.
Statistical analysis
Statistical analysis was performed using EZ-R to determine the correlation between BMI and first acquisition time (min) for the 201Tl 50 MBq or 74 MBq groups (11). Linear regression analysis was used to determine the slope and intercept to derive a linear functional equation to determine the theoretical optimal dose of 201Tl.
Results
Patient characteristics
Patient background characteristics is shown in Table 1, with 154 patients in the 201Tl 50 MBq group and 126 patients in the 201Tl 74 MBq group. 201Tl 50 MBq group was significantly older and BMI and total effective dose (201Tl + 99mTc agent) were significantly lower compared to 201Tl 74 MBq group (age: 73 [64, 80] vs 68 [58.25, 89], p< 0.001, BMI: 22.59 [20.26, 23.795] vs 28.16 [26.76, 30.80], p<0.001, total effective dose: 8.25 [8.15, 8.36] vs 11.97 [11.86, 12.08], P<0.001).
Relationship between BMI and acquisition time
The regression coefficient between BMI and acquisition time for each dose of 201Tl is shown in Figure 1. The regression coefficient for the 201Tl 50 MBq dose group was 0.532 (P<0.00001) and for the 201Tl 74 MBq dose group was 0.478 (P<0.00001), both showing positive correlation. Linear regression analysis revealed two equations: y=0.52x-0.32 (201Tl 50 MBq group) and y=0.41x-0.69 (201Tl 74 MBq group) (Figure 2). Patients with a BMI between 25 and 30 who had previously received 74 MBq of 201Tl could theoretically be tested within approximately 15 minutes with a 50 MBq dose.
Discussion
Although the advent of cadmium zinc telluride gamma cameras has made it possible to shorten acquisition time, the typical acquisition time with conventional anger-type cameras is 15 minutes (12). Considering examination efficiency and patients’ throughput, the ideal acquisition time is less than 15 minutes. Theoretically, patients with BMI less than 30 could be examined within approximately 15 minutes with a 201Tl 50 MBq dose, and the dose could be further reduced for emaciated patients with BMI less than 20.
Patients with BMI<30 accounted for 86.4% of the total, and if these patients could be tested with 50 MBq of 201Tl, it would reduce the exposure of most patients undergoing examination to less than 9 mSv. There were 33 patients with BMI <20, 11.8% of the total. For these patients, a further reduction of the dose of 201Tl was considered possible.
The use of 201Tl is avoided worldwide due to its high radiation dose. However, 201Tl is superior to 99mTc tracers in its higher extraction fraction and in its ability to assess viability through redistribution phenomenon. Higher extraction fraction of 201Tl may increase the chance of ischemic myocardium detection and reduces the risk of missing ischemic myocardium. In addition, severely reduced perfusion defect observed in 99mTc imaging is likely to determine non-viable tissue. However, 201Tl can evaluate viable myocardium properly by its redistribution property. The high photon count sensitivity of dedicated cardiac semiconductor gamma cameras (D-SPECT and Discovery NM 530c) has achieved the optimized radiation exposure in 201Tl imaging. The present study is a simultaneous dual-isotope MPS D-SPECT, and it is not considered possible to apply the protocol to conventional Anger cameras. Since this study was not conducted with other semiconductor gamma cameras, the adaptation is limited to D-SPECT. However, it is thought that imaging with reduced 201Tl dose and exposure dose is possible with semiconductor gamma camera.
Study limitations
Possible causes of prolonged examination time include, (1) small size of the left ventricle (LV), (2) presence of pericardial effusion, (3) fluid retention due to heart failure, and (4) distance from the collimator to the heart. In this study, there were 11 patients whose acquisition time exceeded 15 minutes with 201Tl 50 MBq. LV sizes were obtained using end-diastolic volume from QGS software. However, the end-diastolic volume of patients whose acquisition time exceeded 15 minutes was not significantly different from that of patients whose acquisition time was less than 15 minutes (66 mL [61, 75] vs. 70 mL [54, 84.75], P=0.565). And there were no patients with pericardial effusion or heart failure among those whose acquisition time exceeded 15 minutes. Patients with high BMI have a longer distance from the body surface to the heart and a similarly longer distance from the collimator. Imaging with D-SPECT is performed in an upright sitting position, with the gamma detector as close to the chest wall as possible to obtain adequate counts. However, patients with high BMI may have a thicker chest wall that deviates from the D-SPECT region of interest. In the current study, we did not examine chest circumference, waist circumference, or the distance from the camera, and we were unable to evaluate the relationship between these factors and imaging time. Men may have a thicker lateral chest due to the development of the broad back muscles, and women may have distance and shielding issues due to the breasts. These multiple factors may affect acquisition time.
In Figure 1, there were two cases in the 50 MBq group in which the imaging time exceeded 18 minutes, and two cases in the 74 MBq group in which the imaging time exceeded 25 minutes. None of the possible causes for the decrease in counts already listed in Limitation were applicable. There were no frequent body motions, and the posture during imaging was uniform. However, the distance and shielding from the gamma camera by the thickness of the chest wall, the broad back muscles, and the breast have not been examined. It is possible that these influences may be involved, and studies in the future that take them into account are considered necessary.
Conclusions
In patients with 25≤BMI<30, even if the dose of 201Tl is reduced to 50 MBq, the acquisition time can theoretically be performed within about 15 minutes, and about 86.4% of all patients can be tested with a radiation exposure dose of 9 mSv or less.
Acknowledgments
None.
Sources of funding
None.
Conflicts of interest
None.
References
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