A first-in-man study of [18F] FEDAC: a novel PET tracer for the 18-kDa translocator protein.

PURPOSE: N-benzyl-N-methyl-2-[7, 8-dihydro-7-(2-[18F] fluoroethyl) -8-oxo-2-phenyl-9H-purin-9-yl] acetamide ([18F] FEDAC) is a novel positron emission tomography (PET) tracer that targets the translocator protein (TSPO; 18 kDa) in the mitochondrial outer membrane, which is known to be upregulated in various diseases such as malignant tumors, neurodegenerative diseases, and neuroinflammation. This study presents the first attempt to use [18F]FEDAC PET/CT and evaluate its biodistribution as well as the systemic radiation exposure to the radiotracer in humans. MATERIALS AND METHODS: Seventeen whole-body [18F]FEDAC PET/CT (injected dose, 209.1 ± 6.2 MBq) scans with a dynamic scan of the upper abdomen were performed in seven participants. Volumes of interest were assigned to each organ, and a time-activity curve was created to evaluate the biodistribution of the radiotracer. The effective dose was calculated using IDAC-Dose 2.1. RESULTS: Immediately after the intravenous injection, the radiotracer accumulated significantly in the liver and was subsequently excreted into the gastrointestinal tract through the biliary tract. It also showed high levels of accumulation in the kidneys, but showed minimal migration to the urinary bladder. Thus, the liver was the principal organ that eliminated [18F] FEDAC. Accumulation in the normal brain tissue was minimal. The effective dose estimated from biodistribution in humans was 19.47 ± 1.08 µSv/MBq, and was 3.60 mSV for 185 MBq dose. CONCLUSION: [18F]FEDAC PET/CT provided adequate image quality at an acceptable effective dose with no adverse effects. Therefore, [18F]FEDAC may be useful in human TSPO-PET imaging.

Biokinetic model analysis with DTPA administration for a case of accidental inhalation of actinides in Japan.

Accidental inhalation intake of plutonium isotopes and 241Am occurred at a Pu research facility in Japan in 2017, and the five workers involved in this accident were treated by the administration of Ca/Zn-diethylenetriaminepentaacetic acid (DTPA). For the worker who was most internally exposed, the therapy was continued over 1 y after the accident. Urinary samples collected before and after each administration were subject to bioassay to evaluate the efficacy of the dose reduction. This study performed numerical analyses using a biokinetic model dealing with 241Am-DTPA with reference to the European Coordinated Network on Radiation Dosimetry approach, which assumes that the complex of actinides and Ca/Zn-DTPA is generated in the designated compartments in the biokinetic model. The results of the model prediction well captured the trend of the observed urinary excretion in the long-term bioassay and would be useful to evaluate the efficacy of the Ca/Zn-DTPA administration for the worker involved in the accident.

Reassessment of Internal Thyroid Doses to 1,080 Children Examined in a Screening Survey after the 2011 Fukushima Nuclear Disaster.

The dose reconstruction of populations potentially affected by the accident at the Fukushima Daiichi nuclear power plant in March 2011 is of great importance. However, it has been difficult to assess internal thyroid doses to Fukushima residents (mainly from their intake of I) due to the lack of direct measurements. For the residents, only about 1,300 data points related to I are available, and 1,080 of the data points were obtained from the screening campaign that was conducted by the Nuclear Emergency Response Local Headquarters at the end of March 2011 in Kawamata Town, Iwaki City, and Iitate Village. Here, we reassessed thyroid doses to 1,080 subjects aged ≤15 y old using new age-specific conversion factors to determine I thyroid contents from net signals of the devices used, with consideration for the possible uncertainty related to the measurements. The results demonstrated that thyroid equivalent doses to the subjects were <30 mSv (excluding outliers). We also demonstrate dose distributions of each age group from the above three municipalities and those of subjects from Minamisoma City and Fukushima City. One of the findings was that the I intake was similar among different age groups in each of the three municipalities. This was consistent with the assumption that ingestion was a dominant route of intake rather than inhalation. The range of thyroid doses to Iitate Village residents was similar to that to Iwaki City residents even though the I concentration in tap water was much higher in Iitate Village than Iwaki City. The range of thyroid doses to Minamisoma City residents was similar to that to Iitate Village and Iwaki City residents, and the range for Fukushima City residents was smallest among the five municipalities. Since the major route of intake has remained unclear, this paper presents the plausible upper and lower thyroid doses, between which the actual doses are thought to mostly exist, based on two intake scenarios: single inhalation and repeated ingestion. Further research is thus necessary to extract useful evidence from the individual evacuation behaviors for improving the present internal thyroid dose assessment.

NUMERICAL SIMULATION OF DIRECT MEASUREMENT TO DETERMINE THYROID 131I CONTENT OF TWO TEPCO WORKERS CONSIDERING INDIVIDUAL TISSUE THICKNESS.

After the Fukushima Daiichi Nuclear Power Station accident, the National Institute of Radiological Sciences examined seven heavily exposed emergency workers and performed internal dose estimations. The largest dose contributor was found to be (131)I, which was detected by thyroid monitor with an HPGe detector. Different energy peaks from (131)I were simultaneously identified in the pulse-height spectra of the two subjects with the highest doses regardless of late measurements. A closer look at the spectra indicated that the count ratio of the two peak areas at 80.2 and 365 keV differed somewhat between the individual workers, suggesting a difference in attenuation in the overlaying soft tissue and in the thyroid itself. In this study, the relationship between the count ratio (80.2/365 keV) and the thickness of soft tissue overlying the thyroid was investigated by means of numerical simulations performed using the Japanese Male (JM) phantom varying the thickness of the overlaying tissue. From the measured count ratios, it was possible to estimate that the overlaying tissue was thinner for Worker 1 (difference from the JM phantom: -0.34±1.29 cm) and thicker for Worker 2 (diff.: 2.5±1.2 cm). The thyroid (131)I contents evaluated taking into account the individual thicknesses were 4.3 kBq for Worker 1 and 8.4 kBq for Worker 2, resulting in a significant increase for Worker 2 compared with the content based on the default counting efficiency at 365 keV of the original JM phantom. However, the results have large uncertainty factors of 1.4 for Worker 1 and 1.3 for Worker 2 and should be carefully considered together with other factors influencing the attenuation.

Skull counting in late stages after internal contamination by actinides.

Monitoring preparation for internal contamination with actinides (e.g. Pu and Am) is required to assess internal doses at nuclear fuel cycle-related facilities. In this paper, the authors focus on skull counting in case of single-incident inhalation of (241)Am and propose an effective procedure for skull counting with an existing system, taking into account the biokinetic behaviour of (241)Am in the human body. The predicted response of the system to skull counting under a certain counting geometry was found to be only ∼1.0 × 10(-5) cps Bq(-1) 1y after intake. However, this disadvantage could be remedied by repeated measurements of the skull during the late stage of the intake due to the predicted response reaching a plateau at about the 1000th day after exposure and exceeding that in the lung counting. Further studies are needed for the development of a new detection system with higher sensitivity to perform reliable internal dose estimations based on direct measurements.

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging.

OBJECTIVES: Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of <1 mm, but few studies have focused on the evaluation of intratumoral heterogeneity. We investigated the optimal conditions related to high resolution imaging of heterogeneous tumor interiors using a small animal SPECT scanner. METHODS: The conditions related to SPECT/CT visualization of heterogeneous tumor interiors were investigated using phantoms with (111)In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice. RESULTS: Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30 min, better image quality was obtained with pinhole apertures diameter of 1.4 mm than of 1.0 mm. The obtained best spatial resolution was 1.3 mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0 mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2-0.5 MBq/mL. Liposomes containing (111)In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous (111)In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2 MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes. CONCLUSION: Intratumoral heterogeneity was successfully visualized under the optimized conditions using a SPECT/CT scanner.