[Radiological Technology for Targeted Radionuclide Therapy].

Targeted radioisotope therapy (TRT) is a radiotherapy using radioisotope or drug incorporating it and has been used as a treatment for selectively irradiating cancer cells. In recent years, interest in TRT has increased due to improvements in radionuclide production technology, development of new drugs and imaging modalities, and improvements in radiation technology. In order to enhance the effect of TRT, measurement of individual radiation doses to tumor tissue and organs at risk is important using highly quantitative nuclear medicine images. In this paper, we present a review of literature on optimization of TRT, which is a new research area from the perspective of radiation technology.

[Global Trends Survey for Targeted Radionuclide Therapy].

Radionuclide therapy has been used to help manage a range of diseases and has a role of growing importance, with an increasing impact on clinical practice globally. A survey in the field of Radionuclide therapy was conducted by reviewing 4199 science abstracts of main conference (Japanese Society of Radiological Technology, Japanese Society of Nuclear Medicine, Japanese Society of Nuclear Medicine Technology, Society of Nuclear Medicine and Molecular Imaging, European Association of Nuclear Medicine) held in 2016. This survey consisted of research content, modality for evaluation, dosimetry, radionuclide, and researcher's country. There tend to be a lot of studies related to targeted radionuclide therapy more than Japan (4%) in the United States (11%) or Europe (13%). Radiopharmaceuticals still un-approving in Japan were used in some of these studies. And many studies on dosimetry using PET or SPECT imaging were confirmed in the United States (37%) or in Europe (25%) compared with in Japan (14%). This survey has clarified the current status of Japan and global trend in the field of radionuclide therapy.

Voxel-wise correlations between cognition and cerebral blood flow using arterial spin-labeled perfusion MRI in patients with Alzheimer's disease: a cross-sectional study.

BACKGROUND: To analyze voxel-wise correlation between cerebral blood flow (CBF) measured using ASL-MRI and cognition in patients with Alzheimer's disease (AD). METHODS: Forty-one patients diagnosed with AD or mild cognitive impairment due to AD were recruited for this study. CBF images were obtained using ASL-MRI (n = 41) with a post-labeling delay (PLD) of 1.5 and 2.5 s (PLD1.5 and PLD2.5, respectively) using a 3 T scanner, in addition to brain perfusion SPECT with N-isopropyl-4-[I-123]iodoamphetamine (n = 28). Voxel-based analyses were performed for ASL-MRI and SPECT using Mini-Mental State Examination (MMSE) scores as covariates. Differences in CBF between PLD1.5 and PLD2.5 were assessed using a paired t-test with SPM12. RESULTS: Significant positive correlations were observed between MMSE scores and CBF at PLD1.5 in the right posterior cingulate cortex (PCC), and both temporo-parietal association cortexes. At PLD2.5, significant positive correlations were determined for MMSE scores and CBF in the superior parietal lobule and the right temporo-parietal association cortex. SPECT showed significant positive correlations in the PCC and both temporo-parietal association cortexes (right-side dominant). PLD1.5 showed significantly higher CBF than PLD2.5 in the proximal areas of vascular territories of the anterior, middle, and posterior cerebral arteries. CONCLUSIONS: Significant positive correlations in CBF, measured with both ASL-MRI and SPECT, with cognition were found in the PCC and temporo-parietal association cortexes. PLD1.5 and PLD2.5 showed similar correlations with cognition, although the CBF images had significant differences.

Biodistribution and radiation dosimetry of the positron emission tomography probe for AMPA receptor, [11C]K-2, in healthy human subjects.

[11C]K-2, a radiotracer exhibiting high affinity and selectivity for α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), is suitable for the quantification of AMPARs in living human brains and potentially useful in the identification of epileptogenic foci in patients. This study aimed to estimate the radiation doses of [11C]K-2 in various organs and calculate the effective dose after injection of [11C]K-2 in healthy human subjects. Twelve healthy male subjects were registered and divided into two groups (370 or 555 MBq of [11C]K-2), followed by 2 h whole-body scans. We estimated the radiation dose of each organ and then calculated the effective dose for each subject. The highest uptake of [11C]K-2 was observed in the liver, while the brain also showed relatively high uptake. The urinary bladder exhibited the highest radiation dose. The kidneys and liver also showed high radiation doses after [11C]K-2 injections. The effective dose of [11C]K-2 ranged from 5.0 to 5.2 µSv/MBq. Our findings suggest that [11C]K-2 is safe in terms of the radiation dose and adverse effects. The injection of 370-555 MBq (10 to 15 mCi) for PET studies using this radiotracer is applicable in healthy human subjects and enables serial PET scans in a single subject.

Safety and efficacy of peptide receptor radionuclide therapy with 177Lu-DOTA0-Tyr3-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA0-Tyr3-octreotate (177Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. METHODS: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of 177Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. RESULTS: Six Japanese patients (three men and three women; mean age 61.5 years; range 50-70 years) with SRS-positive unresectable NETs were recruited. 177Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%-69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of 177Lu-DOTATATE was 16.8 Gy (range 12.0-21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2-21.5 Gy). Administration of 177Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. CONCLUSION: PRRT with 177Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, 177Lu-DOTA0-Tyr3-octreotate .

Harmonization of standardized uptake values between two scanners, considering repeatability and magnitude of the values in clinical fluorine-18-fluorodeoxyglucose PET settings: a phantom study.

OBJECTIVE: The standardized uptake value (SUV) is a quantitative imaging biomarker which has been used the most widely in the field of PET. Current harmonization strategies commonly include image blurring by application of an additional extent of post-reconstruction Gaussian filtering in the aim of recovery coefficient adjustment. The objective of this study was to harmonize SUVmax and SUVpeak measured by an older PET/computed tomography scanner with a newer scanner without depending on image blurring. MATERIALS AND METHODS: We performed multiple phantom studies using a count-based method, in which SUVs can be calculated in a repeatable manner. We measured SUVmax and SUVpeak for spheres of various sizes (10, 13, 18, 22, 28, and 37-mm diameter) and actual SUVs (2, 4, 8, and 16) under standard clinical settings. The measured SUVs were compared with the actual SUVs, and the approximate equations were obtained. The relationships of the equations between two different PET/computed tomography scanners, Aquiduo and Celesteion, were examined to obtain conversion equations. RESULTS: The SUVmax and SUVpeak measured by Aquiduo were lower than those measured by Celesteion. For both scanners, the relationships between the actual and measured SUVs were linearly fit (R>0.99) for each sphere size. The equations varied depending on the sphere size. Also, for large spheres (>2 cm), SUVmax and SUVpeak could be harmonized by simple multiplication, regarding the small absolute values of y-intercept (<0.2) as negligible. CONCLUSION: Size-specific equations to convert SUVmax and SUVpeak measured by Aquiduo into the estimated values on Celesteion were obtained. Also, for large lesions (>2 cm), SUVs may be converted by simple multiplication. These methods might enable simple SUV harmonization which is not based on post-reconstruction Gaussian filtering.

Multicentre analysis of PET SUV using vendor-neutral software: the Japanese Harmonization Technology (J-Hart) study.

BACKGROUND: Recent developments in hardware and software for PET technologies have resulted in wide variations in basic performance. Multicentre studies require a standard imaging protocol and SUV harmonization to reduce inter- and intra-scanner variability in the SUV. The Japanese standardised uptake value (SUV) Harmonization Technology (J-Hart) study aimed to determine the applicability of vendor-neutral software on the SUV derived from positron emission tomography (PET) images. The effects of SUV harmonization were evaluated based on the reproducibility of several scanners and the repeatability of an individual scanner. Images were acquired from 12 PET scanners at nine institutions. PET images were acquired over a period of 30 min from a National Electrical Manufacturers Association (NEMA) International Electrotechnical Commission (IEC) body phantom containing six spheres of different diameters and an 18F solution with a background activity of 2.65 kBq/mL and a sphere-to-background ratio of 4. The images were reconstructed to determine parameters for harmonization and to evaluate reproducibility. PET images with 2-min acquisition × 15 contiguous frames were reconstructed to evaluate repeatability. Various Gaussian filters (GFs) with full-width at half maximum (FWHM) values ranging from 1 to 15 mm in 1-mm increments were also applied using vendor-neutral software. The SUVmax of spheres was compared with the reference range proposed by the Japanese Society of Nuclear Medicine (JSNM) and the digital reference object (DRO) of the NEMA phantom. The coefficient of variation (CV) of the SUVmax determined using 12 PET scanners (CVrepro) was measured to evaluate reproducibility. The CV of the SUVmax determined from 15 frames (CVrepeat) per PET scanner was measured to determine repeatability. RESULTS: Three PET scanners did not require an additional GF for harmonization, whereas the other nine required additional FWHM values of GF ranging from 5 to 9 mm. The pre- and post-harmonization CVrepro of six spheres were (means ± SD) 9.45% ± 4.69% (range, 3.83-15.3%) and 6.05% ± 3.61% (range, 2.30-10.7%), respectively. Harmonization significantly improved reproducibility of PET SUVmax (P = 0.0055). The pre- and post-harmonization CVrepeat of nine scanners were (means ± SD) 6.59% ± 1.29% (range, 5.00-8.98%) and 4.88% ± 1.64% (range, 2.65-6.72%), respectively. Harmonization also significantly improved the repeatability of PET SUVmax (P < 0.0001). CONCLUSIONS: Harmonizing SUV using vendor-neutral software produced SUVmax for 12 scanners that fell within the JSNM reference range of a NEMA body phantom and improved SUVmax reproducibility and repeatability.

Use of count-based image reconstruction to evaluate the variability and repeatability of measured standardised uptake values.

Standardized uptake values (SUVs) are the most widely used quantitative imaging biomarkers in PET. It is important to evaluate the variability and repeatability of measured SUVs. Phantom studies seem to be essential for this purpose; however, repetitive phantom scanning is not recommended due to the decay of radioactivity. In this study, we performed count-based image reconstruction to avoid the influence of decay using two different PET/CT scanners. By adjusting the ratio of 18F-fluorodeoxyglucose solution to tap water, a NEMA IEC body phantom was set for SUVs of 4.0 inside six hot spheres. The PET data were obtained using two scanners (Aquiduo and Celesteion; Toshiba Medical Systems, Tochigi, Japan). We set the start time for image reconstruction when the total radioactivity in the phantom was 2.53 kBq/cc, and employed the counts of the first 2-min acquisition as the standard. To maintain the number of counts for each image, we set the acquisition time for image reconstruction depending on the decay of radioactivity. We obtained 50 images, and calculated the SUVmax and SUVpeak of all six spheres in each image. The average values of the SUVmax were used to calculate the recovery coefficients to compare those measured by the two different scanners. Bland-Altman analyses of the SUVs measured by the two scanners were also performed. The measured SUVs using the two scanners exhibited a 10-30% difference, and the standard deviation (SD) of the measured SUVs was between 0.1-0.2. The Celesteion always exhibited higher values than the Aquiduo. The smaller sphere exhibited a larger SD, and the SUVpeak had a smaller SD than the SUVmax. The Bland-Altman analyses showed poor agreement between the SUVs measured by the two scanners. The recovery coefficient curves obtained from the two scanners were considerably different. The Celesteion exhibited higher recovery coefficients than the Aquiduo, especially at approximately 20-mm-diameter. Additionally, the curves were lower than those calculated from the standard 30-min acquisition images. We propound count-based image reconstruction to evaluate the variability and repeatability of measured SUVs. These results are also applicable for the standardization and harmonization of SUVs in multi-institutional studies.

Initial evaluation of the Celesteion large-bore PET/CT scanner in accordance with the NEMA NU2-2012 standard and the Japanese guideline for oncology FDG PET/CT data acquisition protocol version 2.0.

BACKGROUND: The goal of this study was to evaluate the performance of the Celesteion positron emission tomography/computed tomography (PET/CT) scanner, which is characterized by a large-bore and time-of-flight (TOF) function, in accordance with the NEMA NU-2 2012 standard and version 2.0 of the Japanese guideline for oncology fluorodeoxyglucose PET/CT data acquisition protocol. Spatial resolution, sensitivity, count rate characteristic, scatter fraction, energy resolution, TOF timing resolution, and image quality were evaluated according to the NEMA NU-2 2012 standard. Phantom experiments were performed using 18F-solution and an IEC body phantom of the type described in the NEMA NU-2 2012 standard. The minimum scanning time required for the detection of a 10-mm hot sphere with a 4:1 target-to-background ratio, the phantom noise equivalent count (NECphantom), % background variability (N 10mm), % contrast (Q H,10mm), and recovery coefficient (RC) were calculated according to the Japanese guideline. RESULTS: The measured spatial resolution ranged from 4.5- to 5-mm full width at half maximum (FWHM). The sensitivity and scatter fraction were 3.8 cps/kBq and 37.3%, respectively. The peak noise-equivalent count rate was 70 kcps in the presence of 29.6 kBq mL-1 in the phantom. The system energy resolution was 12.4% and the TOF timing resolution was 411 ps at FWHM. Minimum scanning times of 2, 7, 6, and 2 min per bed position, respectively, are recommended for visual score, noise-equivalent count (NEC)phantom, N 10mm, and the Q H,10mm to N 10mm ratio (QNR) by the Japanese guideline. The RC of a 10-mm-diameter sphere was 0.49, which exceeded the minimum recommended value. CONCLUSIONS: The Celesteion large-bore PET/CT system had low sensitivity and NEC, but good spatial and time resolution when compared to other PET/CT scanners. The QNR met the recommended values of the Japanese guideline even at 2 min. The Celesteion is therefore thought to provide acceptable image quality with 2 min/bed position acquisition, which is the most common scan protocol in Japan.

Variation and repeatability of measured standardized uptake values depending on actual values: a phantom study.

Standardized uptake values (SUVs) are the most widely used quantitative imaging biomarkers in positron emission tomography (PET); however, little is known about the changes in variation and repeatability of SUVs depending on the magnitude of the values. We hypothesized that low SUVs have larger variations than high SUVs, and attempted various kinds of experimental PET scans using a phantom. By adjusting the ratio of F-18 solution to tap water, a NEMA IEC body phantom was set for SUVs of 2.0, 4.0, and 8.0 inside six hot spheres. PET data were obtained for 4 hours, and the data reconstructed every 2 min. The SUVmax and SUVpeak of the spheres in all images were recorded. The relative SUVs were calculated by dividing the measured SUV by actual SUV, and used for the Bland-Altman plots. Some variation was observed for the measured SUVs. The measured SUVs for the actual SUV of 2.0 showed the largest variation among those of 2.0, 4.0, and 8.0, and those of 8.0 showed the smallest. Similarly, the relative SUVs showed significantly larger variations for lower values. In addition, the relative SUVmax showed larger variation and value than the relative SUVpeak. The Bland-Altman plots showed considerable variation and little agreement, but the degree of variation decreased as the measured value increased. We demonstrated some variation of the measured SUVs, which decreased for larger measured values. Clinicians should consider the inaccuracy of low SUVs not only in daily practice, but also for multi-institutional studies.

Regional cerebral glucose metabolism in systemic lupus erythematosus patients with major depressive disorder.

OBJECTIVES: Depression is frequently observed in patients with systemic lupus erythematosus (SLE). Neuropsychiatric SLE (NPSLE) patients often exhibit cerebral hypometabolism, but the association between cerebral metabolism and depression remains unclear. To elucidate the features of cerebral metabolism in SLE patients with depression, we performed brain 18F-fluoro-d-glucose positron emission tomography (FDG-PET) on SLE patients with and without major depressive disorder. METHODS: We performed brain FDG-PET on 20 SLE subjects (5 male, 15 female). The subjects were divided into two groups: subjects with major depressive disorder (DSLE) and subjects without major depressive disorder (non-DSLE). Cerebral glucose metabolism was analyzed using the three-dimensional stereotactic surface projection (3D-SSP) program. Regional metabolism was evaluated by stereotactic extraction estimation (SEE), in which the whole brain was divided into segments. RESULTS: Every SLE subject exhibited cerebral hypometabolism, in contrast to the normal healthy subjects. Regional analysis revealed a significantly lower ER in the left medial frontal gyrus (p=0.0055) and the right medial frontal gyrus (p=0.0022) in the DSLE group than in the non-DSLE group. CONCLUSION: Hypometabolism in the medial frontal gyrus may be related to major depressive disorder in SLE. Larger studies are needed to clarify this relationship.

Differences in sodium fluoride-18 uptake in the normal skeleton depending on the location and characteristics of the bone.

AIM: The aim of this study was to evaluate the normal distribution of sodium fluoride-18 (NaF-18) and to clarify the differences in uptake according to location and the type of the bone using positron emission tomography (PET) / computed tomography (CT). METHODS: We retrospectively reviewed NaF-18 PET/CT images from 30 patients with hip joint disorders. PET/CT scans were performed 40 min after injection of approximately 185 MBq of NaF-18. To evaluate the relationship between the distribution of NaF-18 uptake and bone density, we compared the maximum standardised uptake values (SUVmax) on PET and the Hounsfield Units (HUs) on CT of the lumbar vertebra, ilium, and proximal and distal femurs. Regions of interests were defined both outside and inside the cortical bone to measure whole bone and cancellous bone only, respectively. RESULTS: The distribution of NaF-18 differed according to the skeletal site. The lumbar vertebra showed the highest SUVmax for both whole bone and cancellous bone, followed by the ilium, proximal femur, and distal femur. The bones differed significantly in SUVmax. The distal femur showed the highest HU, followed by the proximal femur, ilium, and vertebra. Profile curve analyses demonstrated that the cancellous bones showed higher SUVmax and lower HU than the cortical bones. CONCLUSIONS: Our results demonstrate the difference in NaF-18 uptake between cancellous and cortical bones, which may explain differences in uptake by location. NaF-18 uptake does not appear to be strongly correlated with bone density, but rather with bone turnover and blood flow.

SUV measurement of normal vertebrae using SPECT/CT with Tc-99m methylene diphosphonate.

The purpose of this study is to perform quantitative measurement based on the standardized uptake value (SUV) of the uptake of Tc-99m methylene diphosphonate (MDP) in the normal vertebrae using a single photon emission tomography (SPECT)/computed tomography (CT) scanner. A retrospective study of patients with cancer or joint disorders was performed. We acquired data for a group of 29 patients (8 women and 21 men; mean age, 68.2 ± 6.7 years; age range, 44-87 years) undergoing bone SPECT/CT scans with Tc-99m MDP between September and October 2015. Various SUVs were calculated based on body-weight, lean-body-weight (lbw), Japanese lean-body-weight (jlbw) and Japanese bone-mineral-content (jbmc). SUVs of normal vertebrae showed a wide range of values. Among these, the maximum body-weight based SUV showed the lowest coefficient of variation. The SUVs also showed relatively small intra-subject variability. In addition, all SUVs showed moderate and significant correlation with height. Moreover, lbw-, jlbw-, and jbmc-based SUVs of men were significantly higher than those of women. In conclusions, SUVs of normal vertebrae showed a relatively large inter-individual variability and small intra-individual variability. As a quantitative imaging biomarker, SUVs might require standardization with adequate reference data for the same subject to minimize variability.