Relationship between [18F]FDG PET/CT and metabolomics in patients with colorectal cancer.

INTRODUCTION: Advances in metabolomics have significantly improved cancer detection, diagnosis, treatment, and prognosis. OBJECTIVES: To investigate the relationship between metabolic tumor volume (MTV) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/ computed tomography (CT) and metabolomics data in patients with colorectal cancer (CRC). METHODS: The metabolome in tumor tissues was analyzed using capillary electrophoresis time-of-flight mass spectrometry in 33 patients with newly diagnosed CRC who underwent FDG PET/CT before treatment and had tumor tissue post-surgery. Based on the FDG PET data, MTV was calculated and was dichotomized according to the median value, and tumors were divided into low-MTV and high-MTV tumors. Metabolomics data were compared between the low-MTV and high-MTV tumors. RESULTS: The levels of most glycolysis-related metabolites were not different between low-MTV and high-MTV tumors. The level of component of the initial part of the tricarboxylic acid (TCA) cycle, citrate, was significantly lower in the high-MTV tumor than in the low-MTV tumor. The TCA intermediate succinate level was significantly higher in the high-MTV tumor than in the low-MTV tumor. In contrast, the TCA intermediate fumarate level was significantly lower in the high-MTV tumor than in the low-MTV tumor. The levels of many amino acids were significantly higher in the high-MTV tumor than in the low-MTV tumor. CONCLUSIONS: Although preliminary, these results suggest that tumors with high FDG metabolism in CRC may obtain more energy by using a reverse reaction of the TCA cycle and amino-acid metabolism. However, further research is required to clarify this relationship.

[Investigation of Radioactivity Concentration of the Normal Brain Region for the Phantom Experiment in Brain Tumor PET Imaging].

PURPOSE: There are few reports focusing on the radioactivity concentration in the normal brain region for the phantom experiment. We investigated the radioactivity concentration of normal brain regions for the phantom experiment of brain tumor PET imaging. METHODS: A total of 30 patients (age: 53±19 years old, body weight: 58±11 kg) underwent the brain tumor PET examinations using 18F-fluorothymidine (18F-FLT), 18F-fluoromisonidazole (18F-FMISO) and 11C-methionine (11C-MET) during April 1, 2017-October 1, 2017. A region of interest was set in the brain parenchyma excluding the tumor lesion area and the ventricle in PET image, and radioactivity concentrations of the normal brain region were obtained. RESULTS: The radioactivity concentrations of the normal brain region were 0.79±0.25 kBq/ml for 18F-FLT, 2.34±0.42 kBq/ml for 18F-FMISO and 4.05±0.80 kBq/ml for 11C-MET. CONCLUSION: We proposed the radioactivity concentrations of background region in the phantom for brain tumor PET imaging using 18F-FLT, 18F-FMISO and 11C-MET.

[Investigation of Computed Tomography Exposure Dose for Whole-body 18F-FDG PET/CT Examination in Chugoku-Shikoku Regions].

PURPOSE: We investigated the way of thinking about the CT dose setting, the exposure dose (CTDIvol, DLP) and the image quality (standard deviation of liver: SDliver) of whole-body PET/CT examinations in the Chugoku and Shikoku regions for the optimized CT dose setting. METHOD: It was researched in the target 29 facilities which is equipped with 18F-FDG, PET/CT scanner in that regions. We examined how to determine the dose of complete physical PET/CT setting, the CT radiation dose (CTDIvol and DLP) and the image quality of CT fusion image that is the standard deviation of liver CT value in each facility. RESULT: The optimized CT dose was lower than the diagnostic CT in many facilities. The 75th percentile CTDIvol was 6.01 mGy. The 75th percentile DLP was 560.9 mGy ×cm. The SDliver was 14.6±5.3 HU. CONCLUSION: The CT condition was low setting in comparison with diagnostic CT in many facilities. The exposure dose was lower than the diagnostic CT dose. The image quality of the normal region of liver was very close to the diagnostic CT. Even though it was low dose, images were less noise components.

[Evaluation of Measurement Accuracy and Inter-institutional Comparison for Dose Calibrators].

PURPOSE: The aim of this study was to validate the reliability of dose calibrators for measuring the radioactivity of several radioisotopes in multi-institution. METHODS: We evaluated the measurement accuracy of dose calibrators using a commercially available source ((67) Ga, (99m) Tc, (123) I, (201) TL). Nine dose calibrators (five models) in seven institutions were performed in this study. Each source was measured at least 3 times a day over a period of 4 half-life. Linearity of concentration (%error value) and percent difference values (%diff measurement) between measured and estimated radioactivity were calculated to evaluate the measurement accuracy. In addition, difference among institutions (%diff institution) was evaluated by the error values between measured and reference institution values. RESULTS: Good linearity of concentration was found between measured and estimated radioactivity in (99m)Tc and (123)I. However, %error value was increased in (67)Ga and (201)TL (maximum 19.3%). %diff measurements were 1.9 ± 0.3% for (67)Ga, -0.9 ± 0.3% for (99m)Tc, 2.2 ± 0.4% for (123)I, and -0.7 ± 0.3% for (201)TL, respectively. Although there were no clear differences in six institutions, %diff institution in one institution tended to be higher than that obtained in other institutions. CONCLUSIONS: Our results indicated that measurement accuracy of nine dose calibrators (five models) was relatively stable. However, difference of measured values tended to be higher in a part of institution and source. It is important to perform quality assurance and quality control for dose calibrator using traceable source.

[Evaluation of Resolution Correction in Single Photon Emission Computed Tomography Reconstruction Method Using a Body Phantom: Study of Three Different Models].

PURPOSE: The aim of this study was to evaluate the resolution recovery techniques of Flash3D, Astonish, and Evolution in single photon emission computed tomography(SPECT) using a body phantom. METHODS: We scanned a National Electrical Manufactures Association body phantom filled with 99mTc. The body of the phantom with radioactive sphere and background was filled with either water or radioactive solution. We investigated image quality using profile curves, recovery coefficient, and image contrast. RESULTS: The profile curve at the edge of the hot sphere showed artifact due to Gibbs oscillation for all techniques, and also over estimation of recovery coefficient was seen in the hot sphere, as had been previously reported in a simulation study. These phenomena were more remarkable than Evolution in the Flash3D and Astonish techniques. For the contrast between hot sphere and background, the contrast recover was enough for the <17-mm hot spheres. These results showed that the effect of contrast correction was less as the radius of rotation diameter became large. CONCLUSION: In the present study using the body phantom, overestimated counts and edge artifacts due to Gibbs oscillation were shown. These phenomena were different by each resolution correction algorithms. Also, there were limitation regarding image quality improvement by resolution correction depending on sphere size and length of radius of rotation.

Correlation between ¹8F-fluoromisonidazole PET and expression of HIF-1α and VEGF in newly diagnosed and recurrent malignant gliomas.

PURPOSE: Hypoxia and its consequences at the molecular level promote tumour progression and affect patient prognosis. One of the main early cellular events evoked by hypoxia is induction of hypoxia-inducible factor 1 (HIF-1) and subsequent upregulation of vascular endothelial growth factor (VEGF). In this study we sought to determine whether hypoxia detected by (18)F-fluoromisonidazole (FMISO) PET accurately reflects the expression of HIF-1α and VEGF in the tumour and can be used as a biomarker of antiangiogenic treatment and as a prognostic factor in newly diagnosed and recurrent malignant gliomas. METHODS: Enrolled in this study were 32 patients with newly diagnosed glioma and 16 with recurrent glioma of grade III or grade IV. All the patients had undergone FMISO PET preoperatively. The maximum tumour-to-blood FMISO activity ratio (T/Bmax) was used to evaluate the degree of tumour hypoxia and the hypoxic volume (HV) was calculated using a tumour-to-blood FMISO uptake ratio of ≥1.2. Immunohistochemical expressions of HIF-1α and VEGF were evaluated semiquantitatively using the immunoreactivity score (IRS, scores 0 to 12) and the correlation was examined between IRS of HIF-1α or VEGF and FMISO uptake of the tumour (SUVtumour) using navigation-based sampling. Survival was estimated using the Kaplan-Meier method in relation to the T/Bmax and the HV. RESULTS: The T/Bmax and the HV in grade IV gliomas were significantly higher than in grade III gliomas (P < 0.01 and P < 0.01, respectively). Moderate to strong HIF-1α and VEGF expression was observed in the majority of malignant gliomas. The IRS of HIF-1α and VEGF in the tumour were not significantly different between grade III and grade IV gliomas. The IRS of HIF-1α in the tumour did not correlate with the SUVtumour of FMISO in either newly diagnosed or recurrent glioma. There was a significant but weak correlation between the IRS of VEGF and the SUVtumour of FMISO in newly diagnosed glioma, but not in recurrent glioma. The overall survival time in patients with a small HV and a low FMISO T/Bmax was significantly longer than in those with a large HV and a high FMISO T/Bmax (P < 0.01 and P < 0.05, respectively). CONCLUSION: Preoperative FMISO uptake is significantly correlated with the expression of VEGF in the tumour and might be used as a biomarker of antiangiogenic treatment in newly diagnosed malignant gliomas. However, caution is required because the correlation was weak and there was a large overlap of FMISO uptake between glioma with high and low VEGF expression. In addition, hypoxia determined by FMISO PET appears to be a suitable biomarker for predicting a highly malignant tumour and a poor prognosis in patients with malignant glioma.

[Accuracy of Injection Dose of Amyloid PET Agent Using Radiopharmaceutical Activity Suppliers].

PURPOSE: This study aimed to identify disposable items with low amyloid positron emission tomography (PET) agent radioactivity adsorption for accurate injections using a radiopharmaceutical activity supplier. METHODS: First, we investigated disposable items currently used for amyloid PET agent injection. Next, we measured the residual radioactivity rates of amyloid PET agents on three-way stopcocks, extension tubes, butterfly needles, and indwelling needles to identify disposable items with low radioactivity adsorption. Finally, we evaluated the accuracy of amyloid PET agent injection using the selected disposable items and a radiopharmaceutical activity supplier. RESULTS: The polybutadiene extension tube exhibited a significantly lower residual activity rate than that of the polyvinyl chloride extension tube. Similarly, the indwelling needles showed significantly lower residual activity rate than that of butterfly needles. The dose indicated by a radiopharmaceutical activity supplier was 184.1 MBq, while the dose calibrator measured the radioactivity which flowed into the vial as 170.2 MBq, resulting in an administration accuracy of 8.2%. CONCLUSION: To ensure accurate amyloid PET agent injections, we recommend using polybutadiene extension tubes and indwelling needles due to their lower radioactivity adsorption.

Administered dosage and effective dose estimated from 81Rb-rubidium hydroxide for lung ventilation scintigraphy using 81mKr noble gas.

The aim of this study was to estimate the administered dosage of 81mKr noble gas as calculated by the radioactivity of 81Rb-rubidium hydroxide (81RbOH). The administered dosage was regarded as the total amount of 81mKr noble gas. The radioactivity of 81mKr was calculated using the radioactivity of 81RbOH at the examination, the beginning of inhalation, the inhalation duration and the attenuation volume from the generator to the patient for 81mKr noble gas. In addition, we created an Internet survey and asked National University Hospital in Japan to respond to questions regarding the parameters of concern. Survey responses were provided by 38 hospitals (response rate was 90.5%). Twenty-seven hospitals (64.3%) examined lung ventilation scintigraphy using 81mKr noble gas. The mean administered dosage and the effective dose of lung ventilation scintigraphy using 81mKr noble gas were 35.8 ± 22.1 GBq and 0.97 ± 0.60 mSv, respectively.

Physiological myocardial 18F-FDG uptake pattern in oncologic PET/CT: comparison with findings in cardiac sarcoidosis.

Objectives: Physiological myocardial 18F-fluorodeoxyglucose (18F-FDG) uptake in oncologic positron emission tomography (PET)/computed tomography (CT) is commonly observed with multiple variations under clinical fasting conditions. The purpose of the present study was to evaluate physiological myocardial 18F-FDG uptake pattern by comparing with the results in cardiac sarcoidosis. Methods: A total of 174 examinations in 174 patients without cardiac disease and 27 examinations in 17 patients with cardiac sarcoidosis were performed. The polar map images generated from 18F-FDG PET/CT data were visually assessed as "basal-ring," "focal," and "focal on diffuse" patterns. Semi-quantitative analysis was also performed using the regional relative 18F-FDG uptake (% uptake). Results: On visual analysis, the "focal on diffuse" pattern was the most common in both examinations (43% and 59%, respectively). The physiological % uptake in the lateral and basal septal walls tended to be higher. Subgroup analysis showed significantly higher uptake in the mid-wall and left circumflex territory. In cardiac sarcoidosis patients, there was a significant difference only between segments 2 and 15 (p=0.04). No significant differences were observed between the base-mid-apical territory and coronary artery branch territory. Conclusion: High 18F-FDG uptake in the basal septal walls is likely to be observed as both physiological uptake in patients without cardiac disease and pathological uptake in patients with cardiac sarcoidosis.

Nuclear medicine practice in Japan: a report of the ninth nationwide survey in 2022.

Subcommittee on Survey of Nuclear Medicine Practice in Japan has performed a nationwide survey of nuclear medicine practice every 5 years since 1982 to survey contemporary nuclear medicine practice and its changes over the years. The subcommittee sent questionnaires, including the number and category of examinations as well as the kind of the radiopharmaceuticals during the 30 days of June 2022 to all nuclear medicine institutes in Japan. The total numbers of them for the year 2022 were estimated depends on the 1-month data. A total of 1095 institutes responded to the survey, including 364 positron emission tomography (PET) centers. The recovery rate was 90.6%. The number of gamma cameras installed was 1299 in total, with 2.5% decrease in 5 years. Dual-head cameras and hybrid SPECT/CT scanners accounted for 83.8% and 35.5%, respectively. The number of single-photon tracer studies in 2022 was 1.11 million which means increase in 2.7% in 5 years. Bone scintigraphy was a leading examination (31.0%), followed by myocardial scintigraphy (27.1%) and cerebral perfusion study (23.8%) in order. The percentage of SPECT studies showed an increase from 63.5% in previous survey to 66.8% in this survey. PET centers have also increased from 389 to 412, as compared with the previous one. One hundred and twenty-two PET centers have installed one or two in-house cyclotrons. Increasing trends of the PET studies were observed from 1992 to 2017, the trend changed and PET studies showed 1.5% decrease in 5 years. 18F-FDG accounted for 98.6% (610,497 examinations). PET examinations using 11C-methionine, 13N-NH3 and 11C-PIB have decreased, with 1624, 2146 and 525 examinations, respectively in 2022. The total number of nuclear medicine examination was eventually increased by 1.0%. Therapies for pheochromocytoma or paraganglioma (PPGL) with 131I-MIBG and for neuroendocrine tumor with 177Lu-DOTA-TATE were newly started, however, a total number of targeted radionuclide therapy was decreased by 17.7% because 131I-radioiodine and 223Ra targeted therapies were decreased and supply of some radioisotopes was discontinued. 131I-radioiodine targeted therapy showed a decrease in 5 years (- 15.9%), including 4099 patients for thyroid cancer. The number of out-patient thyroid bed ablation therapy with 1110 MBq of 131I was also decreased to 1015 per year. The number of admission rooms specialized for radionuclide targeted therapy increased from 157 to 160. The number of 223Ra targeted therapies for castration-resistant metastatic prostate cancer (mCRPC) was 1041 patients. This survey was performed during COVID-19 pandemic, however, total number of nuclear medicine examinations was almost same as previous survey (+ 1.0%). Radionuclide therapies with 131I-MIBG and 177Lu-DOTA-TATE were newly started, and new radionuclide therapy will be available in future, therefore, the development of radionuclide therapy will be continued. We are convinced that this survey report is useful in understanding the current status of the nuclear medicine practice in Japan, and in devising the new strategy to strengthen a role of nuclear medicine.

Detection of brain amyloid ß deposition in patients with neuropsychological impairment after traumatic brain injury: PET evaluation using Pittsburgh Compound-B.

OBJECTIVE: Traumatic brain injury (TBI) is an epigenetic risk factor for Alzheimer's disease (AD) and amyloid ß (Aß) deposition is observed histopathologically in the traumatized brain. This study was conducted to detect cerebral Aß deposition using amyloid positron emission tomography (PET) in patients with neuropsychological impairment after TBI. METHODS: Twelve patients with post-traumatic neuropsychological impairment (11 men and one woman, age range = 21-78 years) were examined using Pittsburgh Compound B ((11)C-PIB) PET at the chronic stage after TBI (range = 5-129 months). RESULTS: (11)C-PIB was positive in three patients and negative in the other nine patients. There was no correlation between (11)C-PIB deposition and the severity of injury; initial CT findings; elapsed time from the injury; and neuropsychological test scores. CONCLUSIONS: The absence of Aß deposition in many patients with chronic neuropsychological impairment after TBI does not support the premise that Aß pathology progresses over time in the traumatized brain. Early and sequential (11)C-PIB PET examination may clarify the time course of Aß deposition in the traumatized brain and the relationship between traumatic brain insult and subsequent neuropsychological impairment.

Feasibility of whole-body 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography angiography using continuous bed motion in patients with vascular disease: a pilot study.

OBJECTIVE: Positron emission tomography (PET) angiography is a promising PET imaging method for vessel evaluation. With advances in PET technologies, PET angiography of the whole body is now possible using continuous bed motion (CBM) mode. This study aimed to evaluate the image quality for depicting the aorta and main branches and the diagnostic performance of whole-body PET angiography in patients with vascular disease. METHODS: We retrospectively identified 12 consecutive patients who underwent whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET angiography in CBM mode. Whole-body PET angiography was performed between 20 and 45 s after administering [18F]FDG using CBM from the neck to the pelvis. The visibility of whole-body PET angiography was assessed for the 24 segments in three regions per patient using a 4-point grading scale (1, unacceptable; 2, poor; 3, good; 4, excellent), and grades 3 and 4 were considered diagnostic. The diagnostic accuracy of whole-body PET angiography for detecting vascular abnormalities was calculated using contrast-enhanced CT as a reference standard. RESULTS: We evaluated 285 segments from 12 patients, and overall, 170/285 segments (60%) were considered diagnostic throughout the whole body, including 96/117 (82%), 22/72 (31%), and 52/96 (54%) segments in the neck-to-chest region, abdominal region, and pelvic region, respectively. The sensitivity, specificity, and accuracy of whole-body PET angiography for detecting vascular abnormalities were 75.9%, 98.8%, and 96.5%, respectively. CONCLUSIONS: Whole-body PET angiography showed a better image quality for the neck-to-chest and pelvic regions in this setting, although it provided limited information on the vessels in the abdominal region.

[Creation of a Stereo-paired Bone Anatomical Chart Using Human Bone Specimens for X-ray Anatomical Education Part III: Addition of Anaglyph Three-dimensional Images for Those Who Hardly See Stereo-paired Photographs with the Naked Eye].

We published a report entitled "Creation of a stereo-paired bone anatomical chart using human bone specimen for radiation education" in this journal in order to accurately understand the surface structure and three-dimensional structure of bones, and assist in bone image interpretation. However, some people cannot see stereoscopically with the naked eye. Therefore, we created anaglyph three-dimensional (3D) images from stereo-paired images of the stereo X-ray anatomical chart of the bone specimen. The anaglyph of the bone surface and X-ray images facilitates stereoscopic viewing with red-blue 3D glasses. The stereo X-ray anatomical chart of the bone specimen with anaglyph 3D images was converted into an electronic data file in the same manner as the stereo X-ray anatomical chart of the bone specimen, which can be easily used in any radiological examination rooms or at home through an electronic medium. We made it possible to perform correlative stereoscopic observations of the bone surface and X-ray images using red-blue 3D glasses.

[Creation of Bone X-ray Radiography Manual Using Human Bone Specimens for Bone X-ray Radiography Education].

Senior radiological technologists have made various improvements and have supported the clinical and educational fields by explaining bone X-ray radiography to students and junior radiological technologists to understand the procedure using illustrations, X-ray images, and photographs in a way that corresponds to the design software available for that era. Because human bone specimens are only available in the anatomy laboratory of medical schools, they could not be used for the explanation of bone X-ray radiography until now. Therefore, we have developed a bone X-ray radiography manual using bone specimens for the bone X-ray radiography education, which helps students to understand the procedure of bone X-ray radiography. Previous bone X-ray radiography manuals had not been illustrated by bone specimens and bone specimen X-ray images, but this bone X-ray radiography manual using bone specimens has made it possible to understand the surface morphology of bone specimens and X-ray images of them. In addition, the data of bone X-ray radiography using this bone specimen were made into an electronic file, which can be easily used at the place of radiological examination or at home through electronic media.

[Creation of Stereo-paired Color Vascular Anatomical Charts Using 3-dimentional Images].

Three-dimensional (3D) images of blood vessels in the human body, which are acquired by X-ray computed tomography (CT) and cone-beam CT of Angiography devices, are widely used in medical diagnosis and treatment. Using the 3DCT images of blood vessels, we created stereo-paired color vascular anatomical charts for better understanding of vascular anatomy in clinical settings, patient explanations, and student education. Since it is difficult to distinguish branches of blood vessels that show three-dimensionally complicated running such as cerebral blood vessels, we made it easier to identify them anatomically by color-coding each branch of the blood vessel. Also, by using stereo-paired images, we can see the three-dimensional blood vessel running. In the past anatomical books and vascular anatomy atlas, there was no anatomical chart of the whole body blood vessels that could be color-coded and stereoscopically viewed. We have made it possible to identify blood vessels by the stereoscopic vision of the blood vessels using this stereo-paired color anatomical chart. In addition, this vascular anatomical chart can be additionally revised according to the needs of the clinical and educational settings to be used, and the data can be converted into an electronic file so that it can be easily used in the field of radiological examination or at home through electronic media.