著者1:18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging
2: 18F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia
要旨1: Objective: Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine (18F-FPYBF-2)
has been validated as a tracer for amyloid imaging and it was found that 18F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al, 2018).
The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of 18F-FPYBF-2 in normal healthy volunteers as a first-in-man study. Methods:
Four normal healthy volunteers (male: 3, female: 1; mean age: 40 ± 17; age range: 25-56) were included and underwent 18F-FPYBF-2 PET/CT study for evaluation of radiation exposure and pharmacokinetics.
A 10-minutes dynamic PET/CT scan of the body (chest and abdomen) was performed at 0-10min and a 15-minutes whole-body static scan was performed 6 times after the injection of 18F-FPYBF-2.
After reconstructing PET and CT image data, individual organ time–activity curves were estimated by fitting volume of interest data from the dynamic scan and whole-body scans.
The OLINDA/EXM version 2.0 software was used to determine the whole-body effective doses. Results: Dynamic PET imaging demonstrated that the hepatobiliary and renal systems were the principal pathways of clearance of 18F-FPYBF-2.
High uptake in the liver and the gall bladder, the stomach, and the kidneys were demonstrated, followed by the intestines and the urinary bladder. The ED for the adult dosimetric model was estimated to be 8.48±1.25 Sv/MBq.
The higher absorbed doses were estimated for the liver (28.98±12.49 and 36.21±15.64 Gy/MBq), the brain (20.93±4.56 and 23.05±5.03Gy/MBq), the osteogenic cells (9.67±1.67 and 10.29±1.70 Gy/MBq),
the small intestines (9.12±2.61 and 11.12±3.15 Gy/MBq), and the kidneys (7.81±2.62 and 8.71±2.90 Gy/MBq) for male and female, respectively.
Conclusions: The ED for the adult dosimetric model was similar to those of other agents used for amyloid PET imaging.
The diagnostic dosage of 185-370 MBq of 18F-FPYBF-2 was considered to be acceptable for administration in patients as a diagnostic tool for the evaluation of AD.
2: Objective:Recently, we developed a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (18F-FPYBF-2) (Ono et al., J Med Chem 54:2971–9, 2011).
The aim of this study was to assess the feasibility of 18F-FPYBF-2 as an amyloid imaging PET tracer in a first clinical study with healthy volunteers and patients with various dementia and in comparative dual tracer study using 11C-Pittsburgh Compound B (11C-PiB).
Methods:61 healthy volunteers (age: 53.7 ± 13.1 years old; 19 male and 42 female; age range 24–79) and 55 patients with suspected dementia [Alzheimer’s Disease (AD); early AD: n = 19 and moderate stage AD:
n = 8, other dementia: n = 9, mild cognitive impairment (MCI): n = 16, cognitively normal: n = 3] for first clinical study underwent static head PET/CT scan using 18 F − FPYBF-2 at 50–70 min after injection.
13 volunteers and 14 patients also underwent dynamic PET scan at 0–50 min at the same instant.
16 subjects (volunteers: n = 5, patients with dementia: n = 11) (age: 66.3 ± 14.2 years old; 10 males and 6 females) were evaluated for comparative study (50–70 min after injection) using 18F-FPYBF-2 and 11C-PiB on separate days, respectively.
Quantitative analysis of mean cortical uptake was calculated using Mean Cortical Index of SUVR (standardized uptake value ratio) based on the established method for 11C-PiB analysis using cerebellar cortex as control.
Results:Studies with healthy volunteers showed that 18F-FPYBF-2 uptake was mainly observed in cerebral white matter and that average Mean Cortical Index at 50–70 min was low and stable (1.066 ± 0.069) basically independent from age or gender.
In patients with AD, 18F-FPYBF-2 uptake was observed both in cerebral white and gray matter, and Mean Cortical Index was significantly higher (early AD: 1.288 ± 0.134, moderate AD: 1.342 ± 0.191) than those of volunteers and other dementia (1...018 ± 0.057).
In comparative study, the results of 18F-FPYBF-2 PET/CT were comparable with those of 11C-PiB, and the Mean Cortical Index (18F-FPYBF-2: 1.173 ± 0.215; 11C-PiB: 1.435 ± 0.474) showed direct proportional relationship with each other (p < 0.0001).
Conclusions:Our first clinical study suggest that 18F-FPYBF-2 is a useful PET tracer for the evaluation of β-amyloid deposition and that quantitative analysis of Mean Cortical Index of SUVR is a reliable diagnostic tool for the diagnosis of AD.
2015年にWHO Classification of Tumors of The Lung, Pleura, Thymus and Heart 4th Editionが刊行され、組織分類(以下、新WHO分類)が改訂されたことをうけ、肺癌の細胞診断を国際標準に合わせるべく、新WHO分類に準拠した肺癌取扱い規約組織分類に沿ったワークショップを計画いたしました。
表題A case of thyroid papillary carcinoma: remarkable decrease in multiple lung metastases within 40 years after a single administration of radioiodine without thyroidectomy and with later anaplastic formation
要旨Differentiated thyroid carcinoma in childhood and adolescence is an uncommon malignancy, and unique to the overall favorable prognosis despite its relatively high rate of nodal and distant metastases.
Total thyroidectomy and positive 131I therapy are recommended for cases with pulmonary metastases. In contrast, anaplastic thyroid cancer is one of the most aggressive malignancies with a poor prognosis.
It is thought that anaplastic cancer arises from transformation of differentiated thyroid cancer, however the mechanism of dedifferentiation remains unclear.
We experienced a case of differentiated thyroid carcinoma with pulmonary metastases that remarkably decreased in size over a 40-year period after early administration of 131I for diagnosis without thyroidectomy.
At age 58, his cervical nodules were incidentally detected, and total thyroidectomy was performed along with subsequent administration of radioiodine therapy.
Although very intense accumulations were observed in both lungs, some of the nodules developed in anaplastic transformation over the next several years.
We report the long history of this case and discuss the relevant literatures.
著者Hiroshi Yamauchi, Shinya Kagawa, Masaaki Takahashi, and Tatsuya Higashi
表題Long-term hemodynamic changes and blood pressure in atherosclerotic major cerebral artery disease
要旨In patients with major cerebral artery disease, lower blood pressure might reduce blood flow in the collateral pathways, thereby impairing the growth of cerebral collaterals,
inhibiting hemodynamic improvement. We evaluated the hemodynamic status twice using positron emission tomography and 15O-gas, over time,
in 89 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery disease that had no ischemic episodes during follow-up (mean, 28+/-23 months).
Changes in the mean hemispheric values of hemodynamic parameters in the territory of the diseased artery at follow-up were correlated with the mean blood pressure values at the baseline and follow-up examinations.
There was a positive linear relationship between the degree of hemodynamic improvement and systolic blood pressure. Patients with low systolic blood pressure (<130 mmHg) (n=18) showed hemodynamic deterioration as indicated by significant decreases in cerebral blood flow,
cerebral blood flow/cerebral blood volume ratio, and increases in oxygen extraction fraction during follow-up. In contrast, there were no significant changes in patients without low systolic blood pressure.
In patients with atherosclerotic internal carotid artery or middle cerebral artery disease and no ischemic episodes of stroke during follow-up, lower systolic blood pressure was associated with lesser hemodynamic improvement.
1) Division of PET imaging, Shiga Medical Center Research Institute, 2) Graduate School of Medical Science, Kanazawa University, 3) Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences,
4) Graduate School of Pharmaceutical Sciences, Kyoto University, 5) Department of Analytical & Bioinorganic Chemistry, Kyoto Pharmaceutical University
要旨Objectives: Recently, we developed a benzofuran derivative for the imaging of β-amyloid (Aβ) plaques, 5-(5-(2-(2-(2-[18F]fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine ([18F]FPYBF-2).
To compare with [18F]FPYBF-2 study in clinical practice, the aim of this study was to assess the radiosynthesis,
quality control and safety assessment of the loop labeling method using a cassette-type multipurpose automatic synthesizer module for radiosynthesis of [11C]Pittsburg compound B ([11C]PiB).
Methods: The radiosynthesis of [11C]PiB was performed on a hybrid synthesizer, cassette-type multipurpose automatic synthesizer module (JFE Engineering Corporation).
[11C]Methyl triflate was trapped in a loop of sterilized spiral type (Lectro-Cath, Vigon) precharged with 1 mg of precursor, 2-(4’Aminophenyl)-6-hydroxybenzothiazole in 60 μL of Cyclohexanone and reacted for 1 min at room temperature after radioactivity peaks in the loop.
After purification of the crude product by HPLC, [11C]PiB was eluted with 2.5% ethanol in saline. The quality control tests of final products and safety assessment were performed.
Results: [11C]PiB for the loop labeling method was produced with radioactivity of 12.2 ± 0.9 GBq, total synthesis time of 26.6 ± 0.2 min, radiochemical yield (decay uncorrected) of 38.7 ± 1.5 %,
radiochemical purity of > 99.9 % and specific activity of 95.5 ± 10.1 GBq/μmol.
The products satisfied the relevant quality standard such as the Quality Control of [18F]FDG. There was no harmful finding at a single dose toxicity test (radiolabeled final products).
Conclusion: By the loop labeling method using a cassette-type multipurpose automatic synthesizer module,
the synthesis of [11C]PiB for clinical grade was successfully implemented in our study with healthy volunteers and patients with dementia.
著者 Atsushi Fukuda, Nao Ichikawa, Yoshiharu Fujita, Pei-Jan Paul Lin, Kosuke Matsubara, and Tosiaki Miyati
標題Does gantry rotation time influence accuracy of volume computed tomography dose index (CTDIvol) in modern CT?
要旨The purpose of this study was to develop a gantry overrun corrected CTDIvol (cCTDIvol) dosimetry and evaluate the differences between the displayed CTDIvol (dCTDIvol),
measured CTDIvol (mCTDIvol), and the cCTDIvol. The each 8 rotation times between 275 and 1000 ms of two CT scanners were investigated.
Rotation time (Trot) and the beam-on time (Tbeam) in axial scanning were measured accurately to determine the gantry overrun time (Tover) as Tbeam − Trot. Subsequently, mCTDIvol was measured by using a 100 mm ionization chamber and CTDI phantoms.
Furthermore, we introduced a gantry overrun correction factor (Co = Trot/Tbeam) to obtain cCTDIvol.
Upon completion of the data acquisition, the dCTDIvol and mCTDIvol were compared with the cCTDIvol.
The discrepancies of Trot were 0.2 ± 0.2 ms as compared to the preset rotation times, and Tover was machine-specific and almost constant (22.4 ± 0.5 ms or 45.1 ± 0.3 ms) irrespective of the preset rotation time.
Both dCTDIvol and mCTDIvol were increasingly overestimated compared to cCTDIvol as the faster the preset rotation time was selected (1.7–23.5%).
The rotation time influences the accuracy of CTDIvol in modern CT, and should be taken into consideration when assessing the radiation output in modern CT.
福田主査がJapan Radiology Congress (JRC) 2017合同シンポジウム小児画像診断における被ばくの現状と課題で講演しました。