Neopentyl glycol-based radiohalogen-labeled amino acid derivatives for cancer radiotheranostics.

BACKGROUND: L-type amino acid transporter 1 (LAT1) is overexpressed in various cancers; therefore, radiohalogen-labeled amino acid derivatives targeting LAT1 have emerged as promising candidates for cancer radiotheranostics. However, 211At-labeled amino acid derivatives exhibit instability against deastatination in vivo, making it challenging to use 211At for radiotherapy. In this study, radiohalogen-labeled amino acid derivatives with high dehalogenation stability were developed. RESULTS: We designed and synthesized new radiohalogen-labeled amino acid derivatives ([211At]At-NpGT, [125I]I-NpGT, and [18F]F-NpGT) in which L-tyrosine was introduced into the neopentyl glycol (NpG) structure. The radiolabeled amino acid derivatives were recognized as substrates of LAT1 in the in vitro studies using C6 glioma cells. In a biodistribution study using C6 glioma-bearing mice, these agents exhibited high stability against in vivo dehalogenation and similar biodistributions. The similarity of [211At]At-NpGT and [18F]F-NpGT indicated that these pairs of radiolabeled compounds would be helpful in radiotheranostics. Moreover, [211At]At-NpGT exhibited a dose-dependent inhibitory effect on the growth of C6 glioma-bearing mice. CONCLUSIONS: [211At]At-NpGT exhibited a dose-dependent inhibitory effect on the tumor growth of glioma-bearing mice, and its biodistribution was similar to that of other radiohalogen-labeled amino acid derivatives. These findings suggest that radiotheranostics using [18F]F-NpGT and [123/131I]I-NpGT for diagnostic applications and [211At]At-NpGT and [131I]I-NpGT for therapeutic applications are promising.

Verification of image quality improvement of low-count bone scintigraphy using deep learning.

To improve image quality for low-count bone scintigraphy using deep learning and evaluate their clinical applicability. Six hundred patients (training, 500; validation, 50; evaluation, 50) were included in this study. Low-count original images (75%, 50%, 25%, 10%, and 5% counts) were generated from reference images (100% counts) using Poisson resampling. Output (DL-filtered) images were obtained after training with U-Net using reference images as teacher data. Gaussian-filtered images were generated for comparison. Peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) to the reference image were calculated to determine image quality. Artificial neural network (ANN) value, bone scan index (BSI), and number of hotspots (Hs) were computed using BONENAVI analysis to assess diagnostic performance. Accuracy of bone metastasis detection and area under the curve (AUC) were calculated. PSNR and SSIM for DL-filtered images were highest in all count percentages. BONENAVI analysis values for DL-filtered images did not differ significantly, regardless of the presence or absence of bone metastases. BONENAVI analysis values for original and Gaussian-filtered images differed significantly at ≦25% counts in patients without bone metastases. In patients with bone metastases, BSI and Hs for original and Gaussian-filtered images differed significantly at ≦10% counts, whereas ANN values did not. The accuracy of bone metastasis detection was highest for DL-filtered images in all count percentages; the AUC did not differ significantly. The deep learning method improved image quality and bone metastasis detection accuracy for low-count bone scintigraphy, suggesting its clinical applicability.

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.

Practice recommendation for measuring washout rates in 123I-BMIPP fatty acid images.

The purpose of this practice recommendation is to specifically identify the critical steps involved in performing and interpreting 123I-ß-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and measurement of washout rate (WR) from the heart. This document will cover backgrounds, patient preparation, testing procedure, visual image interpretation, quantitation methods using planar and SPECT studies, and reporting of WR. The pitfall and some tips for the calculation of 123I-BMIPP WR are also included. The targets of global and regional WR calculation include ischemic heart disease, cardiomyopathy, heart failure, and triglyceride deposit cardiomyovasculopathy, an emerging rare heart disease.

Practice Recommendation for Measuring Washout Rates in 123I-BMIPP Fatty Acid Images.

The purpose of this practice recommendation is to specifically identify the critical steps involved in performing and interpreting 123I-ß-methyl-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) and measurement of washout rate (WR) from the heart. This document will cover backgrounds, patient preparation, testing procedure, visual image interpretation, quantitation methods using planar and SPECT studies, and reporting of WR. The pitfall and some tips for the calculation of 123I-BMIPP WR are also included. The targets of global and regional WR calculation include ischemic heart disease, cardiomyopathy, heart failure, and triglyceride deposit cardiomyovasculopathy, an emerging rare heart disease.

Modified Algorithm Using Total Count for Calculating Myocardial Washout Rate in Single-Photon Emission Computerized Tomography.

Background: The arithmetic mean of washout rate (WR) (namely, AMWR) of each segment is a commonly used algorithm for calculating WR from a polar map in single-photon emission computerized tomography (SPECT). However, in this algorithm, uneven radiotracer uptake among segments affects WR calculation. To solve this possible issue, we formulated a modified algorithm for calculating WR based on the total count (namely, TCWR). Methods: The WR of iodine-123-ß-methyl-p-iodophenylpentadecanoic acid (BMIPP) was calculated using TCWR and AMWR, and WR values using TCWR and AMWR were compared by disease. Participants included those without cardiovascular diseases (normal), those with CD36 deficiency, triglyceride deposit cardiomyovasculopathy (TGCV), TGCV with old myocardial infarction (OMI), and non-TGCV with OMI. Results: WR values using TCWR and AMWR did not differ significantly in the following groups: normal, 27.4±8.5 and 27.3±8.5% (p=0.97); CD36 deficiency, -3.2±6.5 and -4.1±7.4% (p=0.81); TGCV, 2.4±6.3 and 2.2±6.3% (p=0.93); and TGCV with OMI, -0.9±7.6 and -3.7±8.4% (p=0.32). However, AMWR showed a lower WR than TCWR in non-TGCV with OMI (4.8±8.7 and 18.9±6.7%, p=0.0008). Conclusions: TCWR is suitable for calculating WR using SPECT polar maps even in cases with heterogeneous radiotracer uptake, such as OMIs. TCWR may be applied to measuring the WR of radiopharmaceuticals other than BMIPP in investigating the pathophysiology of heart diseases.

Optimization of the Attenuation Coefficient for Chang Attenuation Correction in 123I Brain Perfusion SPECT.

N-isopropyl-p-123I-iodoamphetamine brain perfusion SPECT has been used with various attenuation coefficients (µ-values); however, optimization is required. This study aimed to determine the optimal µ-value (µopt-value) for Chang attenuation correction (AC) using clinical data by comparing the Chang method and CT-based AC. Methods: We used 100 patients (reference group, 60; disease group, 40) who underwent N-isopropyl-p-123I-iodoamphetamine SPECT. SPECT images of the reference group were obtained to calculate the AC using the Chang method (µ-values, 0.07-0.20; 0.005 interval) and the CT-based method, both without scatter correction (SC) and with SC. The µopt-value with the smallest mean percentage error for the brain regions of the reference group was calculated. Agreement between the Chang and CT-based methods applying the µopt-value was evaluated using Bland-Altman analysis. Additionally, the percentage error in the region of hypoperfusion in the diseased group was compared with the percentage error in the same region in the reference group when the µopt-value was applied. Results: The µopt-values were 0.140 for Chang without SC and 0.160 for Chang with SC. In the Chang method, with the µopt-value applied, fixed and proportional biases were observed in the Bland-Altman analysis (both P < 0.05), and there was a tendency for the percentage error to be underestimated in the limbic regions and overestimated in the central brain regions. There was no significant difference between the disease group and the reference group in the region of hypoperfusion in either Chang without SC or Chang with SC. Conclusion: The present study revealed that the µopt-values of the Chang method are 0.140 without SC and 0.160 with SC.

[The Questionnaire Survey of Japanese Practice and Environment for Targeted Radionuclide Therapy in 2021].

PURPOSE: Recently, the targeted radionuclide therapy (TRT) was urgently required to adapt the practice and environment because of the implementation of novel therapeutic radiopharmaceuticals such as alpha- and beta- radionuclides therapy. The present study aimed to clarify the questionnaire survey with the current situation (safety controls for workers and patients) at Japanese TRT facilities. METHODS: The massive questionnaire survey, 2 months from October to November 2021, was conducted among nationwide 251 facilities that have performed TRT in the past two years. The alpha- and beta- therapeutic radiopharmaceuticals were categorized and answered by one representative of the facility under anonymity. We analyzed the actual situation of each facility related to occupational exposure, radiation protection, contamination inspection, patient release criteria, and dosimetry for TRT. RESULTS: The survey response rate was 69.1% (174 facilities). About 75% of these facilities reported that they either follow the guidelines or take their own measures to reduce occupational exposure. The confirmed means of patient release criteria were 68.0% with the administered radioactivity and 87.2% with the ambient dose rate. The cold run was not performed for the first time at 15.0% and 10.0% of the facilities for ß- and α-emitting radionuclides, respectively. The facilities without attachment syringe shields were 39.2% for alpha-radionuclides therapy and 20.3% for beta-radionuclides therapy. CONCLUSION: We clarified the Japanese problem for TRT practice and environment by the questionnaire survey. Our findings indicated that the Japanese guidelines and manuals for TRT were not partly followed in the nationwide facilities.

Determination of a reliable assessment for occupational eye lens dose in nuclear medicine.

The most recent statement published by the International Commission on Radiological Protection describes a reduction in the maximum allowable occupational eye lens dose from 150 to 20 mSv/year (averaged over 5-year periods). Exposing the eye lens to radiation is a concern for nuclear medicine staff who handle radionuclide tracers with various levels of photon energy. This study aimed to define the optimal dosimeter and means of measuring the amount of exposure to which the eye lens is exposed during a routine nuclear medicine practice. A RANDO human phantom attached to Glass Badge and Luminess Badge for body or neck, DOSIRIS and VISION for eyes, and nanoDot for body, neck, and eyes was exposed to 99m Tc, 123 I, and 18 F radionuclides. Sealed syringe sources of each radionuclide were positioned 30 cm from the abdomen of the phantom. Estimated exposure based on measurement conditions (i.e., air kerma rate constants, conversion coefficient, distance, activity, and exposure time) was compared measured dose equivalent of each dosimeter. Differences in body, neck, and eye lens dosimeters were statistically analyzed. The 10-mm dose equivalent significantly differed between the Glass Badge and Luminess Badge for the neck, but these were almost equivalent at the body. The 0.07-mm dose equivalent for the nanoDot dosimeters was greatly overestimated compared to the estimated exposure of 99m Tc and 123 I radionuclides. Measured dose equivalents of exposure significantly differed between the body and eye lens dosimeters with respect to 18 F. Although accurately measuring radiation exposure to the eye lenses of nuclear medicine staff is conventionally monitored using dosimeters worn on the chest or abdomen, eye lens dosimeters that provide a 3-mm dose equivalent near the eye would be a more reliable means of assessing radiation doses in the mixed radiation environment of nuclear medicine.

Dopaminergic Correlates of Regional Cerebral Blood Flow in Parkinsonian Disorders.

BACKGROUND: Cerebral blood flow (CBF) and dopamine transporter (DAT) images are clinically used for the differential diagnosis of parkinsonian disorders. OBJECTIVES: This study aimed to examine the correlation of CBF with striatal DAT in patients with Parkinson's disease (PD) and atypical parkinsonian syndromes (APS) and evaluate the diagnostic power of DAT-correlated CBF in PD through machine learning with each imaging modality alone or in combination. METHODS: Fifty-eight patients with PD and 71 with APS (24 with multiple system atrophy, 21 with progressive supranuclear palsy, and 26 with corticobasal syndrome) underwent 123 I-IMP and 123 I-FP-CIT single-photon emission computed tomography. Multiple regression analyses for CBF and striatal DAT binding were conducted on each group. PD probability was predicted by machine learning and receiver operating characteristic curves. RESULTS: The PD group showed more affected striatal DAT binding positively correlated with the ipsilateral prefrontal perfusion and negatively with the bilateral cerebellar perfusion. In corticobasal syndrome, striatal DAT binding positively correlated with the ipsilateral prefrontal perfusion and negatively with the contralateral precentral perfusion. In Richardson's syndrome, striatal DAT binding positively correlated with perfusion in the ipsilateral precentral cortex and basal ganglia. Machine learning showed that the combination of CBF and DAT was better for delineating PD from APS (area under the curve [AUC] = 0.87) than either CBF (0.67) or DAT (0.50) alone. CONCLUSIONS: In PD and four-repeat tauopathy, prefrontal perfusion was related to ipsilateral nigrostriatal dopaminergic function. This dual-tracer frontostriatal relationship may be effectively used as a diagnostic tool for delineating PD from APS. © 2022 International Parkinson and Movement Disorder Society.

The first case report of pediatric acute appendicitis caused by "Candidatus Actinobaculum timonae".

A 14-year-old boy presented to the hospital with pain in the right lower abdomen. His condition was diagnosed as acute appendicitis. An emergency operation was performed, and histopathological examination revealed an actinomycete-related organism in the excised appendicitis specimen. On 16S rRNA gene sequence analysis, "Candidatus Actinobaculum timonae" was identified, which is the first known case in a pediatric patient.

Development of attenuation correction methods using deep learning in brain-perfusion single-photon emission computed tomography.

PURPOSE: Computed tomography (CT)-based attenuation correction (CTAC) in single-photon emission computed tomography (SPECT) is highly accurate, but it requires hybrid SPECT/CT instruments and additional radiation exposure. To obtain attenuation correction (AC) without the need for additional CT images, a deep learning method was used to generate pseudo-CT images has previously been reported, but it is limited because of cross-modality transformation, resulting in misalignment and modality-specific artifacts. This study aimed to develop a deep learning-based approach using non-attenuation-corrected (NAC) images and CTAC-based images for training to yield AC images in brain-perfusion SPECT. This study also investigated whether the proposed approach is superior to conventional Chang's AC (ChangAC). METHODS: In total, 236 patients who underwent brain-perfusion SPECT were randomly divided into two groups: the training group (189 patients; 80%) and the test group (47 patients; 20%). Two models were constructed using Autoencoder (AutoencoderAC) and U-Net (U-NetAC), respectively. ChangAC, AutoencoderAC, and U-NetAC approaches were compared with CTAC using qualitative analysis (visual evaluation) and quantitative analysis (normalized mean squared error [NMSE] and the percentage error in each brain region). Statistical analyses were performed using the Wilcoxon signed-rank sum test and Bland-Altman analysis. RESULTS: U-NetAC had the highest visual evaluation score. The NMSE results for the U-NetAC were the lowest, followed by AutoencoderAC and ChangAC (P < 0.001). Bland-Altman analysis showed a fixed bias for ChangAC and AutoencoderAC and a proportional bias for ChangAC. ChangAC underestimated counts by 30-40% in all brain regions. AutoencoderAC and U-NetAC produced mean errors of <1% and maximum errors of 3%, respectively. CONCLUSION: New deep learning-based AC methods for AutoencoderAC and U-NetAC were developed. Their accuracy was higher than that obtained by ChangAC. U-NetAC exhibited higher qualitative and quantitative accuracy than AutoencoderAC. We generated highly accurate AC images directly from NAC images without the need for intermediate pseudo-CT images. To verify our models' generalizability, external validation is required.

[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.

The 2020 national diagnostic reference levels for nuclear medicine in Japan.

The diagnostic reference levels (DRLs) are one of several effective tools for optimizing nuclear medicine examinations and reducing patient exposure. With the advances in imaging technology and alterations of examination protocols, the DRLs must be reviewed periodically. The first DRLs in Japan were established in 2015, and since 5 years have passed, it is time to review and revise the DRLs. We conducted a survey to investigate the administered activities of radiopharmaceuticals and the radiation doses of computed tomography (CT) in hybrid CT accompanied by single photon emission computed tomography (SPECT)/CT and positron emission tomography (PET)/CT. We distributed a Web-based survey to 915 nuclear medicine facilities throughout Japan and survey responses were provided by 256 nuclear medicine facilities (response rate 28%). We asked for the facility's median actual administered activity and median radiation dose of hybrid CT when SPECT/CT or PET/CT was performed for patients with standard habitus in the standard protocol of the facility for each nuclear medicine examination. We determined the new DRLs based on the 75th percentile referring to the 2015 DRLs, drug package inserts, and updated guidelines. The 2020 DRLs are almost the same as the 2015 DRLs, but for the relatively long-lived radionuclides, the DRLs are set low due to the changes in the Japanese delivery system. There are no items set higher than the previous values. Although the DRLs determined this time are roughly equivalent to the DRLs used in the US, overall they tend to be higher than the European DRLs. The DRLs of the radiation dose of CT in hybrid CT vary widely depending on each imaging site and the purpose of the examination.