Evaluation of PET/CT imaging with [89Zr]Zr-DFO-girentuximab: a phase 1 clinical study in Japanese patients with renal cell carcinoma (Zirdac-JP).

BACKGROUND: PET/CT imaging with Zirconium-89 labeled [89Zr]Zr-DFO-girentuximab, which targets tumor antigen CAIX, may aid in the differentiation and characterization of clear cell renal cell carcinomas (RCC) and other renal and extrarenal lesions, and has been studied in European and American cohorts. We report results from a phase I study that evaluated the safety profile, biodistribution, and dosimetry of [89Zr]Zr-DFO-girentuximab in Japanese patients with suspected RCC. METHODS: Eligible adult patients received 37 MBq (± 10%; 10 mg mass dose) of intravenous [89Zr]Zr-DFO-girentuximab. Safety and tolerability profile was assessed based on adverse events, concomitant medications, physical examination, vital signs, hematology, serum chemistry, urinalysis, human anti-chimeric antibody measurement, and 12-lead electrocardiograms at predefined intervals. Biodistribution and normal organ and tumor dosimetry were evaluated with PET/CT images acquired at 0.5, 4, 24, 72 h and Day 5 ± 2 d after administration. RESULTS: [89Zr]Zr-DFO-girentuximab was administered in six patients as per protocol. No treatment-emergent adverse events were reported. Dosimetry analysis showed that radioactivity was widely distributed in the body, and that the absorbed dose in healthy organs was highest in the liver (mean ± standard deviation) (1.365 ± 0.245 mGy/MBq), kidney (1.126 ± 0.190 mGy/MBq), heart wall (1.096 ± 0.232 mGy/MBq), and spleen (1.072 ± 0.466 mGy/MBq). The mean effective dose, adjusted by the radioactive dose administered, was 0.470 mSv/MBq. The radiation dose was highly accumulated in the targeted tumor, while any abnormal accumulation in other organs was not reported. CONCLUSIONS: This study demonstrates that [89Zr]Zr-DFO-girentuximab administered to Japanese patients with suspected RCC has a favorable safety profile and is well tolerated and has a similar dosimetry profile to previously studied populations.

Novel nomogram developed for determining suitability of metastatic castration-resistant prostate cancer patients to receive maximum benefit from radium-223 dichloride treatment-Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial.

PURPOSE: To develop a novel nomogram for determining radium-223 dichloride (Ra-223) treatment suitability for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: This Japanese Ra-223 Therapy in Prostate Cancer using Bone Scan Index (J-RAP-BSI) Trial was a retrospective multicenter investigation enrolled 258 mCRPC patients in Japan with Ra-223 treatment between June 2016 and August 2020, with bone scintigraphy findings before treatment, clinical data, and survival outcome available. A nomogram was constructed using prognostic factors for overall survival (OS) based on a least absolute shrinkage and selection operator Cox regression model. A sub-analysis was also conducted for patients meeting European Medicines Agency (EMA) guidelines. RESULTS: Within a median of 17.4 months after initial Ra-223 treatment, 124 patients (48.1%) died from prostate cancer. Predictive factors included (1) sum of prior treatment history (score 0, never prior novel androgen receptor-targeted agents (ARTA) therapy, never prior taxane-based chemotherapy, and ever prior bisphosphonate/denosumab treatment), (2) Eastern Cooperative Oncology Group (ECOG) performance status, (3) prostate-specific antigen doubling time (PSADT), (4) hemoglobin, (5) lactate dehydrogenase (LDH), and (6) alkaline phosphatase (ALP) levels, and (7) automated bone scan index (aBSI) value based on bone scintigraphy. The nomogram using those factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.748 and 0.734, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.771, 0.818, and 0.771, respectively. In 227 patients meeting EMA recommendation, the nomogram with seven factors showed good discrimination, with apparent and optimism-corrected Harrell's concordance index values of 0.722 and 0.704, respectively. Time-dependent area under the curve values at 1, 2, and 3 years were 0.747, 0.790, and 0.759, respectively. CONCLUSION: This novel nomogram including aBSI to select mCRPC patients to receive Ra-223 with significantly prolonged OS possibility was found suitable for assisting therapeutic decision-making, regardless of EMA recommendation.

Cardiac overload resolved by resection of a large plexiform neurofibroma on both the buttocks and upper posterior thighs in a patient with neurofibromatosis type I: a case report.

BACKGROUND: A large plexiform neurofibroma in patients with neurofibromatosis type I can be life threatening due to possible massive bleeding within the lesion. Although the literature includes many reports that describe the plexiform neurofibroma size and weight or strategies for their surgical treatment, few have discussed their possible physical or mental benefits, such as reducing cardiac stress. In addition, resection of these large tumors can result in impaired wound healing, partly due to massive blood loss during surgery. CASE PRESENTATION: A 24-year-old man was diagnosed with neurofibromatosis type I and burdened with a large plexiform neurofibroma on the buttocks and upper posterior thighs. The patient was 159 cm in height and 70.0 kg in weight at the first visit. Cardiac overload was indicated by an echocardiography before surgery. His cardiac output was 5.2 L/min with mild tricuspid regurgitation. After embolism of the arteries feeding the tumor, the patient underwent surgery to remove the neurofibroma, followed by skin grafting. Follow-up echocardiography, performed 6 months after the final surgery, indicated a decreased cardiac output (3.6 L/min) with improvement of tricuspid regurgitation. Because the blood loss during the first surgery was over 3.8 L, malnutrition with albuminemia was induced and half of the skin graft did not attach. Nutritional support to improve the albuminemia produced better results following a second surgery to repair the skin wound. CONCLUSION: Cardiac overload may be latent in patients with neurofibromatosis type I with large plexiform neurofibromas. As in pregnancy, the body may compensate for this burden. In these patients, one stage total excision may improve quality of life and reduce cardiac overload. In addition, nutritional support is likely needed following a major surgery that results in either an extensive skin wound or excessive blood loss during treatment.

Quantification of temporal changes in calcium score in active atherosclerotic plaque in major vessels by 18F-sodium fluoride PET/CT.

PURPOSE: Our aim was to assess whether 18F-NaF PET/CT is able to predict progression of the CT calcium score. METHODS: Between August 2007 and November 2015, 34 patients (18 women, 16 men; age, mean ± standard deviation, 57.5 ± 13.9 years; age range 19-78 years) with malignancy or orthopaedic disease were enrolled in this study, with approximately 1-year follow-up data. Baseline and follow-up CT images were retrospectively evaluated for the presence of calcification sites in major vessel walls. The maximum and mean CT values (CTmax and CTmean, in Hounsfield units), calcification volumetric score (CVS, in cubic millimetres) and Agatston units score (AU) were evaluated for each site. Subsequent changes in CTmax, CTmean, CVS and AU were calculated and expressed as ΔCTmax, ΔCTmean, ΔCVS and ΔAU, respectively. We then evaluated the relationship between 18F-NaF uptake (using the maximum target-to-background ratio, TBRmax, and the maximum blood-subtracted 18F-NaF activity, bsNaFmax, which was obtained by subtracting the SUVmax of each calcified plaque lesion and NaF-avid site from the SUVmean in the right atrium blood pool) and the change in calcified plaque volume and characteristics obtained after 1 year. RESULTS: We detected and analysed 182 calcified plaque sites and 96 hot spots on major vessel walls. 18F-NaF uptake showed very weak correlations with CTmax, CTmean, CVS, CVS after 1 year, AU and AU after 1 year on both baseline and follow-up PET/CT scans for each site. 18F-NaF uptake showed no correlation with ΔCTmax or ΔCTmean. However, there was a significant correlation between the intensity of 18F-NaF uptake and ΔCVS and ΔAU. CONCLUSION: 18F-NaF uptake has a strong correlation with calcium score progression which was a predictor of future cardiovascular disease risk. PET/CT using 18F-NaF may be able to predict calcium score progression which is known to be the major characteristic of atherosclerosis.

Stomach position evaluated using computed tomography is related to successful post-pyloric enteral feeding tube placement in critically ill patients: a retrospective observational study.

BACKGROUND: Post-pyloric enteral feeding reduces respiratory complications and shortens the duration of mechanical ventilation. Blind placement of post-pyloric enteral feeding tubes (EFT) in patients with critical illnesses is often the first-line method because endoscopy or fluoroscopy cannot be easily performed at bedside; however, difficult placements regularly occur. We reported an association between the stomach position caudal to spinal level L1-L2, evaluated by abdominal radiographs after placement, and difficult placement; however, this method could not indicate difficulty before EFT placement. The aim of our study was to evaluate the association between stomach position, estimated using computed tomography (CT) images taken before the blind placement of the post-pyloric EFT, and the difficulty of EFT placement. METHODS: Data from patients aged ≥ 20 years who underwent post-pyloric EFT in our intensive care unit were obtained retrospectively. Logistic regression analysis was used to evaluate the association between successful initial EFT placement and explanatory variables, including stomach position estimated by CT. Two cut-off values were used: caudal to L1-L2 based on a previous study and the best cut-off value calculated by the receiver operating characteristic curve. Variable selection was performed backward stepwise using Akaike's Information Criterion. RESULTS: Of the total of 453 patients who were enrolled, the success rate of the initial EFT placement was 43.5%. The adjusted odds ratio for successful initial EFT placement of the stomach position caudal to L1-L2 was 0.61 (95% confidence interval: 0.41-1.07). Logistic regression analysis, including the stomach position caudal to L2-L3, calculated as the best cut-off value, indicated that stomach position was an independent factor for failure of initial EFT placement (adjusted odds ratio, 0.55; 95% confidence interval: 0.33-0.91). CONCLUSIONS: Stomach position evaluated using CT images was associated with successful initial post-pyloric EFT placement. The best cut-off value of the greater curvature of the stomach to predict the success or failure of the first attempt was spinal level L2-L3. Trial registration University Hospital Medical Information Network Clinical Trials Registry (UMIN000046986; February 28, 2022). https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000052151.

Assessing Therapeutic Response to Radium-223 with an Automated Bone Scan Index among Metastatic Castration-Resistant Prostate Cancer Patients: Data from Patients in the J-RAP-BSI Trial.

To evaluate the usefulness of change in the automated bone scan index (aBSI) value derived from bone scintigraphy findings as an imaging biomarker for the assessment of treatment response and survival prediction in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Ra-223. This study was a retrospective investigation of a Japanese cohort of 205 mCRPC patients who received Ra-223 in 14 hospitals between July 2016 and August 2020 and for whom bone scintigraphy before and after radium-223 treatment was available. Correlations of aBSI change, with changes in the serum markers alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were evaluated. Additionally, the association of those changes with overall survival (OS) was assessed using the Cox proportional-hazards model and Kaplan-Meier curve results. Of the 205 patients enrolled, 165 (80.5%) completed six cycles of Ra-223. Following treatment, ALP decline (%ALP < 0%) was noted in 72.2% (148/205), aBSI decline (%aBSI < 0%) in 52.7% (108/205), and PSA decline (%PSA < 0%) in 27.8% (57/205). Furthermore, a reduction in both aBSI and ALP was seen in 87 (42.4%), a reduction in only ALP was seen in 61 (29.8%), a reduction in only aBSI was seen in 21 (10.2%), and in both aBSI and ALP increasing/stable (≥0%) was seen in 36 (17.6%) patients. Multiparametric analysis showed changes in PSA [hazard ratio (HR) 4.30, 95% confidence interval (CI) 2.32-8.77, p < 0.0001], aBSI (HR 2.22, 95%CI 1.43-3.59, p = 0.0003), and ALP (HR 2.06, 95%CI 1.35-3.14, p = 0.0008) as significant prognostic factors for OS. For mCRPC patients treated with Ra-223, aBSI change is useful as an imaging biomarker for treatment response assessment and survival prediction.

Comparison of CO-RADS Scores Based on Visual and Artificial Intelligence Assessments in a Non-Endemic Area.

In this study, we first developed an artificial intelligence (AI)-based algorithm for classifying chest computed tomography (CT) images using the coronavirus disease 2019 Reporting and Data System (CO-RADS). Subsequently, we evaluated its accuracy by comparing the calculated scores with those assigned by radiologists with varying levels of experience. This study included patients with suspected SARS-CoV-2 infection who underwent chest CT imaging between February and October 2020 in Japan, a non-endemic area. For each chest CT, the CO-RADS scores, determined by consensus among three experienced chest radiologists, were used as the gold standard. Images from 412 patients were used to train the model, whereas images from 83 patients were tested to obtain AI-based CO-RADS scores for each image. Six independent raters (one medical student, two residents, and three board-certified radiologists) evaluated the test images. Intraclass correlation coefficients (ICC) and weighted kappa values were calculated to determine the inter-rater agreement with the gold standard. The mean ICC and weighted kappa were 0.754 and 0.752 for the medical student and residents (taken together), 0.851 and 0.850 for the diagnostic radiologists, and 0.913 and 0.912 for AI, respectively. The CO-RADS scores calculated using our AI-based algorithm were comparable to those assigned by radiologists, indicating the accuracy and high reproducibility of our model. Our study findings would enable accurate reading, particularly in areas where radiologists are unavailable, and contribute to improvements in patient management and workflow.

Feasibility of prognosis assessment for cancer of unknown primary origin using texture analysis of 18F-fluorodeoxyglucose PET/computed tomography images of largest metastatic lymph node.

OBJECTIVE: Cancers of unknown primary origin cannot be staged using images, making the prognosis difficult. We attempted to predict prognosis of patients with unknown primary origin using tumour heterogeneity recently introduced in F-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT). METHODS: Overall, 30 patients with unknown primary origin who underwent whole-body F-FDG PET/CT scans were retrospectively enrolled for texture analysis. The volume of interest was placed in the largest metastatic lymph nodes and conventional parameters and grey-level co-occurrence matrix (GLCM) were calculated. Statistical analysis of image-based variables was performed using Cox regression analyses. Patients were stratified into two groups based on cutoff values of GLCMentropy obtained using receiver operating characteristics (ROCs). Patients were analyzed, and overall survival (OS) was compared using Kaplan-Meier analysis. RESULTS: Univariate Cox regression analysis showed significant differences in prognosis for parenchymal organ metastasis (P < 0.01), GLCM homogeneity (P = 0.01), GLCMcontrast (P < 0.01), GLCMentropy (P < 0.01) and GLCMdissimilarity (P < 0.01). Multivariate Cox regression analysis showed a significant difference in reduced prognosis for GLCMentropy positive (P < 0.01). Stratification was performed based on the GLCMentropy cutoff value, determined using ROCs analysis, with smaller groups showing better OS. CONCLUSIONS: Despite previous difficulties in predicting prognosis in patients with unknown primary origin, F-FDG PET/CT texture features may enable stratification of prognosis. This could be useful for appropriate patient selection and management and help identify a subset of patients with favourable outcomes. These novel findings may be helpful for prognostication and improving patient care.

Imaging of COVID-19: An update of current evidences.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been reported as a global emergency. As respiratory dysfunction is a major clinical presentation of COVID-19, chest computed tomography (CT) plays a central role in the diagnosis and management of patients with COVID-19. Recent advances in imaging approaches using artificial intelligence have been essential as a quantification and diagnostic tool to differentiate COVID-19 from other respiratory infectious diseases. Furthermore, cardiovascular involvement in patients with COVID-19 is not negligible and may result in rapid worsening of the disease and sudden death. Cardiac magnetic resonance imaging can accurately depict myocardial involvement in SARS-CoV-2 infection. This review summarizes the role of the radiology department in the management and the diagnosis of COVID-19, with a special emphasis on ultra-high-resolution CT findings, cardiovascular complications and the potential of artificial intelligence.

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.

Improved Diagnostic Accuracy of Bone Metastasis Detection by Water-HAP Associated to Non-contrast CT.

We examined whether water-hydroxyapatite (HAP) images improve the diagnostic accuracy of bone metastasis compared with non-contrast CT alone. We retrospectively evaluated dual-energy computed tomography (DECT) images of 83 cancer patients (bone metastasis, 31; without bone metastasis, 52) from May 2018 to June 2019. Initially, two evaluators examined for bone metastasis on conventional CT images. In the second session, both CT and CT images plus water-HAP images on DECT. The confidence of bone metastasis was scored from 1 (benign) to 5 (malignant). The sensitivity, specificity, positive predictive values, and negative predictive values for both modalities were calculated based on true positive and negative findings. The intra-observer area under curve (AUC) for detecting bone metastasis was compared by receiver operating characteristic analysis. Kappa coefficient calculated the inter-observer agreement. In conventional CT images, sensitivity, specificity, positive predictive value, and negative predictive value of raters 1 and 2 for the identification of bone metastases were 0.742 and 0.710, 0.981 and 0.981, 0.958 and 0.957, and 0.864 and 0.850, respectively. In water-HAP, they were 1.00 and 1.00, 0.981 and 1.00, 0.969 and 1.00, and 1.00 and 1.00, respectively. In CT, AUCs were 0.861 and 0.845 in each observer. On water-HAP images, AUCs were 0.990 and 1.00. Kappa coefficient was 0.964 for CT and 0.976 for water-HAP images. The combination of CT and water-HAP images significantly increased diagnostic accuracy for detecting bone metastasis. Water-HAP images on DECT may enable accurate initial staging, reduced radiation exposure, and cost.

Visualization of AMPA receptors in living human brain with positron emission tomography.

Although aberrations in the number and function of glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors are thought to underlie neuropsychiatric disorders, no methods are currently available for visualizing AMPA receptors in the living human brain. Here we developed a positron emission tomography (PET) tracer for AMPA receptors. A derivative of 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide radiolabeled with 11C ([11C]K-2) showed specific binding to AMPA receptors. Our clinical trial with healthy human participants confirmed reversible binding of [11C]K-2 in the brain according to Logan graphical analysis (UMIN000020975; study design: non-randomized, single arm; primary outcome: dynamics and distribution volumes of [11C]K-2 in the brain; secondary outcome: adverse events of [11C]K-2 during the 4-10 d following dosing; this trial met prespecified endpoints). In an exploratory clinical study including patients with epilepsy, we detected increased [11C]K-2 uptake in the epileptogenic focus of patients with mesial temporal lobe epilepsy, which was closely correlated with the local AMPA receptor protein distribution in surgical specimens from the same individuals (UMIN000025090; study design: non-randomized, single arm; primary outcome: correlation between [11C]K-2 uptake measured with PET before surgery and AMPA receptor protein density examined by biochemical study after surgery; secondary outcome: adverse events during the 7 d following PET scan; this trial met prespecified endpoints). Thus, [11C]K-2 is a potent PET tracer for AMPA receptors, potentially providing a tool to examine the involvement of AMPA receptors in neuropsychiatric disorders.

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.