Phase I clinical study of NMB58, a novel positron emission tomography (PET)-myocardial perfusion imaging tracer, conducted to evaluate its safety and pharmacokinetics in Japanese healthy adult males.

OBJECTIVES: NMB58 is a novel positron emission tomography (PET) tracer containing flurpiridaz as an active ingredient and available as a myocardial perfusion imaging tracer that targets mitochondrial complex 1. A phase I clinical study of NMB58 was conducted to evaluate its safety and pharmacokinetics in healthy volunteers. METHODS: Ten healthy Japanese volunteers received bolus injection of NMB58 (111-167 MBq) intravenously and underwent imaging studies at rest on day 1. Of these subjects, 5 (day 2 cohort 1; exercise stress) and 5 (day 2 cohort 2; pharmacological stress) similarly underwent stress imaging studies on day 2. The safety of NMB58 was evaluated through monitoring of signs/symptoms, electrocardiography, vital signs, and laboratory examinations at baseline and several time points during 3 days. Sequential whole-body positron emission tomography-computed tomography (PET/CT) scan data were acquired for up to 5-h post-injection, with venous blood and urine samples collected for up to 8-h post-injection. Based on the results of the biodistribution study, the absorbed radiation dose (Rad) was estimated by the Medical Internal Radiation Dose method. RESULTS: On day 1, the kidneys were shown to have the highest Rad, followed by the myocardium. On day 2, the myocardium was shown to have the highest Rad, followed by the kidneys. The mean effective doses (EDs) per unit activity administered were 0.021, 0.017 and 0.021 mSv/MBq for overall subjects (day 1), day 2 cohort 1 and day 2 cohort 2, respectively. The estimated exposure dose of NMB58 was similar to or lower than those of radiotracers currently approved for clinical use, including 18F-Fludeoxyglucose. Biodistribution results indicated that NMB58 distributed to the myocardium exhibited high and sustained retention after administration. The cumulative urinary radioactivity excretion rate was shown to be 6.9, 2.3%, and 8.0% of the injected dose in overall subjects (day 1), day 2 cohort 1 and day 2 cohort 2. There were no drug-related adverse events, and the tracer was well tolerated in all subjects. CONCLUSIONS: Based on radiation dosimetry, biodistribution, and safety evaluations, NMB58 was found to be a suitable tracer for clinical use in PET myocardial perfusion imaging during exercise or pharmacological stress.

Redox reaction and clinical outcome of primary diffuse large B-cell lymphoma of the central nervous system: Prognostic role of metabolic and textural parameters of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET/computed tomography in a small patient cohort.

OBJECTIVE: This study aimed to clarify the relationship between tumor redox reaction evaluated by Cu-diacetyl-bis (N4-methylthiosemicarbazone) (Cu-ATSM) PET/computed tomography (CT) and disease-free survival (DFS) in patients with primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS). METHODS: Fifteen consecutive patients with histologically confirmed DLBCL-CNS underwent preoperative Cu-ATSM PET/CT and F-fluorodeoxyglucose (FDG) PET/CT. Statistical features of seven first-order parameters, including the standardized uptake value (SUV); 12 second-order parameters, including gray-level co-occurrence matrices and gray-level zone size matrices; and 5 high-order parameters, including neighborhood gray-tone difference matrices, were calculated from the volume of interest. We compared DFS with parameters, including SUVmax and tumor-to-background (T/B) ratio of FDG, and SUVmax, T/B ratio, and other textural features of Cu-ATSM. RESULTS: The mean follow-up duration after PET/CT was 458 (range, 41-1071) days. The SUVmax of FDG was significantly higher than that of Cu-ATSM (P = 0.001), but the T/B ratio was not significantly different between the scans (3.49 ± 2.29 vs 2.48 ± 1.18; P = 0.244). A Mantel-Cox log-rank test revealed no significant association between SUVmax of FDG and DFS (P = 0.641). A high SUVmax of Cu-ATSM had a tendency of shorter DFS (P = 0.055). Total lesion reduction, reductive tumor volume, and T/B ratio of Cu-ATSM were significantly correlated with poor DFS by univariate analysis (P = 0.049, 0.031, and 0.007, respectively). Neighborhood gray-level co-occurrence matrix dissimilarity was significantly correlated with poor DFS (P = 0.015). CONCLUSIONS: Metabolic and textural features derived from pretreatment Cu-ATSM PET/CT could be used for predicting DFS and establishing a novel treatment strategy in DLBCL-CNS patients.

Tumor Identification of Less Aggressive or Indolent Lymphoma With Whole-Body 11C-Acetate PET/CT.

PURPOSE: The aim of this study was to investigate the diagnostic performance of whole-body [C]acetate PET/CT in less aggressive or indolent lymphomas, wherein [F]FDG PET/CT would exhibit limited sensitivity. METHODS: Between September 2016 and May 2018, we prospectively evaluated 17 patients (9 men, 8 women; mean age [range], 71 [45-87] years) with pathologically proven less aggressive or indolent lymphomas according to Non-Hodgkin's Lymphoma Classification Project, using both [F]FDG PET/CT and [C]acetate PET/CT (performed on the same day). Detected nodal lesions were recorded according to the Ann Arbor classification. Extranodal (EN) lesions were also evaluated. We compared whole-body lesion detection between [F] FDG PET/CT and [C]acetate PET/CT using the McNemar test. RESULTS: In all patients, significantly more nodal and EN lesions were detected using [C]acetate PET/CT than [F]FDG PET/CT (nodal: 84 vs 64 regions; P < 0.001; EN: 26 vs 19 regions, P = 0.039). Bone lesions were detected in 8 and 5 patients using [C]acetate PET/CT and [F]FDG PET/CT, respectively (P = 0.25). Among the 14 patients (82.4%) who underwent bone marrow biopsy, bone marrow involvement was detected with sensitivities of 100% (6/6 patients) and 80% (5/6 patients) using [C]acetate PET/CT and [F]FDG PET/CT, respectively. Multiple areas of focal uptake in the spleen of 1 patient were exhibited on [F]FDG PET/CT but not [C]acetate PET/CT. CONCLUSIONS: [C]acetate PET/CT exhibited greater sensitivity than [F]FDG PET/CT for lesion detection in patients with less aggressive or indolent lymphomas, thus promising applicability as a physiological tracer in the study of such lesions.

Takayasu arteritis: clinical importance of extra-vessel uptake on FDG PET/CT.

BACKGROUND: [F-18]fluorodeoxyglucose positron emission tomography/computed tomography is routinely used for assessing Takayasu arteritis patients. However, extra-vessel [F-18]fluorodeoxyglucose uptake has not been evaluated in detail in these patients. We aimed to describe the extent and distribution of extra-vascular [F-18]fluorodeoxyglucose uptake on positron emission tomography/computed tomography in Takayasu arteritis patients. Seventy-three [F-18]fluorodeoxyglucose positron emission tomography/computed tomography scans from 64 consecutive Takayasu arteritis patients (59 women, mean age, 35.4 years; range, 13 to 71 years) and 40 scans from age-matched controls (36 women, mean age, 37.8 years; range, 13 to 70 years) were examined. We graded [F-18]fluorodeoxyglucose uptake in large vessels using a 4-point scale and evaluated extra-vessel findings. Factors correlated with disease activity were examined. We evaluated the relationship between disease activity according to the National Institutes of Health score with extra-vessel findings, as well as other inflammatory markers (e.g., white blood cell count and C-reactive protein level). RESULTS: Extra-vessel involvement was present in 50 of 73 (68.4%) scans, specifically at the following sites: lymph nodes, 1.4%; thyroid glands, 17.8%; thymus, 11.0%; spleen, 1.4%; vertebrae, 45.2%; and pelvic bones, 9.6%. Takayasu arteritis patients had higher [F-18]fluorodeoxyglucose uptake in the spine (P = 0.03) and thyroid glands (P = 0.003) than did controls; uptake in other regions was comparable between groups. Compared with inactive patients, those with active Takayasu arteritis had a higher number of [F-18]fluorodeoxyglucose uptake sites in the vasculature (P = 0.001). Finally, patients with a National Institutes of Health score of ≥ 1 had significantly higher extra-vascular involvement (P = 0.008). CONCLUSIONS: Extra-vessel [F-18]fluorodeoxyglucose uptake may be present in the context of Takayasu arteritis-related inflammatory processes. Information on extra-vascular [F-18]fluorodeoxyglucose uptake may be useful for detecting and evaluating inflammatory processes when interpreting positron emission tomography/computed tomography scans obtained from Takayasu arteritis patients.

Standardization of [F-18]FDG PET/CT for response evaluation by the Radiologic Society of North America-Quantitative Imaging Biomarker Alliance (RSNA-QIBA) profile: preliminary results from the Japan-QIBA (J-QIBA) activities for Asian international multicenter phase II trial.

PURPOSE: In an Asian international multicenter phase II trial conducted in patients with peripheral T-cell lymphoma (PTCL), [F-18]FDG-PET/CT was used for evaluation of the therapeutic response. Standardization of the PET/CT scanners was necessary before patient enrollment. We therefore standardized the scanners by phantom tests based on the profile approved by the Quantitative Imaging Biomarkers Alliance (QIBA) of Radiological Society of North America (RSNA). MATERIALS AND METHODS: The tests were conducted on 12 scanners in 12 facilities in compliance with the QIBA Profile and used National Electrical Manufacturers Association (NEMA) International Electrotechnical Commission (IEC) body phantoms. We measured three parameters (standardized uptake value [SUV], resolution and noise) and adjusted the imaging parameter values. The indexes recommended in the Japanese Society of Nuclear Medicine (JSNM) guideline were also evaluated. RESULTS: In a total of 12 facilities, 6 facilities required no change in imaging conditions and 6 facilities required changes in imaging parameters. After revision, the three measurements (SUV, resolution and noise) met QIBA criteria at all sites, but 10 of the 12 scanners did not meet JSNM criteria. CONCLUSION: We standardized imaging conditions using phantoms as required in the RSNA-QIBA profile for response evaluation by [F-18]FDG PET/CT images in a multicenter study.

Apparent diffusion coefficient value as a biomarker reflecting morphological and biological features of prostate cancer.

PURPOSE: To assess whether there is an association between the apparent diffusion coefficient (ADC) value and the pathological characteristics of prostate cancer. METHODS: The study cohort consisted of 29 consecutive patients with prostate cancer treated with radical prostatectomy. All patients underwent diffusion-weighted MRI before the prostate biopsy. In 42 tumor foci, the associations of the ADC values with the clinicopathological characteristics and Ki-67 labeling index (LI) were analyzed. RESULTS: High-grade cancers (Gleason score [GS] ≥ 4 + 3), larger cancers (maximum diameter (MD) ≥ 16 mm), and highly proliferating cancers (Ki-67 LI ≥ 4.43 %) had significantly lower ADC values, respectively (P < .001, P = .008, and P = .044, respectively). There was no significant difference in ADC value according to age, prostate-specific antigen, presence of extra-prostatic extension, and intra-tumoral stroma proportion. Multivariate analysis showed that GS, Ki-67 LI, and MD had independent and significant correlations with ADC value (P < .001, P = .006, and P = .002, respectively). Low ADC tumors (<0.52 × 10(-3) mm(2)/s) are likely to be high-grade cancer foci compared with high ADC tumors (relative risk: 65.2). The sensitivity and specificity of the ADC value to predict high-grade cancer foci are 81.8 and 93.5 %, respectively. CONCLUSIONS: A low ADC value reflects the morphological and biological features of prostate cancer. Analyzing the ADC value may make it possible to more precisely predict the cancer aggressiveness of each focus before treatment.