Artificial neural network (ANN)-based bone scan index (BSI), a marker of the amount of bone metastasis, has been shown to enhance diagnostic accuracy and reproducibility but is potentially affected by training databases. The aims of this study were to revise the software using a large number of Japanese databases and to validate its diagnostic accuracy compared with the original Swedish training database.

Objective: In this phase II study, we aimed to investigate the efficacy and safety of single-dose [¹³¹I]meta-iodobenzylguanidine (¹³¹I-mIBG) therapy in patients with refractory pheochromocytoma and paraganglioma (PPGL). Patients and methods: This study was designed as an open-label, single-arm, multi-center, phase II clinical trial. The enrolled patients were administered 7.4 GBq of ¹³¹I-mIBG. Its efficacy was evaluated 12 and 24 weeks later, and its safety was monitored continuously until the end of the study. We evaluated the biochemical response rate as the primary endpoint using the one-sided exact binomial test based on the null hypothesis (≤ 5%). Results: Seventeen patients were enrolled in this study, of which 16 were treated. The biochemical response rate (≥ 50% decrease in urinary catecholamines) was 23.5% (90% confidence interval: 8.5–46.1%, p = 0.009). The radiographic response rates, determined with CT/MRI according to the response evaluation criteria in solid tumors (RECIST) version 1.1 and ¹²³I-mIBG scintigraphy were 5.9% (0.3%–25.0%) and 29.4% (12.4%–52.2%), respectively. The most frequent non-hematologic treatment-emergent adverse events (TEAEs) were gastrointestinal symptoms including nausea, appetite loss, and constipation, which were, together, observed in 15 of 16 patients. Hematologic TEAEs up to grade 3 were observed in 14 of 16 patients. No grade 4 or higher TEAEs were observed. All patients had experienced at least one TEAE, but no fatal or irreversible TEAEs were observed. Conclusion: A single dose ¹³¹I-mIBG therapy was well tolerated by patients with PPGL, and statistically significantly reduced catecholamine levels compared to the threshold response rate, which may lead to an improved prognosis for these patients.

Refractory pheochromocytoma and paraganglioma (PPGL) have a poor prognosis and the treatment strategy remains to be established. This multi-institutional phase I study was performed to determine the safety, dose-limiting toxicity (DLT), and efficacy of [¹³¹I]-meta-iodobenzylguanidine (¹³¹I-mIBG) therapy for refractory PPGLs. Twenty patients with refractory PPGL were enrolled in this study. We administered fixed doses of ¹³¹I-mIBG to all patients, delivering a second and third course of ¹³¹I-mIBG to eight and three patients, respectively. During the 20 weeks after ¹³¹I-mIBG injection, the authors surveyed the adverse events in accordance with the Common Terminology Criteria for Adverse Events. All patients experienced adverse events and adverse reactions, but none experienced a grade 4 adverse event. Twelve weeks after ¹³¹I-mIBG injection, examinations for the evaluation of therapeutic effects was performed in accordance with the Response Evaluation Criteria in Solid Tumours (RECIST). The best overall response rates (based on RECIST categories) were 10% (complete response), 65% (stable disease), 15% (progressive disease), and 10% (not all evaluated). The efficacy and safety of ¹³¹I-mIBG therapy was shown in patients with refractory PPGL, and DLT was observed in neither single nor repeated ¹³¹I-mIBG therapy, indicating a tolerability for ¹³¹I-mIBG therapy.

Detecting culprit coronary arteries in patients with ischemia using only myocardial perfusion single-photon emission computed tomography (SPECT) can be challenging. This study aimed to improve the detection of culprit regions using an artificial neural network (ANN) to analyze hybrid images of coronary computed tomography angiography (CCTA) and myocardial perfusion SPECT. This study enrolled 59 patients with stable coronary artery disease (CAD) who had been assessed by coronary angiography within 60 days of myocardial perfusion SPECT. Two nuclear medicine physicians interpreted the myocardial perfusion SPECT and hybrid images with four grades of confidence, then drew regions on polar maps to identify culprit coronary arteries. The gold standard was determined by the consensus of two other nuclear cardiology specialist based on coronary angiography findings and clinical information. The ability to detect culprit coronary arteries was compared among experienced nuclear cardiologists and the ANN. Receiver operating characteristics (ROC) curves were analyzed and areas under the ROC curves (AUC) were determined. Using hybrid images, observer A detected CAD in the right (RCA), left anterior descending (LAD), and left circumflex (LCX) coronary arteries with 83.6%, 89.3%, and 94.4% accuracy, respectively and observer B did so with 72.9%, 84.2%, and 89.3%, respectively. The ANN was 79.1%, 89.8%, and 89.3% accurate for each coronary artery. Diagnostic accuracy was comparable between the ANN and experienced nuclear medicine physicians. The AUC was significantly improved using hybrid images in the RCA region (observer A: from 0.715 to 0.835, p = 0.0031; observer B: from 0.771 to 0.843, p = 0.042). To detect culprit coronary arteries in perfusion defects of the inferior wall without using hybrid images was problematic because the perfused areas of the LCX and RCA varied among individuals. Hybrid images of CCTA and myocardial perfusion SPECT are useful for detecting culprit coronary arteries. Diagnoses using artificial intelligence are comparable to that by nuclear medicine physicians.

DNA double-strand breaks (DSBs) are considered the most relevant lesions to the DNA damage of ionizing radiation (IR), and γ-H2AX foci in peripheral blood lymphocytes are regarded as an adequate marker for DSB quantitative studies. This study aimed to investigate IR-induced DNA damage in mice through γ-H2AX fluorescence analyses by flow cytometry (FCM). The levels of γ-H2AX in CD4/CD8/B220-positive lymphocytes were quantified by FCM through mean fluorescence intensity (MFI) values. Peripheral venous blood samples were collected for evaluation, and all the control groups were restrained from irradiation. For external irradiation experiments, the dose-dependency of MFI values and temporal alternations were assessed both in vitro and in vivo. External radiation exposure damage was positively correlated with the absorbed radiation dose, and the lymphocyte recovered from damage within 3 days. I-131 sodium iodide solution (74 MBq) was injected into the mice intraperitoneally for internal irradiation experiments. Gamma counting and γH2AX foci analyses were performed at 1 h and 24 h by the group. The blood-to-blood S values (S_{blood←blood}) were applied for the blood-absorbed dose estimation. Internal low-dose-irradiation-induced damage was proved to recover within 24 h. The FCM method was found to be an effective way of quantitatively assessing IR-induced DNA damage.