Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

Diagnosis of skull-base invasion by nasopharyngeal tumors on CT with a deep-learning approach.

PURPOSE: To develop a convolutional neural network (CNN) model to diagnose skull-base invasion by nasopharyngeal malignancies in CT images and evaluate the model's diagnostic performance. MATERIALS AND METHODS: We divided 100 malignant nasopharyngeal tumor lesions into a training (n = 70) and a test (n = 30) dataset. Two head/neck radiologists reviewed CT and MRI images and determined the positive/negative skull-base invasion status of each case (training dataset: 29 invasion-positive and 41 invasion-negative; test dataset: 13 invasion-positive and 17 invasion-negative). Preprocessing involved extracting continuous slices of the nasopharynx and clivus. The preprocessed training dataset was used for transfer learning with Residual Neural Networks 50 to create a diagnostic CNN model, which was then tested on the preprocessed test dataset to determine the invasion status and model performance. Original CT images from the test dataset were reviewed by a radiologist with extensive head/neck imaging experience (senior reader: SR) and another less-experienced radiologist (junior reader: JR). Gradient-weighted class activation maps (Grad-CAMs) were created to visualize the explainability of the invasion status classification. RESULTS: The CNN model's diagnostic accuracy was 0.973, significantly higher than those of the two radiologists (SR: 0.838; JR: 0.595). Receiver operating characteristic curve analysis gave an area under the curve of 0.953 for the CNN model (versus 0.832 and 0.617 for SR and JR; both p < 0.05). The Grad-CAMs suggested that the invasion-negative cases were present predominantly in bone marrow, while the invasion-positive cases exhibited osteosclerosis and nasopharyngeal masses. CONCLUSIONS: This CNN technique would be useful for CT-based diagnosis of skull-base invasion by nasopharyngeal malignancies.

Comparative study of physiological FDG uptake in small structures between silicon photomultiplier-based PET and conventional PET.

OBJECTIVE: Silicon photomultiplier-based positron emission tomography/computed tomography (SiPM-PET/CT) has the superior spatial resolution to conventional PET/CT (cPET/CT). This head-to-head comparison study compared the images of physiological 18F-fluorodeoxyglucose (FDG) accumulation in small-volume structures between SiPM-PET/CT and cPET/CT in patients scanned with both modalities, and we investigated whether the thresholds that are reported to be useful for differentiating physiological accumulations from malignant lesions can also be applied to SiPM-PET/CT. METHODS: We enrolled 21 consecutive patients with head and neck malignancies who underwent whole-body FDG-PET/CT for initial staging or a follow-up evaluation (October 2020 to March 2022). After being injected with FDG, all patients underwent PET acquisition on both Vereos PET-CT and Gemini TF64 PET-CT systems (both Philips Healthcare) in random order. For each patient, the maximum standardized uptake value (SUVmax) was measured in the pituitary gland, esophagogastric junction (EGJ), adrenal glands, lumbar enlargement of the spinal cord, and epididymis. We measured the liver SUVmean and the blood pool SUVmean to calculate the target-to-liver ratio (TLR) and the target-to-blood ratio (TBR), respectively. Between-groups differences in each variable were examined by a paired t-test. We also investigated whether there were cases of target uptake greater than the reported threshold for distinguishing pathological from physiological accumulations. RESULTS: Data were available for 19 patients. Ten patients were in Group 1, i.e., the patients who underwent SiPM-PET first, and the remaining nine patients who underwent cPET first were in Group 2. In the SiPM-PET results, the SUVmax of all targets was significantly higher than that obtained by cPET in all patients, and this tendency was also observed when the patients were divided into Groups 1/2. The TLRs of all targets were significantly higher in SiPM-PET than in cPET in all patients, and SiPM-PET also showed significantly higher TBRs for all targets except the EGJ (p = 0.052). CONCLUSIONS: The physiological uptake in the small structures studied herein showed high accumulation on SiPM-PET. Our results also suggest that the thresholds reported for cPET to distinguish pathological accumulations likely lead to false-positive findings in SIPM-PET evaluations.

Predictive factors of early FDG-PET response to [131I] MIBG treatment for unresectable or metastatic pheochromocytomas and paragangliomas (PPGLs).

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that produce catecholamines. [131I] MIBG-avid unresectable or metastatic PPGLs are treated with [131I] MIBG therapy. A high metabolic tumour volume (MTV) and total lesion glycolysis (TLG) can be poor prognostic factors. Therefore, we evaluated the metabolic responses to [131I] MIBG therapy with respect to other clinical factors.A retrospective study was performed on a series of 20 patients who underwent FDG-PET before and after [131I] MIBG therapy. We administered a single dose comprising 5.5 GBq of [131I] MIBG. Semi-quantitative parameters (SUVmax, MTV, and TLG) were calculated using the liver SUV (mean + 3SD) as a threshold on Metavol software. The semi-quantitative FDG-PET parameters for determining response were complete response , partial remission, stable disease, and progressive disease (PD). We divided our study participants into the PD and non-PD groups and compared the overall survival between the two groups. Subsequently, we evaluated the relationships between metabolic response and age, sex, tumour type, metastatic site, chemotherapy or external radiation history, and 24-hour urine catecholamine levels by univariate logistic regression analyses. Both MTV-based and TLG-based criteria for PD vs. non-PD were significant prognostic factors (p = 0.014). However, treatment response as evaluated based on the SUVmax was not a significant predictor. Higher urinary dopamine levels were associated with poor metabolic response as assessed by MTV and TLG. The other clinical parameters were non-significant. Poor metabolic response (measured with MTV and TLG) to [131I] MIBG therapy in unresectable or metastatic PPGLs was related to shorter OS. The poor metabolic response can be predicted using the urinary dopamine level.

Correlations between Photovoltaic Characteristics, Adsorption Number, and Regeneration Kinetics in Dye-Sensitized Solar Cells Revealed by Scanning Photocurrent Microscopy.

Newly developed simultaneous scanning photocurrent and luminescence microscopy was applied to ruthenium-based dye-sensitized solar cells (DSCs) comprising a cover glass photoanode with a 100 nm thick TiO2 layer. Using this, we have investigated the lateral variations of several parameters of these DSCs under short-circuit conditions. Simultaneous measurement of photocurrent and luminescence images for the same area of the DSC demonstrated submicrometric lateral resolution of our photocurrent microscopy, which is approximately 10 times better than the resolution of photocurrent microscopy used in past studies. The photovoltaic parameters, such as short-circuit current density, open-circuit voltage, and charge-collection efficiency, were thus evaluated for local (or submicrometric) regions of the DSCs. Furthermore, the photocurrent saturation behavior of the DSCs was examined as a function of the excitation rate and analyzed on the basis of a three-state kinetic model. This protocol allowed for quantification of the dye-adsorption number and dye-regeneration rate constant for any local area of the DSCs. Consequently, the correlations between the dye adsorption number, photovoltaic parameters, and regeneration rate constant, which are difficult to address through examination of the entire cell, were revealed by the "zoom-in" approach utilizing this high-resolution photocurrent microscopy.