Manual on the proper use of the 211At-labeled PSMA ligand ([211At]PSMA-5) for clinical trials of targeted alpha therapy (1st edition)

The version of record of this article, first published in Annals of Nuclear Medicine, is available online at Publisher’s website: https://doi.org/10.1007/s12149-024-01916-6.Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients’ caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer

Reliability and Validity of Speech Evaluation in Adductor Spasmodic Dysphonia

Objectives. In order to establish a reliable diagnostic tool for adductor spasmodic dysphonia (ADSD), it is necessary to determine the proper terms representing its characteristic voice symptoms and to relate them to objective measures such as acoustic parameters or speech perturbation. The aim of this study was to evaluate speech in patients with ADSD by perceptual evaluations and acoustic measures, and to examine the reliability and validity of the measures by comparison with normal controls. Methods. Twenty-four patients with ADSD and 24 healthy volunteers matched to the ADSD patients with regard to age and sex participated in the study. Speech materials, consisting of three short sentences, were constructed from serial voiced syllables to elicit abductor voice breaks. Three otolaryngologists specializing in phoniatrics rated the degree of voice symptoms using a visual analog scale (VAS). VAS sheets with five 100-mm horizontal lines were given to each rater. The ends of the lines were labeled normal versus severe, and the five lines were labeled as overall severity and each of the four voice symptoms; strangulation, interruption, tremor and strained speech. Nine words were selected from the speech materials for acoustic analysis, and abnormal acoustic events were classified into one of the three categories; percentage of frequency shifts, percentage of aperiodic segments, or percentage of phonation breaks. Acoustic measures were performed by a speech-language-hearing therapist specializing in voice disorders and five healthy university students. To evaluate the intra- and inter-rater/measurer reliability of the VAS scores or acoustic measures, Pearson r correlations were calculated. To examine the validity of perceptual evaluations and acoustic measures, the sensitivity, specificity, positive predictive value and negative predictive value were calculated. Results. Pearson r correlation coefficients for overall severity showed the highest intra- and inter-rater reliability, and reliability coefficients for one of the four voice symptoms, strangulation (r = 0.816-0.937), were slightly higher than those for the other symptoms. For acoustic events, intra-measurer reliabilities were r = 0.645 (frequency shifts), r = 0.969 (aperiodic segments), and r = 1.0 (phonation breaks), and inter-measurer reliability ranged from r = 0.102 to r = 1.0 (average r = 0.861). The Pearson r correlation coefficient for phonation breaks was higher than those for the other acoustic events. Perceptual evaluation using VAS showed high sensitivity (91.7 %) and specificity (100 %), and acoustic analysis showed low sensitivity (70.8 %) and high specificity (100 %). Eight of the 24 patients were judged to be within normal limits by one or both evaluation methods. Conclusions. Both perceptual evaluation and acoustic measures alone were found to be likely to miss true ADSD patients. It is important to obtain a range of speech materials and to use a combination of perceptual evaluation and acoustic measures based on our understanding of the advantages and disadvantages of both methods

Botulinum Toxin Therapy: A Series of Clinical Studies on Patients with Spasmodic Dysphonia in Japan

Spasmodic dysphonia (SD) is a rare voice disorder caused by involuntary and intermittent spasms of the laryngeal muscles. Both diagnosis and treatment have been controversial. Therefore, a series of clinical studies has recently been conducted in Japan. A nationwide epidemiological survey revealed that adductor SD predominated (90–95% of all cases; 3.5–7.0/100,000), principally among young women in their 20s and 30s. To facilitate early diagnosis, we created diagnostic criteria for SD and a severity grading system. The diagnostic criteria include the principal and accompanying symptoms, clinical findings during phonation, the treatment response, and the differential diagnoses. The severity grade is determined using a combination of subjective and objective assessments. Botulinum toxin (BT) injection is the treatment of choice; however, there have been few high-quality clinical studies and BT has been used off-label. We conducted a placebo-controlled, randomized, double-blinded clinical trial of BT therapy; this was effective and safe. BT treatment is now funded by the Japanese medical insurance scheme. Studies thus far have facilitated early diagnosis and appropriate therapy; they have fostered patient awareness of SD