Herein, we investigated possible practical issues for the smooth implementation of the revised Japanese Guidelines for Non-clinical Studies of Vaccines for the Prevention of Infectious Diseases, which were raised in response to public comments on the proposed guideline revision and a gap analysis of the World Health Organization and European Medicines Agency guidelines. We identified main issues such as the non-clinical safety studies of adjuvants and evaluation of local cumulative tolerance in toxicity studies. The revised Japanese Pharmaceuticals and Medical Devices Agency (PMDA)/Ministry of Health, Labour and Welfare (MHLW) guidelines require non-clinical safety studies for vaccines containing new adjuvants, but additional safety pharmacology studies or safety studies in two animal species may be required if non-clinical safety studies raise any concerns (i.e., systemic distribution). Adjuvant biodistribution studies may aid in understanding vaccine characteristics. The evaluation of local cumulative tolerance in non-clinical studies, which was the focus of the Japanese review, can be omitted by including a warning in the package insert to avoid injection to the same site. The study\'s findings will be reflected in a Q&A to be released by the Japanese MHLW. We hope that this study will contribute to the global and harmonized development of vaccines.

The success of the messenger RNA-based COVID-19 vaccines of Moderna and Pfizer/BioNTech marks the beginning of a new chapter in modern medicine. However, the rapid rise of mRNA therapeutics has resulted in a regulatory framework that is somewhat lagging. The current guidelines either do not apply, do not mention RNA therapeutics, or do not have widely accepted definitions. This review describes the guidelines for preclinical biodistribution studies of mRNA/siRNA therapeutics and highlights the relevant differences for mRNA vaccines. We also discuss the role of in vivo RNA imaging techniques and other assays to fulfill and/or complement the regulatory requirements. Specifically, quantitative whole-body autoradiography, microautoradiography, mass spectrometry-based assays, hybridization techniques (FISH, bDNA), PCR-based methods, in vivo fluorescence imaging, and in vivo bioluminescence imaging, are discussed. We conclude that this new and rapidly evolving class of medicines demands a multi-layered approach to fully understand its biodistribution and in vivo characteristics.

Existing and future nuclear fusion technologies involve the production and use of large quantities of tritium, a highly volatile, but low toxicity beta-emitting isotope of hydrogen. Tritium has received international attention because of public and scientific concerns over its release to the environment and the potential health impact of its internalization. This article provides a brief summary of the current state of knowledge of both the biological and regulatory aspects of tritium exposure; it also explores the gaps in this knowledge and provides recommendations on the best ways forward for improving our understanding of the health effects of low-level exposure to it. Linking health effects specifically to tritium exposure is challenging in epidemiological studies due to high uncertainty in tritium dosimetry and often suboptimal cohort sizes. We therefore argued that limits for tritium in drinking water should be based on evidence derived from controlled in vivo animal tritium toxicity studies that use realistically low levels of tritium. This article presents one such mouse study, undertaken within an international collaboration, and discusses the implications of its main findings, such as the similarity of the biokinetics of tritiated water (HTO) and organically bound tritium (OBT) and the higher biological effectiveness of OBT. This discussion is consistent with the position expressed in this article that in vivo animal tritium toxicity studies carried out within large, multi-partner collaborations allow evaluation of a great variety of health-related endpoints and essential to the development of international consensus on the regulation of tritium levels in the environment. Environ. Mol. Mutagen. 59:586-594, 2018. © 2018 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Nuclear medicine has a central role in the diagnosis, staging, response assessment and long-term follow-up of neuroblastoma, the most common solid extracranial tumour in children. These EANM guidelines include updated information on 123I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging with 18F-FDG, 18F-DOPA and 68Ga-DOTA peptides. These PET/CT studies are increasingly employed in clinical practice. Indications, advantages and limitations are presented along with recommendations on study protocols, interpretation of findings and reporting results.

Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using 68Ga-DOTA-conjugated peptides, as well as 18F-DOPA imaging for various neuroendocrine neoplasms.
The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with 68Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts.

OBJECTIVE: Obesity is a significant burden on the healthcare system in the United States, and determining the appropriate antimicrobial dosing regimen in morbidly obese patients is challenging. Morbidly obese patients have documented differences in pharmacokinetic and pharmacodynamic properties compared to normal-weight patients, which impact antibiotic efficacy and toxicity. The Food and Drug Administration does not recognize obesity as a special population and does not require pharmaceutical companies to perform studies specific to obese patients. However, there are an increasing number of post-approval studies in obese patients, and this manuscript reviews available clinical and pharmacokinetic literature regarding weight-based antimicrobial agents. Additionally, we describe a single-centre approach to optimize dosing in morbidly obese patients.
METHODS: A comprehensive literature search was performed on 15 weight-based antimicrobials in the setting of obesity: acyclovir, aminoglycosides, amphotericin B, cidofovir, colistimethate, daptomycin, flucytosine, foscarnet, ganciclovir, quinupristin/dalfopristin, trimethoprim/sulfamethoxazole, vancomycin and voriconazole. A weight-based antimicrobial dosing guideline for morbidly obese patients was developed. An analysis of guideline compliance and cost analysis were performed following guideline implementation.
CONCLUSIONS: This review describes the pharmacokinetic changes that occur in obese patients, including increased volume of distribution, altered hepatic metabolism, renal excretion and changes in protein binding. The majority of weight-based antimicrobials result in increased serum concentrations in morbidly obese patients compared to normal-weight patients when the calculated dose is based on actual body weight.
CONCLUSIONS: This review demonstrates different antibiotic pharmacokinetic properties are altered in obese patients that could impact efficacy and toxicity. A single-centre guideline for weight-based antimicrobial dosing in obesity was developed and provides recommendations for using ideal body weight, adjusted body weight or actual body weight when calculating antimicrobial doses. However, more research is needed to better elucidate optimal dosing of weight-based antimicrobials in obesity, with particular focus on efficacy and toxicity.

Among the prognostic factors when it comes to patients with high-grade gliomas, we find the radicality of the surgery performed. The limitations of this factor are caused by either the extension of the tumour or its location in an eloquent area. To achieve this goal, in the last few years we have developed several methods that allow us to maximise tumour resection, while always trying to cause the least possible co-morbidity. One of these methods includes the use of 5-amino-levulinic acid (5-ALA) and the development of fluorescence guided surgery. However, optimal performance requires knowledge of the product employed, the mode of administration and precautions to consider. Members of the neuro-oncology work group of the Spanish Neurosurgical Society (SENEC) have prepared this guideline or consensus document for anyone who wishes to become familiar with the use of 5-ALA fluorescence-guided surgery in the management of high-grade gliomas. For those who already utilise this technique, this document can be useful for consultation purposes.

The study aims to characterize the pharmacokinetic, tissue distribution, excretion, and antiviral activity properties of a novel pegylated recombinant human consensus interferon-α variant (PEG-IFN-SA) following a single subcutaneous administration to monkeys, rats and guinea pigs. Studies included: (1) pharmacokinetic properties of PEG-IFN-SA and comparison with those of non-pegylated IFN-SA in rhesus monkeys and rats; (2) tissue distribution and urinary, fecal, and biliary excretion patterns of (125)I-PEG-IFN-SA in guinea pigs; and (3) antiviral activity assessment of PEG-IFN-SA in cynomolgus monkeys. The pegylated protein exhibited improved pharmacokinetic properties compared to IFN-SA in both monkeys and rats, with a 12-fold and 15-fold increase in elimination half-life, and a 100-fold and 10-fold decrease in serum clearance, as well as a 2.5-fold and 10-fold increase in the time to reach peak serum concentration, respectively. (125)I-PEG-IFN-SA was found to be distributed to most of the tissues examined and has character of targeting special distribution, and urinary appeared to be a major route for the excretion of PEG-IFN-SA in guinea pigs. Serum sample analysis from PEG-IFN-SA-treated monkeys showed dose-dependent antiviral activity for one week. These findings demonstrate that pegylation of IFN-SA results in more desirable pharmacokinetic properties, enhanced drug exposure and sustained-efficacy of in vivo antiviral action.

This Note discusses the implications of a simple model for the thermal response of tissue subject to irradiation with millimeter waves (30-300 GHz) for setting limits for safe exposure to this energy. The estimated thresholds for thermal pain and thermal injury from long-term (minutes) and short-term (seconds) exposures are compared with two major exposure guidelines, IEEE C95.1-2005 and ICNIRP limits. An Appendix describes the rationale for setting the \"averaging times\" in IEEE C95.1-2005.

We describe here a protocol for labelling autologous white blood cells with (111)In-oxine based on previously published consensus papers and guidelines. This protocol includes quality control and safety procedures and is in accordance with current European Union regulations and International Atomic Energy Agency recommendations.