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 I-mIBG, the most common study in nuclear medicine for the evaluation of neuroblastoma, and on PET/CT imaging withF-FDG, F-DOPA andGa-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.

Highlights d Pathologic protein networks and their engagement in clinic are monitored by imaging d Real-time tumor pharmacometric data are obtained at the level of individual tumors d Theranostic and clinical assay combined provide quantitative tumor measurements d The platform provides dose and schedule information for epichaperome targeting

Background: To fulfil good manufacturing requirements, analytical methods for the analysis of pharmaceuticals for human and vetinary use must be validated. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) has published guidance documents on the requirements for such validation activities and these have been adopted by the European Medicines Agency, The U.S. Food and Drug Administration (FDA) and other regulatory bodies. These guidance documents do not, however, fully address all the specific tests required for the analysis of radiopharmaceuticals. This guideline attempts to rectify this shortcoming, by recommending approaches to validate such methods. Results: Recommedations for the validation of analytical methods which are specific for radiopharmaceutials are presented in this guideline, along with two practical examples. Conclusions: In order to comply with good manufacturing practice, analytical methods for radiopharmaceuticals for human use should be validated.

This guideline on current good radiopharmacy practice (cGRPP) for small-scale preparation of radiopharmaceuticals represents the view of the Radiopharmacy Committee of the European Association of Nuclear Medicine (EANM). The guideline is laid out in the format of the EU Good Manufacturing Practice (GMP) guidelines as defined in EudraLex volume 4. It is intended for non-commercial sites such as hospital radiopharmacies, nuclear medicine departments, research PET centres and in general any healthcare establishments. In the first section, general aspects which are applicable to all levels of operations are discussed. The second section discusses the preparation of small-scale radiopharmaceuticals (SSRP) using licensed generators and kits. Finally, the third section goes into the more complex preparation of SSRP from non-licensed starting materials, often requiring a purification step and sterile filtration. The intention is that the guideline will assist radiopharmacies in the preparation of diagnostic and therapeutic SSRP’s safe for human administration.

Tellurium dioxide / Iodine-124 / Dry distillation / PET Summary. Iodine-124 is a radionuclide with a 4.18 day halflife which decays by positron emission (23.3%) and electron capture (76.7 %). Details on the preparation of this radionuclide via the 124 Te(p,n) 124 I nuclear reaction are described. A reusable target uniquely suited for low energy cyclotron irradiations has been described along with specific characteristics for the dry distillation recovery of the 124 I species.

Purpose: 2-Nitro-α-[(2,2,2-trifluoroethoxy)methyl]-imidazole-1-ethanol (TF-MISO) was investigated as a potential noninvasive marker of tissue oxygen levels in tumors using 19F magnetic resonance spectroscopy (MRS) and 19F chemical shift imaging. Experimental Designs: In vitro data were obtained using high-performance liquid chromatography on tumor cells incubated under varying oxygen conditions to determine the oxygen-binding characteristics. In vivo data were obtained using a well-characterized hypoxic murine breast tumor (MCa), in addition to studies on a rat prostate tumor model (R3327-AT) implanted in nude mice. Detection of intratumor 19F signal from TF-MISO was done using MRS for up to 10 h following a 75 mg/kg i.v. injection. Localized distribution of the compound in the implanted MCa tumor has been imaged using slice-selective two-dimensional chemical shift imaging 6 h after injection. Results: The in vitro results showed that TF-MISO preferentially accumulates in cells incubated under anoxic conditions. The in vivo 19F MR spectral features (line width and chemical shift) were recorded as a function of time after injection, and the results indicate that the fluorine atoms are indeed sensitive to changes in the local environment while still providing a detectable MR signal. Ex vivo spectra were collected and established the visibility of the 19F signal under conditions of maximum hypoxia. Late time point (>6 h) tumor tissue concentrations, as obtained from 19F MRS, suggest that TF-MISO is reduced and retained in hypoxic tumor. The feasibility of obtaining TF-MISO tumor distribution maps in a reasonable time frame was established. Conclusions: Based on the results presented herein, it is suggested that TF-MISO has the potential to be a valid magnetic resonance hypoxia imaging reporter for both preclinical hypoxia studies and hypoxia-directed clinical therapy.

BackgroundValidation and qualification activities are nowadays an integral part of the day by day routine work in a radiopharmacy. This document is meant as an Appendix of Part B of the EANM “Guidelines on Good Radiopharmacy Practice (GRPP)” issued by the Radiopharmacy Committee of the EANM, covering the qualification and validation aspects related to the small-scale “in house” preparation of radiopharmaceuticals. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals which are not intended for commercial purposes or distribution.ResultsThe present guideline covers the validation and qualification activities following the well-known “validation chain”, that begins with editing the general Validation Master Plan document, includes all the required documentation (e.g. User Requirement Specification, Qualification protocols, etc.), and leads to the qualification of the equipment used in the preparation and quality control of radiopharmaceuticals, until the final step of Process Validation.ConclusionsA specific guidance to the qualification and validation activities specifically addressed to small-scale hospital/academia radiopharmacies is here provided. Additional information, including practical examples, are also available.Electronic supplementary materialThe online version of this article (doi:10.1186/s41181-017-0025-9) contains supplementary material, which is available to authorized users.

This document is meant to complement Part B of the EANM 'Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals' issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution.Keywords: radiopharmaceutical; positron emission tomography; single-photon emission computed tomography; process validation; automated radiosynthesis module Definitions (see also references 1 and 2) Radiopharmaceutical A radiopharmaceutical is any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. Small-scale radiopharmaceuticalA small-scale radiopharmaceutical is any in-house radiopharmaceutical not intended for commercial purposes or distribution, prepared on a small scale, excluding preparations based on licensed generators and labelling kits, and excluding preparation of kits. Finished productA finished product is a medicinal product that has undergone all stages of production, including packaging in its final container and labelling. PreparationPreparation includes all operations involved in the purchase of materials and products, production, QC, release and storage of a medicinal product and the related controls. Small-scale radiopharmacyA small-scale radiopharmacy is a facility where small-scale preparation of radiopharmaceuticals is carried out in accordance with national regulations for in-house use. The term small-scale radiopharmacy is not related to the physical size of the facility.