Comparative analysis of cancer cell responses to targeted radionuclide therapy (TRT) and external beam radiotherapy (EBRT)

The vast majority of our knowledge regarding cancer radiobiology and the activation of radioresistance mechanisms emerged from studies using external beam radiation therapy (EBRT). Yet, less is known about the cancer response to internal targeted radionuclide therapy (TRT). Our comparative phosphoproteomics analyzed cellular responses to TRT with lutetium-177-labeled minigastrin analogue [$^{177}$Lu]Lu-PP-F11N (β-emitter) and EBRT (ɣ-rays) in CCKBR-positive cancer cells. Activation of DNA damage response by p53 was induced by both types of radiotherapy, whereas TRT robustly increased activation of signaling pathways including epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs) or integrin receptor. Inhibition of EGFR or integrin signaling sensitized cancer cells to radiolabeled minigastrin. In vivo, EGFR inhibitor erlotinib increased therapeutic response to [$^{177}$Lu]Lu-PP-F11N and median survival of A431/CCKBR-tumor bearing nude mice. In summary, our study explores a complex scenario of cancer responses to different types of irradiation and pinpoints the radiosensitizing strategy, based on the targeting survival pathways, which are activated by TRT

EANM guideline on the validation of analytical methods for radiopharmaceuticals

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.</p

EANM guideline on the validation of analytical methods for radiopharmaceuticals

Contains fulltext : 219679.pdf (publisher's version ) (Open Access)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

EANM guideline on quality risk management for radiopharmaceuticals

This document is intended as a supplement to the EANM "Guidelines on current Good Radiopharmacy Practice (cGRPP)" issued by the Radiopharmacy Committee of the EANM (Gillings et al. in EJNMMI Radiopharm Chem. 6:8, 2021). The aim of the EANM Radiopharmacy Committee is to provide a document that describes how to manage risks associated with small-scale "in-house" preparation of radiopharmaceuticals, not intended for commercial purposes or distribution

Death and Science: The Existential Underpinnings of Belief in Intelligent Design and Discomfort with Evolution

The present research examined the psychological motives underlying widespread support for intelligent design theory (IDT), a purportedly scientific theory that lacks any scientific evidence; and antagonism toward evolutionary theory (ET), a theory supported by a large body of scientific evidence. We tested whether these attitudes are influenced by IDT's provision of an explanation of life's origins that better addresses existential concerns than ET. In four studies, existential threat (induced via reminders of participants' own mortality) increased acceptance of IDT and/or rejection of ET, regardless of participants' religion, religiosity, educational background, or preexisting attitude toward evolution. Effects were reversed by teaching participants that naturalism can be a source of existential meaning (Study 4), and among natural-science students for whom ET may already provide existential meaning (Study 5). These reversals suggest that the effect of heightened mortality awareness on attitudes toward ET and IDT is due to a desire to find greater meaning and purpose in science when existential threats are activated

Highlight selection of radiochemistry and radiopharmacy developments by editorial board (January-June 2020)

BackgroundThe Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field.ResultsThis commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.ConclusionTrends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry

Benthos

Currently, > 4,000 Arctic macro- and megabenthic species are known, representing the majority of Arctic marine faunal diversity. This estimate is expected to increase. • Benthic invertebrates are food to shes, marine mammals, seabirds and humans, and are commercially harvested. • Traditional Knowledge (TK) emphasizes the link between the benthic species and their predators, such as walrus, and their signi cance to culture. • Decadal changes in benthos biodiversity are observed in some well-studied regions, such as the Barents Sea and Chukchi Sea. • Drivers related to climate-change such as warming, ice decline and acidification are affecting the benthic community on a pan-Arctic scale, while drivers such as trawling, river/glacier discharge and invasive species have signficant impact on regional or local scales. • Increasing numbers of species are moving into, or shifting, their distributions in Arctic waters. These species will outcompete, prey on or offer less nutritious value as prey for Arctic species. • Current monitoring efforts have focused on macro- and megabenthic species, but have been confined to the Chukchi Sea and the Barents Sea. Efforts are increasing in waters of Greenland, Iceland, the Canadian Arctic, and in the Norwegian Sea. All other Arctic Marine Areas are lacking long-term benthic monitoring. • As a first step towards an international collaborative monitoring framework, we recommend to develop a time- and cost-effective, long-term and standardized monitoring of megabenthic communities in all Arctic regions with regular annual groundfish assessment surveys. Expanding monitoring on micro-, meio- and macrobenthic groups is encouraged

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

BackgroundThe Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development.ResultsThis commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.ConclusionTrends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry

Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

Contains fulltext : 88022.pdf (publisher's version ) (Closed access)PURPOSE: In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. METHODS: Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of (111)In-albumin, (111)In-minigastrin, (111)In-exendin and (111)In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of (111)In-minigastrin, (111)In-exendin and (111)In-octreotide was determined. RESULTS: FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of (111)In-albumin, (111)In-exendin and (111)In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide #6), was selected for in vivo testing. In rats, 5 mg of peptide #6 very efficiently inhibited the renal uptake of (111)In-minigastrin, by 88%. Uptake of (111)In-exendin and (111)In-octreotide was reduced by 26 and 33%, respectively. CONCLUSIONS: The albumin-derived peptide #6 efficiently inhibited the renal reabsorption of (111)In-minigastrin, (111)In-exendin and (111)In-octreotide and is a promising candidate for kidney protection in PRRT.1 februari 201

Highlight selection of radiochemistry and radiopharmacy developments by editorial board (January-June 2020)

BackgroundThe Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to describe trends in the field.ResultsThis commentary of highlights has resulted in 19 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.ConclusionTrends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.</p