Ein. Tierethik Vor der Durchführung der langen Dauer Hyperthermie an Mäusen stellen Sie sicher, dass das Verfahren durch Institutional Animal Care und Use Committee genehmigt wurde. Alle Verfahren in diesem Papier diskutiert und gezeigt im zugehörigen Video wurden von der Institutional Animal Ethics Committee des National Institute of Immunology zugelassen. 2. Understanding Hyperthermie Ganzkörperhyperthermie (WBH) durch Anordnen der Tiere in Käfigen, die in vorgewärmtem Inkubator gehalten sind bei 39,5 ° C gegeben gelieferte Während der Standardisierung von Protokoll wurde ein Temperatursensor chirurgisch in den Mäusen implantiert und ihre Körpertemperatur wurde in verschiedenen experimentellen Bedingungen überwacht. Es wurde beobachtet, dass beim Platzieren der Tiere im erwärmten Umgebung, deren Temperatur allmählich von 37 ° C auf bis zu 42 ° C über die Dauer von 100 min (Abbildung 1). The resultierende &quot;spike&quot; in der Temperatur ist faszinierend, wie die interne Körpertemperatur erschossen sogar noch höher als der äußere Umgebungstemperatur. Wenn der Körper 40 ° C überschritten, würde das Tier Anzeichen von Stress und Dehydratisierung wie Benetzungsmittel um die Schnauze. Erhöhen Sie die Körpertemperatur über 40 ° C, wird die Benetzung und irreversible Stress oder sogar zum Tod der Tiere aufgrund der Hitze Stress führen. Deshalb ist es wichtig, um die Temperaturspitzen während des Verlaufs der Hyperthermie zu verhindern. Dieses Phänomen der Hochtemperatur-Spikes wird mit der physikalischen Hyperaktivität Tier während Hyperthermie Exposition verbunden. Ähnliche Temperaturspitzen wurden von anderen Gruppen zu und beobachtet mit dem physischen Hyperaktivität des Tieres auf, die die Umwelt mit höheren Temperaturen 10 eingeführt verbunden. In unserem Protokoll werden die Mäuse während der Hyperthermie Exposition immobilisiert. Alsin 2 dargestellt, verhindert Immobilisierung Tier die Temperaturspitzen. Wir haben 8-12 Wochen alte BALB / Cj Mäusen zur Demonstration dieses Protokoll verwendet. Das Protokoll ist nicht auf einen bestimmten Typ / Stamm der Mäuse beschränkt. 3. Vorbereitung für die Experiment 3,1 Incubator Dieses Experiment kann in einem normalen CO 2-Inkubator durchgeführt werden, da sie eine gute Temperaturkontrolle aufweisen. Trennen CO 2-Gas-und Wasser entfernen hält Tablett mit dem CO 2-Inkubator. In einigen Modellen von Inkubatoren ist es möglich, Abschalten des CO 2-Controller. Vereinbaren Regalen des Inkubators, so dass ein Mäusen Käfig bequem innerhalb platziert werden konnte. Stellen Sie die Temperatur des Inkubators bei 39,5 ° C. 3,2 Cages Typischerweise wird die Hyperthermie Experiment 4 Mäusen zu einer Zeit durchgeführt wird. Zwei Käfige sind erforderlich; aufe wird im Inkubator platziert und der andere ist außerhalb bei Raumtemperatur vorgelegt. Einstreu der Käfige wird vermieden, da die Pflaster Bettausstattungen nass mit Zeit, die in ungleichmäßige Temperaturverteilung innerhalb des Käfigs ergibt geworden. Die Außenseite Käfig sollte Futterpellets und Wasserflasche. 3,3 Mice Immobilisierung Rohren Im Verlauf der ersten vier Zyklen von Hyperthermie Mäuse werden in perforierten Röhren immobilisiert. Diese Immobilisierung Rohre von 50 ml &#39;Zentrifuge&#39; Röhren durch piercing 3 mm Löchern ganzen Körper und vier solcher Rohre benötigt werden vorgenommen werden. Die 50ml Tube bequem immobilisieren BALB / Cj Mäuse, die älter als 8 Wochen sind. Rohre der geeigneten Größen können für einige ungewöhnlich unterschiedlichen Stamm von Mäusen oder Mäusen, die sehr jung oder älter als 50 Wochen sind erforderlich. Ort Immobilisierung Rohren und einem Käfig im Inneren des Inkubator bei 39,5 ° C gehalten wird Warten für mindestens 2 Stunden, so dass der Käfig und immobilization Rohren erreicht die Temperatur des Inkubators. 4. Ersten Zyklus der Hyperthermie Mäuse können Dehydratation während der Belichtung Hyperthermie erleben. Daher sollten Sie vor Beginn des Experiments, verwalten 0,5 ml Kochsalzlösung intraperitoneal jeder Maus. Verwenden Sie eine 26 G Nadel mit 1 ml Spritze. Schnell nehmen Sie den Käfig in den Inkubator gestellt, Ort ein Tier in jeder Immobilisierung Rohre und platzieren Sie den Käfig zurück in den Inkubator. Notieren Sie sich die Zeit. Es ist wesentlich, um den Käfig an der gleichen Stelle in den Inkubator jedes Mal zu halten. Nach 90 min, nehmen Sie den Käfig aus dem Inkubator. Lassen Sie Tiere aus den Immobilisierung Rohre und legen Sie sie in den Käfig bei normaler Temperatur mit einfachem Zugang zu Nahrung und Wasser. Leeren Immobilisierung Röhrchen wieder in den Inkubator. Nach 15 min wird die zweite Zyklus von Hyperthermie durch Abgabe 0 gestartet.5 ml Kochsalzlösung intraperitoneal an jeder Maus. Anschließend werden sie in 50 ml perforierten Rohren Immobilisierung immobilisiert und in den Inkubator. 5. Nachfolgende Hyperthermie Cycles Für ersten vier Zyklen, ist es wesentlich, an Mäuse während der Belichtung und Hyperthermie in den ersten zwei Zyklen immobilisieren, wird Kochsalzinjektion vor Beginn der Hyperthermie Periode. Nachdem diese Zyklen von Hyperthermie durch Rest folgte abgeschlossen sind, erhalten Mäusen akklimatisieren und werden nicht während der Hyperthermie Exposition hyperaktiv. Die intraperitoneale Injektion von Kochsalzlösung kann nicht notwendig sein, wenn Mäuse problemlos auf Nahrung und Wasser während der Ruhezeit. 6. Nach all den Zyklen abgeschlossen, ist der letzte Schritt, um die Tiere zu untersuchen Es sollte keine Tod während der Hyperthermie-Zyklen. Jedes Tier hat sehr sorgfältig in der ersten beobachtet werdenpaar Zyklen. Schnell für jede Benetzung der ganzen Schnauze aussehen. Dieses Symptom ist eine Signatur der Austrocknung. Mäuse mit solchen Symptomen sollten sofort 0,5 ml Kochsalzlösung ip und Ruhe bei Raumtemperatur gegeben werden. Die meisten der immobilisierten Mäuse benötigen keine zusätzliche Pflege und erfolgreich tragen die Belastung die Hyperthermie. Nach Abschluss der erforderlichen Zyklen, können die Tiere schwach aussehen und dehydriert, aber sie werden schnell innerhalb von wenigen Stunden zu erholen. <img src="/files/ftp_upload/3801/3801fig1.jpg" alt="Abbildung 1" /> Abbildung 1. Variation der Körperkerntemperatur Mäuse, wenn der Käfig in einem Inkubator wurde bei 39,5 ° C platziert Nach 90 min wurde der Käfig aus dem Inkubator entnommen und bei 25 ° C. Rote Kreise weisen auf hohe Temperaturspitzen. <img src="/files/ftp_upload/3801/3801fig2.jpg" alt="Abbildung 2" /> Abbildung 2. Variation des Kernkörpers Temwieder eines immobilisierten Mäuse während der Hyperthermie-Zyklen. Nach Immobilisierung des Tieres wurden hohe Temperaturen Spikes nicht beachten, wenn der Käfig bei 39,5 ° C platziert wurde

<ol>
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Wir haben nichts zu offenbaren.

<html> So weit zurück wie 5000 v. Chr. behandelt ägyptischen Ärzte Tumoren mit Wärme. Die Griechen erkannten den Wert der Wärme in einigen medizinischen Behandlungen. Die ältesten Texte des Gesetzes des Mose erwähnt heißen Quellen (Genesis 36:24), um therapeutisch erhöhen die Körpertemperatur. Die früheren Techniken verwendet entweder die Verwendung von pyrogenen mikrobiellen Extrakten für die Induktion von Fieber oder heißem Wasser Bäder für die Induktion von Hyperthermie <sup...

<table border="1"><tr><td></td><td></td><td></td><td></td></tr><tr><td> Thermistor </td><td> RS Components </td><td> 528-8558 </td><td></td></tr><tr><td> CO 2 Inkubator </td><td> Heraeus </td><td> B5060 EK-CO2 </td><td></td></tr><tr><td> Mäuse Käfige </td><td> Citizen Industries Ltd. </td><td></td><td> Typ B 365X207X190 cm </td></tr><tr><td> Tierfutter </td><td> Provimi India </td><td></td><td></td></tr><tr><td> Wasserflasche für Käfig </td><td> Lokale Lieferanten </td><td></td><td> Glasflasche </td></tr><tr><td> Lötkolben </td><td> Solderon, Indien </td><td></td><td></td></tr><tr><td> 50 ml Zentrifugenröhrchen </td><td> BD Biosciences </td><td> 352070 </td><td></td></tr><tr><td> Timer </td><td> Lokale Lieferanten </td><td></td><td></td></tr><tr><td> 1 ml Spritze mit 26G Nadel </td><td> BD Biosciences </td><td> 309602 </td><td></td></tr><tr><td> Salzhaltig </td><td> Lokale Lieferanten </td><td></td><td></td></tr></table>

protocol for long duration whole body hyperthermia in mice

Hyperthermie ist ein allgemeiner Begriff verwendet, um den Anstieg der Körperkerntemperatur über normal zu definieren. Es wird oft verwendet, um die erhöhte Körpertemperatur, die während Fieber beobachtet wird beschreiben. Der Einsatz von Hyperthermie als Adjuvans wurde als vielversprechendes Verfahren für Tumorregression im Bereich der Krebsbiologie entstanden. Zu diesem Zweck ist die wichtigste Anforderung, zuverlässige und gleichmäßige Erwärmung Protokolle haben. Wir haben ein Protokoll zur Hyperthermie (Ganzkörper) in Mäusen entwickelt. In diesem Protokoll werden die Tiere um Zyklen der Hyperthermie für 90 min mit einer Pause von 15 min, gefolgt ausgesetzt. Während dieser Zeit Mäusen haben leichten Zugang zu Nahrung und Wasser. Hohe Körpertemperatur Spikes in den Mäusen während der ersten paar Hyperthermie Exposition Zyklen werden durch Immobilisierung des Tieres verhindert. Zusätzlich wird in normaler Kochsalzlösung ersten Zyklen verabreicht werden, um die Wirkungen von Dehydratisierung zu minimieren. Dieses Protokoll kann simuliert Fieber ähnlichen Bedingungen bei Mäusen bis zu 12-24 Stunden. Wir habenverwendet 8-12 Wochen alte BALB / Cj weiblichen Mäusen, um das Protokoll zu demonstrieren.

Watch this Scientific Journal Video about Protocol for Long Duration Whole Body Hyperthermia in Mice at JoVE.com

Protocol for Long Duration Whole Body Hyperthermia in Mice

Dieser Beitrag beschreibt ein Protokoll für die Ganzkörper-Hyperthermie bei Mäusen, die Fieber ähnlichen Bedingungen zu stimulieren bis zu 12-24 Stunden kann.

Protokoll für Long Duration Ganzkörper-Hyperthermie in Mäuse

Hyperthermia is a general term used to define the increase in core body temperature above normal. It is often used to describe the increased core body ...

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Research

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Medicine

11.5K Aufrufe.  National Institute of Immunology. Dieser Beitrag beschreibt ein Protokoll für die Ganzkörper-Hyperthermie bei Mäusen, die Fieber ähnlichen Bedingungen zu stimulieren bis zu 12-24 Stunden kann.

Serie: Protocol for Long Duration Whole Body Hyperthermia in Mice

Protocols for Assessing Radiofrequency Interactions with Gold Nanoparticles and Biological Systems for Non-invasive Hyperthermia Cancer Therapy

Cancer therapies which are less toxic and invasive than their existing counterparts are highly desirable. The use of RF electric-fields that penetrate deep into the body, causing minimal toxicity, are currently being studied as a viable means of non-invasive cancer therapy. It is envisioned that the interactions of RF energy with internalized nanoparticles (NPs) can liberate heat which can then cause overheating (hyperthermia) of the cell, ultimately ending in cell necrosis.
In the case of non-biological systems, we present detailed protocols relating to quantifying the heat liberated by highly-concentrated NP colloids. For biological systems, in the case of in vitro experiments, we describe the techniques and conditions which must be adhered to in order to effectively expose cancer cells to RF energy without bulk media heating artifacts significantly obscuring the data. Finally, we give a detailed methodology for in vivo mouse models with ectopic hepatic cancer tumors.

We describe the protocols used to investigate the interactions of 13.56 MHz radiofrequency (RF) electric-fields with gold nanoparticle colloids in both non-biological and biological systems (in vitro/vivo). These interactions are being investigated for applications in cancer therapy.

Protokolle für die Beurteilung der Radiofrequenz-Wechselwirkungen mit Gold-Nanopartikel und biologische Systeme für die Nicht-invasive Krebstherapie Hyperthermie

Cancer therapies  which are less toxic and invasive than their existing counterparts are highly  desirable. The use of RF electric-fields that penetrate ...

Forschung

Medizin

Parabiosis in Mice: A Detailed Protocol

Parabiosis is a surgical union of two organisms allowing sharing of the blood circulation. Attaching the skin of two animals promotes formation of microvasculature at the site of inflammation. Parabiotic partners share their circulating antigens and thus are free of adverse immune reaction. First described by Paul Bert in 18641, the parabiosis surgery was refined by Bunster and Meyer in 1933 to improve animal survival2. In the current protocol, two mice are surgically joined following a modification of the Bunster and Meyer technique. Animals are connected through the elbow and knee joints followed by attachment of the skin allowing firm support that prevents strain on the sutured skin. Herein, we describe in detail the parabiotic joining of a ubiquitous GFP expressing mouse to a wild type (WT) mouse. Two weeks after the procedure, the pair is separated and GFP positive cells can be detected by flow cytometric analysis in the blood circulation of the WT mouse. The blood chimerism allows one to examine the contribution of the circulating cells from one animal in the other.

Parabiotic joining of two organisms leads to the development of a shared circulatory system. In this protocol, we describe the surgical steps to form a parabiotic connection between a wild-type mouse and a constitutive GFP-expressing mouse.

Parabiose in Mäuse: Ein detailliertes Protokoll

Parabiosis is a surgical union of two organisms allowing sharing of the blood circulation. Attaching the skin of two animals promotes formation of ...

Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study model. As the use of mouse models are often a vital step in preclinical drug discovery and drug development1-8, it is necessary to design a system to introduce drugs into mice in a uniform, reproducible manner. Ideally, the system should permit the collection of blood samples at regular intervals over a set time course. The ability to measure drug concentrations by mass-spectrometry, has allowed investigators to follow the changes in plasma drug levels over time in individual mice1, 9, 10. In this study, paclitaxel was introduced into transgenic mice as a continuous arterial infusion over three hours, while blood samples were simultaneously taken by retro-orbital bleeds at set time points. Carotid artery infusions are a potential alternative to jugular vein infusions, when factors such as mammary tumors or other obstructions make jugular infusions impractical. Using this technique, paclitaxel concentrations in plasma and tissue achieved similar levels as compared to jugular infusion. In this tutorial, we will demonstrate how to successfully catheterize the carotid artery by preparing an optimized catheter for the individual mouse model, then show how to insert and secure the catheter into the mouse carotid artery, thread the end of the catheter out through the back of the mouse&#8217;s neck, and hook the mouse to a pump to deliver a controlled rate of drug influx. Multiple low volume retro-orbital bleeds allow for analysis of plasma drug concentrations over time.

This method was developed with the goal of delivering a steady drug solution via the carotid artery, to assess the pharmacokinetics of novel drugs in mouse models.

Halsschlagader Infusionen für pharmakokinetischen und pharmakodynamischen Analyse von Taxanen in Mäusen

When proposing the use of a drug, drug combination, or drug delivery into a novel system, one must assess the pharmacokinetics of the drug in the study ...

Long-term Blood Pressure Measurement in Freely Moving Mice Using Telemetry

During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. Indeed, research focusing on the discovery of new potential therapeutic targets using genetically altered mice requires a reliable, long-term assessment of the systemic arterial pressure variation. Currently, the gold standard for obtaining long-term measurements of blood pressure in ambulatory mice uses implantable radio-transmitters, which require&#160;artery cannulation. This technique eliminates the need for tethering, restraining, or anesthetizing the animals which introduce stress and artifacts during data sampling. However, arterial blood pressure monitoring in mice via catheterization can be rather challenging due to the small size of the arteries. Here we present a step-by-step guide to illustrate the crucial key passages for a successful subcutaneous implantation of radio-transmitters and carotid artery cannulation in mice. We also include examples of long-term blood pressure activity taken from freely moving mice after a period of post-surgery recovery. Following this procedure will allow reliable direct blood pressure recordings from multiple animals simultaneously.

The goal of this protocol is to assess systemic blood pressure in conscious freely moving mice using implantable radio-telemetry devices.

Langzeit-Blutdruckmessung in sich frei bewegenden Mäuse Telemetrie

During the development of new vasoactive agents, arterial blood pressure monitoring is crucial for evaluating the efficacy of the new proposed drugs. ...

Body Composition and Metabolic Caging Analysis in High Fat Fed Mice

Alterations to body composition (fat or lean mass), metabolic parameters such as whole-body oxygen consumption, energy expenditure, and substrate utilization, and behaviors such as food intake and physical activity can provide important information regarding the underlying mechanisms of disease. Given the importance of body composition and metabolism to the development of obesity and its subsequent sequelae, it is necessary to make accurate measures of these parameters in the pre-clinical research setting. Advances in technology over the past few decades have made it possible to derive these measures in rodent models in a non-invasive and longitudinal fashion. Consequently, these metabolic measures have proven useful when assessing the response of genetic manipulations (for example knockout or transgenic mice, viral knock-down or overexpression of genes), experimental drug/compound screening and dietary, behavioral or physical activity interventions. Herein, we describe the protocols used to measure body composition and metabolic parameters using an animal monitoring system in chow-fed and high fat diet-fed mice.

This protocol describes the use of a body composition analyzer and metabolic animal monitoring system to characterize body composition and metabolic parameters in mice. An obesity model induced by high-fat feeding is used as an example for the application of these techniques.

Körperzusammensetzung und festsetzende Stoffwechselanalyse bei hohen Fett Fed Mäusen

Alterations to body composition (fat or lean mass), metabolic parameters such as whole-body oxygen consumption, energy expenditure, and substrate ...

Protocol to Create Chronic Wounds in Diabetic Mice

Chronic wounds develop as a result of defective regulation in one or more complex cellular and molecular processes involved in proper healing. They impact ~6.5M people and cost ~$40B/year in the US alone. Although a significant effort has been invested in understanding how chronic wounds develop in humans, fundamental questions remain unanswered. Recently, we developed a novel mouse model for diabetic chronic wounds that have many characteristics of human chronic wounds. Using db/db-/- mice, we can generate chronic wounds by inducing high levels of oxidative stress (OS) in the wound tissue immediately after wounding, using a one-time treatment with inhibitors specific to the antioxidant enzymes catalase and glutathione peroxidase. These wounds have high levels of OS, develop biofilm naturally, become fully chronic within 20 days after treatment and can remain open more for more than 60 days. This novel model has many features of diabetic chronic wounds in humans and therefore can contribute significantly to advancing fundamental understanding of how wounds become chronic. This is a major breakthrough because chronic wounds in humans cause significant pain and distress to patients and result in amputation if unresolved. Moreover, these wounds are very expensive and time-consuming to treat, and lead to significant loss of personal income to patients. Advancements in this field of study through the use of our chronic wound model can significantly improve health care for millions who suffer under this debilitating condition. In this protocol, we describe in great detail the procedure to cause acute wounds to become chronic, which has not been done before.

Chronic wounds are developed from acute wounds on a diabetic mouse model by inducing high levels of oxidative stress after a full-thickness cutaneous wound. The wound is treated with inhibitors for catalase and glutathione peroxidase, resulting in impaired healing and biofilm development by bacteria present in the skin microbiome.

Protokoll zur Herstellung chronischer Wunden bei diabetischen Mäusen

Chronic wounds develop as a result of defective regulation in one or more complex cellular and molecular processes involved in proper healing. They impact ...

Handheld Metal Detector Screening for Metallic Foreign Body Ingestion in Children

Coins are the most common ingested metallic foreign bodies among children. The goal of this protocol is to assess the accuracy and feasibility of using a handheld metal detector to detect ingested metallic foreign bodies in children. We propose that by introducing handheld metal detector screening early in the triage process of children with high suspicion of metallic foreign body ingestion, the number of radiographs being ordered to localize the metallic foreign body can be reduced in this radio-sensitive population. The study protocol requires the screening of the participants for history of foreign body ingestion and exclusion of patients with respiratory distress or metallic implants. The patient changes to hospital gown and items that could contain metal like eyeglasses, earrings, pendants, and ornaments are removed. The patient is positioned in the center of the room away from other metallic interferences. The working status of the handheld metal detector is first confirmed by eliciting a positive audio-visual signal. Then the screening is done in an erect position with head in extension to expose the neck, from the level of the chin to the level of the hip joint, to cover the anatomical areas from neck to pelvis in a zig-zag manner both anteriorly and posteriorly. A positive audio-visual signal is carefully noted during the scanning for the presence of metallic foreign body. Relevant radiographs are ordered as per the area detected on the metal detector screening. The handheld metal detector was able to precisely identify all the coins among the ingested metallic foreign bodies in our study. The handheld metal detector could not consistently detect non-coin metallic foreign bodies. This protocol demonstrates the accuracy of handheld metal detector in the identification and localization of coins and coin like metallic foreign bodies.

Here, we present a protocol to use the handheld metal detector, to screen for the presence of ingested metallic foreign bodies in children who present to the pediatric emergency medicine department with a history of foreign body ingestion.

Handheld-Metalldetektor-Screening für metallische Fremdkörper Verschlucken bei Kindern

Coins are the most common ingested metallic foreign bodies among children. The goal of this protocol is to assess the accuracy and feasibility of using a ...

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT&#39;s ability to expend energy has made it a potential target for novel therapies to ameliorate obesity and associated metabolic disorders in humans. Though this tissue has been well studied in small animals, BAT&#39;s thermogenic capacity in humans remains largely unknown due to the difficulties of measuring its volume, activity, and distribution. Identifying and quantifying active human BAT is commonly performed using 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography (PET/CT) scans following cold-exposure or pharmacological activation. Here we describe a detailed image-analysis approach to quantify total-body human BAT from 18F-FDG PET/CT scans using an open-source software. We demonstrate the drawing of user-specified regions of interest to identify metabolically active adipose tissue while avoiding common non-BAT tissues, to measure BAT volume and activity, and to further characterize its anatomical distribution. Although this rigorous approach is time-consuming, we believe it will ultimately provide a foundation to develop future automated BAT quantification algorithms.

Whole Body and Regional Quantification of Active Human Brown Adipose Tissue Using 18F-FDG PET/CT

Using free, open-source software, we have developed an analytical approach to quantify total and regional brown adipose tissue (BAT) volume and metabolic activity of BAT using 18F-FDG PET/CT.

Ganzen Körper und regionale Quantifizierung der aktiven Menschen braune Fettgewebe mit 18F-FDG PET/CT

In endothermic animals, brown adipose tissue (BAT) is activated to produce heat for defending body temperature in response to cold. BAT&#39;s ability to ...

A Whole Body Dosimetry Protocol for Peptide-Receptor Radionuclide Therapy (PRRT): 2D Planar Image and Hybrid 2D+3D SPECT/CT Image Methods

Peptide-receptor-radionuclide-therapy (PPRT) is a targeted therapy that combines a short-range energy radionuclide with a substrate with high specificity for cancer cell receptors. After injection, the radiotracer is distributed throughout the entire body, with a higher uptake in tissues where targeted receptors are overexpressed. The use of beta/gamma radionuclide emitters enables therapy imaging (beta-emission) and post-therapy imaging (gamma-emission) to be performed at the same time. Post-treatment sequential images permit absorbed dose calculation based on local uptake and wash-in/wash-out kinetics. We implemented a hybrid method that combines information derived from both 2D and 3D images. Serial whole-body images and blood samples are acquired to estimate the absorbed dose to different organs at risk and to lesions disseminated throughout the body. A single 3D-SPECT/CT image, limited to the abdominal region, overcomes projection overlap on planar images of different structures such as the intestines and kidneys. The hybrid 2D+3D-SPECT/CT method combines the effective half-life information derived from 2D planar images with the local uptake distribution derived from 3D images. We implemented this methodology to estimate the absorbed dose for patients undergoing PRRT with 177Lu-PSMA-617. The methodology could, however, be implemented with other beta-gamma radiotracers. To date, 10 patients have been enrolled into the dosimetry study with 177Lu-PSMA-617 combined with drug protectors for kidneys and salivary glands (mannitol and glutamate tablets, respectively). The median ratio between kidney uptake at 24 h evaluated on planar images and 3D-SPECT/CT is 0.45 (range:0.32-1.23). The comparison between hybrid and full 3D approach has been tested on one patient, resulting in a 1.6% underestimation with respect to full 3D (2D: 0.829 mGy/MBq, hybrid: 0.315 mGy/MBq, 3D: 0.320 mGy/MBq). Treatment safety has been confirmed, with a mean absorbed dose of 0.73 mGy/MBq (range:0.26-1.07) for kidneys, 0.56 mGy/MBq (0.33-2.63) for the parotid glands and 0.63 mGy/MBq (0.23-1.20) for submandibular glands, values in accordance with previously published data.

A Whole Body Dosimetry Protocol for Peptide-Receptor Radionuclide Therapy PRRT: 2D Planar Image and Hybrid 2D+3D SPECT/CT Image Methods

This method estimates the absorbed dose of different structures for peptide-receptor-radionuclide-therapy (PRRT) with the possibility of avoiding organ overlap on 2D-projections. Serial whole-body planar images permit estimation of mean absorbed doses along the whole body, while the hybrid approach, combining planar images and 3D-SPECT/CT image, overcomes the limitations of structure overlapping.

A Whole Body Dosimetrie Protocol for Peptide-Receptor Radionuclide Therapy (PRRT): 2D Planar Image and Hybrid 2D+3D SPECT/CT Image Methods

Peptide-receptor-radionuclide-therapy (PPRT) is a targeted therapy that combines a short-range energy radionuclide with a substrate with high specificity ...

Assessing Whole-Body Lipid-Handling Capacity in Mice

Assessing lipid metabolism is a cornerstone of evaluating metabolic function, and it is considered essential for in vivo metabolism studies. Lipids are a class of many different molecules with many pathways involved in their synthesis and metabolism. A starting point for evaluating lipid hemostasis for nutrition and obesity research is needed. This paper describes three easy and accessible methods that require little expertise or practice to master, and that can be adapted by most labs to screen for lipid-metabolism abnormalities in mice. These methods are (1) measuring several fasting serum lipid molecules using commercial kits (2) assaying for dietary lipid-handling capability through an oral intralipid tolerance test, and (3) evaluating the response to a pharmaceutical compound, CL 316,243, in mice. Together, these methods will provide a high-level overview of lipid handling capability in mice.

This paper provides three easy and accessible assays for assessing lipid metabolism in mice.

Beurteilung der Ganzkörper-Lipid-Handling-Kapazität bei Mäusen

Assessing lipid metabolism is a cornerstone of evaluating metabolic function, and it is considered essential for in vivo metabolism studies. Lipids are a ...