Name: a basic positron emission tomography system constructed to locate a radioactive source in a bi-dimensional space
Uploaded: 2016-02-01T13:00:00.000+00:00
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Description: Watch this Scientific Journal Video about A Basic Positron Emission Tomography System Constructed to Locate a Radioactive Source in a Bi-dimensional Space at JoVE.com

We are very grateful for the financial support of the Physics Department of CINVESTAV. We also want to thank our technician Marcos Fontaine Sanchez for his remarkable assistance with the set up. Thanks a lot to Sarah LaPointe for reviewing the English-language of this document.

1. Preparation of the PET Setup
<ol>
	<li>Prepare the PMT&#39;s coupled with plastic scintillator pieces. Depending on the kind of PMT (size, shape of the photocathode) build an adequate scintillator piece to fit with the photocathode of the PMT.
	<ol>
		<li>Wrap the scintillator pieces with black tape. Leave one side uncovered, as it will be coupled with the PMT light entrance. 
		NOTE: It is important that these pieces are previously polished to avoid light accumulation losses.</li>
	</ol>
	</li>
	<li>Clean the PMT light entrance with alcohol (commercial alcohol concentration of 70%) then apply optical grease to it and the scintillator&#39;s uncovered face. Coupled the PMT face with the scintillator and wrap them with more black tape.
	<ol>
		<li>Connect the PMT to the source voltage (a cable is included for every PMT, in this case bias 14 V bias and 0.5 V for voltage control). Identify the signals coming from the PMT by connecting the PMT signal cable to a standard digital oscilloscope channel (a signal cable is also included for every PMT). Observe the variations in amplitude of the signals when turning on/off the light in the lab, to verify there are no light losses. Repeat this step for each of the four detectors, where a detector means scintillator plus PMT.</li>
	</ol>
	</li>
	<li>Build a coincidence system by placing the scintillator part of one detector above the corresponding part of another detector. Put two NIM (Nuclear Instrument Module) instruments called discriminator and logic unit modules in a NIM crate.</li>
	<li>Connect the output signals from the detectors to the inputs of a discriminator module. Use a logic unit in the AND mode, by selecting this logic case in the logic unit front panel. Connect the two discriminator outputs in the logic unit inputs. 
	NOTE: AND is a logical operation that selects when two square signals arrive at the same time or in coincidence.</li>
	<li>Connect the logic unit output signal in a scaler module (which counts digital signals) to count the events (created by the cosmic rays hitting in coincidence both detectors).</li>
</ol>
2. Acquiring Signals with PET
<ol>
	<li>Place both detectors in the opposite corners of the square area defined before, so they face each other, and are 20 cm apart, and do the same exercise as 1.4 and 1.5, but this time, instead of using cosmic rays (cosmic rays served as a provisional natural radioactive source), use the Na-22 radiation source.
	<ol>
		<li>Place the radioactive source in a middle distance between both detectors and make data acquisition through the scaler module. The system set up and the schematic arrangement of the logic block used to obtain a coincidence can be seen in Figures 1, 2, and 3.</li>
	</ol>
	</li>
	<li>Measure the time difference of the arriving signals by connecting the two discriminate PMT&#39;s outputs and the coincidence output in the oscilloscope. Each of the three signals goes to an oscilloscope input; there will be three square signals in the oscilloscope screen. With the horizontal scale (time scale) measure the time difference of the two discriminate signals. 
	NOTE: When the radioactive source is directly in the middle between both detectors there will be little or no separation or time difference between the square discriminate signals on average, and when the radioactive source is out of the center and close to one of the PMT then there will be time difference on average.</li>
	<li>Send these timing signals to one of the eight channels of the CAMAC (Computer Automated Measurement And Control) TDC (Time to Digital Converter) module. To do this, connect the output of logic AND to the TDC input call &#34;START&#34; then connect the detector discriminate outputs to the TDC inputs which are called &#34;STOP&#34;. The AND signal has to be delayed through a Delay Module by some nanoseconds in order for this signal to arrive before the other two STOP signals (see Figure 4).</li>
	<li>Calibrate the TDC counting units vs. time showed by the oscilloscope through a software program (see steps in Section 3). Do this calibration by using the distance separation between the radioactive source and one of the detectors, measuring the average time difference (step 2.3) of every position. Establish a software communication between the different modules and the computer via a standard bus GPIB (General Purpose Instrumentation Bus) to do this calibration.</li>
</ol>
3. Building the Virtual Instrument Interface
<ol>
	<li>Download and use a LabView software or any similar software. 
	NOTE: To work with Labview, it is necessary to have some knowledge of the &#34;G programming language&#34;. In this language, no code has to be written, and all the actions performed can be done from a software tool palette. An easy guide with practical examples can be found in the help tool.</li>
	<li>Select the array utility from the front panel tool palette (programming variables containers) to save the TDC output data. 
	NOTE: The &#34;front panel&#34; is the graphic interface of the virtual instrument to the user and the &#34;block diagram&#34; is used for software programming.</li>
	<li>Plot the data acquisition (time data from TDC) by selecting a logic instrument from the plots menu. Identify the plots data related with every position of the source. Do this by varying the source distance from the detectors line by some centimeters.</li>
	<li>Take the mean of the data using the statistical functions (mean) from the mathematical menu tool, and choose an interval of values centered in the mean. Then, according to the programming logic followed, use the necessary tools from the array menu to remove all data with values outside this interval.</li>
	<li>Select indicators from the block diagram tool palette to show the number of data stored in each array and identify a few containers with the largest number of data stored.</li>
	<li>Get the mean of the data in each array selected in the step 3.5 and use this information to establish a set of time intervals values for each source position using for this the LabView block diagram tool palette.</li>
	<li>Select an array of indicators from the front panel tool palette to store the mean obtained in step 3.6 for a sequence of measurements.</li>
	<li>Select a case structure from the block diagram tool palette to relate each position with its respective interval from step 3.7, and associate each interval to one virtual LED in an array from the front panel tool palette.</li>
	<li>Notice the time each signal takes to arrive to the TDC channels: when the radioactive source is moved from the middle closer to one detector, observe a movement of the virtual source in the programming array of LEDs (see Figure 5) moving to the right in the computer.</li>
	<li>Include a control (variable programming element) from the front panel tool palette for the total time acquisition. 
	NOTE: The efficiency of the positioning will depend on this control time tool: the more time the acquisition takes, the more precisely the virtual object simulating the radioactive source will give the correct position.</li>
</ol>
4. Graphical Results
<ol>
	<li>For calibration purposes, place the source at any intermediate position relative to one of the coupled pairs of detectors. Take measurements for 30 min, and with the data acquired, take the average of the values accumulated every 2 min. Repeat this process for different source positions and plot the average value from each detector in all positions (see Figures 6 and 7). The differences of the detectors values are plotted in Figure 8.</li>
	<li>To obtain better results, select two detectors having similar data values to form a couple. To test this, put the PMT control voltage to its lower value, in this case 0.5 V. Start measuring the number of detected events with the scaler module for a fixed time by connecting the detector output to the scaler input. Increase the voltage by 0.01 V and measure again. Repeat this process to reach the maximum possible control value, in this case 0.9 V.
	<ol>
		<li>Plot the number of detected events versus the control voltage in semi logarithmic scales (see Figure 9). Couple the pairs of detectors having similar distributions.</li>
	</ol>
	</li>
	<li>To test the sensitivity of the system, place the radioactive source in some equal spacing intermediate positions along the lines, in this case there are five. Acquire data for 5 min in each position, and plot the mean and median of the values obtained for each detector independently (see Figures 10 and 11).</li>
</ol>

<ol>
	<li>Cerello, P., Pennazio, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+innovative+detector+concept+for+hybrid+4D-PET/MRI.">An innovative detector concept for hybrid 4D-PET/MRI.</a> Imaging. Nucl. Instr. Meth. Phys. Res. 702, 1-3 (2013).</li><li>Muehllerher, G., Karp, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Positron+tomography+emission.">Positron tomography emission.</a> Phys. Med. Biol. 51, R117-R137 (2006).</li><li>Conti, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=State+of+the+art+and+challenges+of+time+of+flight+PET.">State of the art and challenges of time of flight PET.</a> Physica Medica. 25 (1), 1-11 (2008).</li><li>Abreu, Y., Pi&#241;era, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simulation+of+a+PET+system+and+study+of+some+geometry+parameters.">Simulation of a PET system and study of some geometry parameters.</a> AIP conference. 1032, 219-221 (2008).</li><li>Langner, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Development of a parallel Computing optimized head movement correction method in PET. , (2003).</li><li>Budinger, T. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time-of-flight+PET.">Time-of-flight PET.</a> J. Nucl Med. 28 (3), 73-78 (1983).</li><li>Leo, W. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Techniques for Nuclear and Particle Physics Experiments. , (1987).</li><li>Budinger, T. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Instrumentation+trends+in+nuclear+medicine.">Instrumentation trends in nuclear medicine.</a> Semin Nucl Med. 7 (4), 285-297 (1977).</li><li>Burnham, C., Bradshaw, J., Kaufmann, D., Chesler, D., Browner, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Positron+tomography+employing+a+one+dimension+BGO+scintillation+camera.">A Positron tomography employing a one dimension BGO scintillation camera.</a> IEEE Trans. Nucl. Sci. 30 (1), 661-664 (1983).</li><li>Burnham, C., Bradshaw, J., Kaufmann, D., Chesler, D., Steams, C. W., Browner, G. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+of+a+cylindrical+shape+scintillation+camera+for+positron+tomographs.">Design of a cylindrical shape scintillation camera for positron tomographs.</a> IEEE Trans. Nucl. Sci. 32 (1), 889-893 (1985).</li></ol>

There are no competing financial interests.

One important aspect of this system is to have a very good control over spatial and time resolutions. The spatial resolution of PET is limited by the physical characteristics of the radioactive decay and the annihilation, but also by technical aspects of the coincidence registration (steps 1.1 and 1.2) and by external sources of errors, such as object movement during the examination5. Thus, the exact position measured will depend on the TOF difference (step 2.4). One technique to achieve a good time resolution...

Positron Emission Tomography is a non-invasive imaging technique used for obtaining digital images of the inner tissues and organs of the body. Various non-invasive techniques exist that allow one to obtain images and information on the internal workings of a patient such as Computer Axial Tomography (TAC) and Magnetic Resonance Imaging (MRI). Both give good spatial resolution and are additionally used for applications in anatomic and physiologic studies. Although comparatively PET gives less spatial resolution, it provides more information concerning the metabolism occurring in the zone of interest. PET is widely used to obtain functional and morphological information; its main clinical applications are in the fields of oncology, neurology and cardiology. Also, PET images can help physicians give better diagnoses, e.g., establish tumor treatment planning.
The basic working principle of PET systems is the detection of two photons or gamma rays coming from a positron-electron annihilation pair, both flying in opposite directions towards the detectors, which commonly consist of scintillator crystals coupled with PMTs. The scintillator crystals transform gamma radiation into visible light, which travels to a PMT which converts the light signal to an electrical pulse via a photoelectric process. Inside the PMT electronic devices called dynodes are present, which increase the magnitude of the electrical charge before sending it to a read-out system. These two detected photons were created when a positron (positively charged electron) emitted by an isotope fluid, which was injected into the bloodstream of the body, annihilates with an electron in the body. The read-out system measures in coincidence the arrival time of the two back-to-back photons with respect to a time reference and further it substrates both times to obtain the difference. The system uses this time difference to calculate the space position where the radiation source emitted both photons, and thus where the electron-positron annihilation occurred.
Some features of PET systems must be defined to optimize the quality of the image and to increase spatial and time resolution. One feature to consider is the Line of Response (LOR), defined as the distance that the two photons travel after the annihilation process. Another feature to consider is the Time of Flight (TOF). The quality of the images also depends on external features, mainly the bodily organs and the patient&#39;s movements during the treatment session1. The isotopes used in PET systems are called Beta+ emitters. These isotopes have a short half-life (on the order of seconds). They are produced in particles accelerators (cyclotrons) when stable elements are bombarded with protons or deuterons causing nuclear reactions. Such reactions transform the stable elements into unstable isotopes, such as C-11, N-13, O-15, F-18 among others2.
There are two types of PET. (1) Conventional: this uses the TOF information only to identify the line along which the annihilation occurred, but it is unable to determine the origin place of the two photons. It requires additional analytical or iterative reconstruction algorithms to estimate this. (2) TOF PET: utilizes the TOF difference to locate the annihilation position of the emitted positron. The time resolution is used in the reconstruction algorithm as a kernel for a localization probability function3.
Our main objective is to demonstrate the primary functions of PET, which is used to locate a radiation source in space. The principal scope of the PET system set proposed here is to provide a basic PET construction guide for the academic public, and to explain, in a simple way, its main properties.

<table><tbody><tr><td>Low threshold Discriminator</td><td>CAEN</td><td>N845</td><td></td></tr><tr><td>Logic Units</td><td>Lecroy</td><td>365AL</td><td></td></tr><tr><td>Time delay</td><td>CAEN</td><td>N108A</td><td></td></tr><tr><td>Oscilloscope</td><td>Tektronic</td><td>TDS3014C</td><td></td></tr><tr><td>Quad Scaler and preset counter</td><td>CAEN</td><td>N1145</td><td></td></tr><tr><td>TDC</td><td>Lecroy</td><td>2228</td><td></td></tr><tr><td>PMT&amp;rsquo;s</td><td>Hamamatsu</td><td>H5783p</td><td></td></tr><tr><td>Power Chasis</td><td>Lecroy</td><td>1403</td><td></td></tr><tr><td>GPIB Interface</td><td>Lecroy</td><td>8901A</td><td></td></tr><tr><td>NIM Power Supply</td><td>Lecroy</td><td>1002B</td><td></td></tr><tr><td>CAMAC Crate</td><td>Borer-co</td><td>1902A</td><td></td></tr><tr><td>Scintillator Crystals</td><td>Bicron</td><td>408</td><td>1 cm x 2 cm x 5 cm</td></tr><tr><td>Power Supply</td><td>Agilent</td><td>E3631</td><td></td></tr><tr><td>Na 22 Radioactive Source</td><td></td><td></td><td>activity 2&amp;nbsp;&amp;mu;Ci</td></tr><tr><td>Software LabView 7.1</td><td>National intruments</td><td></td><td></td></tr><tr><td>lemo cables connectors</td><td></td><td></td><td>2&amp;nbsp;nsec, 3&amp;nbsp;nsec and 8&amp;nbsp;nsec</td></tr><tr><td>isolator film</td><td></td><td></td><td></td></tr></tbody></table>

a basic positron emission tomography system constructed to locate a radioactive source in a bi-dimensional space

A simple Positron Emission Tomography (PET) prototype has been constructed to fully characterize its basic working principles. The PET prototype was created by coupling plastic scintillator crystals to photomultipliers or PMT&#39;s which are placed at opposing positions to detect two gamma rays emitted from a radioactive source, of which is placed in the geometric center of the PET set-up. The prototype consists of four detectors placed geometrically in a 20 cm diameter circle, and a radioactive source in the center. By moving the radioactive source centimeters from the center the system one is able to detect the displacement by measuring the time of flight difference between any two PMT&#39;s and, with this information, the system can calculate the virtual position in a graphical interface. In this way, the prototype reproduces the main principles of a PET system. It is capable to determine the real position of the source with intervals of 4 cm in 2 lines of detection taking less than 2 min.

Two main results are achieved with this PET system. First: an efficient synchronization between visual effects of the virtual radioactive source when moving the real radioactive sample. With this program, users have control of the acquisition time, the number of repetitions in the same position, the variation of the interval around the acquisition data mean, among others. Second: the construction of a simple structure of coincidence logic to obtain the time difference between two signals,...

Watch this Scientific Journal Video about A Basic Positron Emission Tomography System Constructed to Locate a Radioactive Source in a Bi-dimensional Space at JoVE.com

A Basic Positron Emission Tomography System Constructed to Locate a Radioactive Source in a Bi-dimensional Space

We present a simple but well-constructed Positron Emission Tomography (PET) system and elucidate its basic working principles. The goal of this protocol is to guide the user in constructing and testing a simple PET system.

A simple Positron Emission Tomography (PET) prototype has been constructed to fully characterize its basic working principles. The PET prototype was ...

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Research

JoVE Journal

Engineering

8.5K Views.  Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav). We present a simple but well-constructed Positron Emission Tomography (PET) system and elucidate its basic working principles. The goal of this protocol is to guide the user in constructing and testing a simple PET system.

Video: A Basic Positron Emission Tomography System Constructed to Locate a Radioactive Source in a Bi-dimensional Space

PET and MRI Guided Irradiation of a Glioblastoma Rat Model Using a Micro-irradiator

For decades, small animal radiation research was mostly performed using fairly crude experimental setups applying simple single-beam techniques without the ability to target a specific or well-delineated tumor volume. The delivery of radiation was achieved using fixed radiation sources or linear accelerators producing megavoltage (MV) X-rays. These devices are unable to achieve sub-millimeter precision required for small animals. Furthermore, the high doses delivered to healthy surrounding tissue hamper response assessment. To increase the translation between small animal studies and humans, our goal was to mimic the treatment of human glioblastoma in a rat model. To enable a more accurate irradiation in a preclinical setting, recently, precision image-guided small animal radiation research platforms were developed. Similar to human planning systems, treatment planning on these micro-irradiators is based on computed tomography (CT). However, low soft-tissue contrast on CT makes it very challenging to localize targets in certain tissues, such as the brain. Therefore, incorporating magnetic resonance imaging (MRI), which has excellent soft-tissue contrast compared to CT, would enable a more precise delineation of the target for irradiation. In the last decade also biological imaging techniques, such as positron emission tomography (PET) gained interest for radiation therapy treatment guidance. PET enables the visualization of e.g., glucose consumption, amino-acid transport, or hypoxia, present in the tumor. Targeting those highly proliferative or radio-resistant parts of the tumor with a higher dose could give a survival benefit. This hypothesis led to the introduction of the biological tumor volume (BTV), besides the conventional gross target volume (GTV), clinical target volume (CTV), and planned target volume (PTV).
At the preclinical imaging lab of Ghent University, a micro-irradiator, a small animal PET, and a 7 T small animal MRI are available. The goal was to incorporate MRI-guided irradiation and PET-guided sub-volume boosting in a glioblastoma rat model.

In the past, small animal irradiation was usually performed without the ability to target a well-delineated tumor volume. The goal was to mimic the treatment of human glioblastoma in rats. Using a small animal irradiation platform, we performed MRI-guided 3D conformal irradiation with PET-based sub-volume boosting in a preclinical setting.

For decades, small animal radiation research was mostly performed using fairly crude experimental setups applying simple single-beam techniques without ...

Cancer Research

Visualization of Low-Level Gamma Radiation Sources Using a Low-Cost, High-Sensitivity, Omnidirectional Compton Camera

We present experimental protocols for visualizing various low-level gamma radiation sources in the ambient environment. Experiments were conducted by using a low-cost, high-sensitivity, omnidirectional, gamma-ray imaging Compton camera. In the laboratory, the position of a sub-MeV gamma radiation source such as 137Cs can easily be monitored via omnidirectional gamma-ray imaging obtained by the Compton camera. In contrast, a stationary, wall-mounted dose rate monitor cannot always successfully monitor such a source. Furthermore, we successfully demonstrated the possibility of visualizing the radioactivity movement in the environment, for example, the movement of a patient injected with 18F-fluorodeoxyglucose (18F-FDG) in a nuclear medicine facility. In the Fukushima field, we easily obtained omnidirectional gamma-ray images concerned with the distribution on the ground of low-level radioactive contamination by radioactive cesium released by the Fukushima Daiichi nuclear power plant accident in 2011. We demonstrate clear advantages of using our procedure with this camera to visualize gamma-ray sources. Our protocols can further be used to discover low-level gamma radiation sources, in place of stationary dose rate monitors and/or portable survey meters used conventionally.

We present experimental protocols for visualizing various low-level gamma radiation sources in the ambient environment using a low-cost, high-sensitivity, omnidirectional, gamma-ray imaging Compton camera.

We present experimental protocols for visualizing various low-level gamma radiation sources in the ambient environment. Experiments were conducted by ...

Environment

Positron Emission Tomography-based Dose Painting Radiation Therapy in a Glioblastoma Rat Model using the Small Animal Radiation Research Platform

A rat glioblastoma model to mimic chemo-radiation treatment of human glioblastoma in the clinic was previously established. Similar to the clinical treatment, computed tomography (CT) and magnetic resonance imaging (MRI) were combined during the treatment-planning process. Positron emission tomography (PET) imaging was subsequently added to implement sub-volume boosting using a micro-irradiation system. However, combining three imaging modalities (CT, MRI, and PET) using a micro-irradiation system proved to be labor-intensive because multimodal imaging, treatment planning, and dose delivery have to be completed sequentially in the preclinical setting. This also results in a workflow that is more prone to human error. Therefore, a user-friendly algorithm to further optimize preclinical multimodal imaging-based radiation treatment planning was implemented. This software tool was used to evaluate the accuracy and efficiency of dose painting radiation therapy with micro-irradiation by using an in silico study design. The new methodology for dose painting radiation therapy is superior to the previously described method in terms of accuracy, time efficiency, and intra- and inter-user variability. It is also an important step towards the implementation of inverse treatment planning on micro-irradiators, where forward planning is still commonly used, in contrast to clinical systems.

Here we present a protocol to perform preclinical positron emission tomography-based radiotherapy in a rat glioblastoma model using algorithms developed in-house to optimize the accuracy and efficiency.

A rat glioblastoma model to mimic chemo-radiation treatment of human glioblastoma in the clinic was previously established. Similar to the clinical ...

Automation of a Positron-emission Tomography (PET) Radiotracer Synthesis Protocol for Clinical Production

The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological targets and processes. However, the increasing number of different tracers creates challenges for their production at radiopharmacies. While historically it has been practical to dedicate a custom-configured radiosynthesizer and hot cell for the repeated production of each individual tracer, it is becoming necessary to change this workflow. Recent commercial radiosynthesizers based on disposable cassettes/kits for each tracer simplify the production of multiple tracers with one set of equipment by eliminating the need for custom tracer-specific modifications. Furthermore, some of these radiosynthesizers enable the operator to develop and optimize their own synthesis protocols in addition to purchasing commercially-available kits. In this protocol, we describe the general procedure for how the manual synthesis of a new PET tracer can be automated on one of these radiosynthesizers and validated for the production of clinical-grade tracers. As an example, we use the ELIXYS radiosynthesizer, a flexible cassette-based radiochemistry tool that can support both PET tracer development efforts, as well as routine clinical probe manufacturing on the same system, to produce [18F]Clofarabine ([18F]CFA), a PET tracer to measure in vivo deoxycytidine kinase (dCK) enzyme activity. Translating a manual synthesis involves breaking down the synthetic protocol into basic radiochemistry processes that are then translated into intuitive chemistry &#34;unit operations&#34; supported by the synthesizer software. These operations can then rapidly be converted into an automated synthesis program by assembling them using the drag-and-drop interface. After basic testing, the synthesis and purification procedure may require optimization to achieve the desired yield and purity. Once the desired performance is achieved, a validation of the synthesis is carried out to determine its suitability for the production of the radiotracer for clinical use.

Automation of a Positron-emission Tomography PET Radiotracer Synthesis Protocol for Clinical Production

Positron-emission tomography (PET) imaging sites that are involved in multiple early clinical research trials need robust and versatile radiotracer manufacturing capabilities. Using the radiotracer [18F]Clofarabine as an example, we illustrate how to automate the synthesis of a radiotracer using a flexible, cassette-based radiosynthesizer and validate the synthesis for clinical use.

The development of new positron-emission tomography (PET) tracers is enabling researchers and clinicians to image an increasingly wide array of biological ...

Chemistry

Radiosynthesis and PET/CT Imaging of 68Ga-Labelled Nanobody in Xenograft Models

Radiosynthesis, Quality Control, and Small Animal Positron Emission Tomography Imaging of 68Ga-Labelled Nano Molecules

Small animal Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging techniques are crucial in preclinical cancer research, necessitating meticulous attention to radiotracer synthesis, quality assurance, and in vivo injection protocols. This study presents a comprehensive workflow tailored to enhance the robustness and reproducibility of small animal PET experiments. The synthesis process in the radiochemistry laboratory using 68Ga is detailed, highlighting stringent quality control and assurance protocols for each radiotracer production. Parameters such as concentration, molar activity, pH, and purity are rigorously monitored, aligning with standards applicable to human studies. This methodology introduces streamlined syringe preparation and a custom-designed 30G cannula for precise intravenous injections into mice. Monitoring of animal health during scanning, including temperature and heart rate, ensures their well-being throughout the procedure. Dosages for PET and SPECT scans are predetermined to balance data acquisition with minimizing radiation exposure to animals and researchers. Similarly, CT scans employ pre-programmed settings to limit radiation exposure, especially pertinent in long-term studies assessing treatment effects. By optimizing these steps, the workflow aims to standardize procedures, reduce variability, and enhance the quality of small animal PET/SPECT/CT imaging. This resource provides valuable insights for researchers seeking to improve the accuracy and reliability of preclinical investigations in molecular imaging, ultimately advancing the field.

This paper describes the radiosynthesis, formulation, quality control of a new radiolabeled probe (i.e., 68Ga-labeled nanobody NM-02), and its use for small animal PET/CT imaging in a xenograft model.

Small animal Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging techniques are crucial in preclinical ...

Continuous Blood Sampling in Small Animal Positron Emission Tomography/Computed Tomography Enables the Measurement of the Arterial Input Function

For quantitative analysis and bio-kinetic modeling of positron emission tomography/computed tomography (PET/CT) data, the determination of the temporal blood time-activity concentration also known as arterial input function (AIF) is a key point, especially for the characterization of animal disease models and the introduction of newly developed radiotracers. The knowledge of radiotracer availability in the blood helps to interpret PET/CT-derived data of tissue activity. For this purpose, online blood sampling during the PET/CT imaging is advisable to measure the AIF. In contrast to manual blood sampling and image-derived approaches, continuous online blood sampling has several advantages. Besides the minimized blood loss, there is an improved resolution and a superior accuracy for the blood activity measurement. However, the major drawback of online blood sampling is the costly and time-consuming preparation to catheterize the femoral vessels of the animal. Here, we describe an easy and complete workflow for catheterization and continuous blood sampling during small animal PET/CT imaging and compared it to manual blood sampling and an image-derived approach. Using this highly-standardized workflow, the determination of the fluorodeoxyglucose ([18F]FDG) AIF is demonstrated. Further, this procedure can be applied to any radiotracer in combination with different animal models to create fundamental knowledge of tracer kinetic and model characteristics. This allows a more precise evaluation of the behavior of pharmaceuticals, both for diagnostic and therapeutic approaches in the preclinical research of oncological, neurodegenerative and myocardial diseases.

Here a protocol for continuous blood sampling during PET/CT imaging of rats to measure the arterial input function (AIF) is described. The catheterization, the calibration and setup of the system and the data analysis of the blood radioactivity are demonstrated. The generated data provide input parameters for subsequent bio-kinetic modeling.

For quantitative analysis and bio-kinetic modeling of positron emission tomography/computed tomography (PET/CT) data, the determination of the temporal ...

Medicine

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.

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

PET-CT Scanning for Multi-Tracer Study of Cerebral Oxygen and Glucose Metabolism

Multi-Tracer Studies of Brain Oxygen and Glucose Metabolism Using a Time-of-Flight Positron Emission Tomography-Computed Tomography Scanner

The authors have developed a paradigm using positron emission tomography (PET) with multiple radiopharmaceutical tracers that combines measurements of cerebral metabolic rate of glucose (CMRGlc), cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral blood volume (CBV), culminating in estimates of brain aerobic glycolysis (AG). These in vivo estimates of oxidative and non-oxidative glucose metabolism are pertinent to the study of the human brain in health and disease. The latest positron emission tomography-computed tomography (PET-CT) scanners provide time-of-flight (TOF) imaging and critical improvements in spatial resolution and reduction of artifacts. This has led to significantly improved imaging with lower radiotracer doses.
Optimized methods for the latest PET-CT scanners involve administering a sequence of inhaled 15O-labeled carbon monoxide (CO) and oxygen (O2), intravenous 15O-labeled water (H2O), and 18F-deoxyglucose (FDG)-all within 2-h or 3-h scan sessions that yield high-resolution, quantitative measurements of CMRGlc, CMRO2, CBF, CBV, and AG. This methods paper describes practical aspects of scanning designed for quantifying brain metabolism with tracer kinetic models and arterial blood samples and provides examples of imaging measurements of human brain metabolism.

Quantitative measurements of oxygen and glucose metabolism by PET are established technologies, but details of practical protocols are sparsely described in the literature. This paper presents a practical protocol successfully implemented on a state-of-the-art positron emission tomography-computed tomography scanner.

The authors have developed a paradigm using positron emission tomography (PET) with multiple radiopharmaceutical tracers that combines measurements of ...

Neuroscience

Neutron Radiography and Computed Tomography of Biological Systems at the Oak Ridge National Laboratory's High Flux Isotope Reactor

Neutrons have historically been used for a broad range of biological applications employing techniques such as small-angle neutron scattering, neutron spin echo, diffraction, and inelastic scattering. Unlike neutron scattering techniques that obtain information in reciprocal space, attenuation-based neutron imaging measures a signal in real space that is resolved on the order of tens of micrometers. The principle of neutron imaging follows the Beer-Lambert law and is based on the measurement of the bulk neutron attenuation through a sample. Greater attenuation is exhibited by some light elements (most notably, hydrogen), which are major components of biological samples. Contrast agents such as deuterium, gadolinium, or lithium compounds can be used to enhance contrast in a similar fashion as it is done in medical imaging, including techniques such as optical imaging, magnetic resonance imaging, X-ray, and positron emission tomography. For biological systems, neutron radiography and computed tomography have increasingly been used to investigate the complexity of the underground plant root network, its interaction with soils, and the dynamics of water flux in situ. Moreover, efforts to understand contrast details in animal samples, such as soft tissues and bones, have been explored. This manuscript focuses on the advances in neutron bioimaging such as sample preparation, instrumentation, data acquisition strategy, and data analysis using the High Flux Isotope Reactor CG-1D neutron imaging beamline. The aforementioned capabilities will be illustrated using a selection of examples in plant physiology&#160;(herbaceous plant/root/soil system)&#160;and biomedical applications&#160;(rat femur and mouse lung).

This manuscript describes a protocol for neutron radiography and computed tomography of biological samples using a High Flux Isotope Reactor (HFIR) CG-1D beamline to measure a metal implant in a rat femur, a mouse lung, and an herbaceous plant root/soil system.

Neutrons have historically been used for a broad range of biological applications employing techniques such as small-angle neutron scattering, neutron ...

Biology

Positron Emission Tomography

Positron emission tomography (PET) is a medical imaging technique involving radiopharmaceuticals &#8212; substances that emit short-lived radiation. Although the first PET scanner was introduced in 1961, it took 15 more years before radiopharmaceuticals were combined with the technique and revolutionized its potential.
One of the main requirements of a PET scan is a positron-emitting radioisotope, which is produced in a cyclotron and then attached to a substance used by the part of the body being investigated. This &#34;tagged&#34; compound, or radiotracer, is then put into the patient (injected via IV or breathed in as a gas), and how the tissue uses it reveals how that organ or other area of the body functions. For example, F-18 is produced by proton bombardment of 18O and incorporated into a glucose analog called fludeoxyglucose (FDG). How the body uses FDG provides critical diagnostic information. For example, since cancers use glucose differently than normal tissues, FDG can reveal cancers. The 18F emits positrons that interact with nearby electrons, producing a burst of gamma radiation. This energy is detected by the scanner and converted into a detailed, three-dimensional color image that shows how that part of the patient&#39;s body functions. Different levels of gamma radiation produce different amounts of brightness and colors in the image, which a radiologist can then interpret to reveal what is going on. For instance, a radioactive form of iodine can be used to monitor the thyroid and radioactive gallium can be used for cancer imaging.
The main advantage is that PET can illustrate the physiologic activity&#8212;including nutrient metabolism and blood flow&#8212;of the targeted organ or organs. In contrast, CT and MRI scans can only show static images. PET is widely used to diagnose a multitude of conditions, such as heart disease, the spread of cancer, certain forms of infection, brain abnormalities, bone disease, and thyroid disease. PET can also locate regions in the brain that become active when a person carries out specific activities, such as speaking, closing his or her eyes, etc. PET scans are now usually performed in conjunction with a computed tomography or magnetic resonance imaging scan for better data visualization and interpretation.
This content is derived from <a href="https://openstax.org/books/anatomy-and-physiology/pages/1-7-medical-imaging">Openstax, Anatomy and Physiology, Section 1.7: Medical Imaging</a> and <a href="https://openstax.org/books/chemistry-2e/pages/21-3-radioactive-decay">Openstax, Chemistry 2e, Section 21.3: Radioactive Decay</a> and <a href="https://openstax.org/books/physics/pages/22-5-medical-applications-of-radioactivity-diagnostic-imaging-and-radiation">Openstax, Physics, Section 22.5: Medical Applications of Radioactivity: Diagnostic Imaging and Radiation</a>

Positron emission tomography (PET) is a medical imaging technique involving radiopharmaceuticals &#8212; substances that emit short-lived radiation. ...