Nuclear molecular imaging

There are multiple methods of molecular imaging for clinical trials. The most common methods are optical fluorescence imaging and nuclear imaging. Read more about fluorescence imaging.

What is meant by nuclear imaging? Nuclear imaging uses radioactive pharmaceuticals and scanners to visualize processes in the body. A radioactive pharmaceutical can simply be a radioisotope that accumulates in the target of interest. For example, the use of a radioactive substance, radioactive isotopes of iodine, for the detection and treatment of thyroid cancer. Or a radioactive tracer for PET or SPECT that is coupled to a novel drug to add to the clinical trial imaging.

PET and SPECT are the two most used nuclear imaging techniques. They do differ in terms of resolution, sensitivity, quantification, availability, and costs. Because PET wins in terms of image quality and quantification, we mainly focus on that method. If availability and cost are important to you, we can discuss using SPECT instead of PET. To make the comparison yourself, we’ve written a comprehensive blog about SPECT vs PET. Because PET is often favorable, we use PET nuclear imaging examples on this page. However, feel free to ask us about SPECT clinical trials. In certain cases, a SPECT study can be the right solution.

Positron emission tomography (PET) is a medical imaging technique. As with other nuclear imaging modalities, PET uses low doses of radioactive substances to visualize biological processes in vivo. These radioactive substances can be referred to as tracers, or radiotracers. In a body, tracers will accumulate in areas with a higher degree of biochemical activity or higher receptor or transporter expression. Often a higher level of these processes coincides with the area of disease.

In early-stage drug discovery, research is done to identify these receptors. When the receptors or antigens have been identified, a compound that can bind to these antigens can be developed. At TRACER we are happy to share our knowledge on the many binding characteristics that we have experience with. Contact us to schedule a meeting.

In general, PET provides higher resolution nuclear images with a lower radiation dose than SPECT, but there are exceptions. The level of radiation is dependent on the dose administered to the patient, the energy of the gamma photons and the time the radionuclide is in the body. In this way, a SPECT bone scan can have a lower level of radiation than a PET bone scan. Fluorine-18 (F-18) labeled sodium fluoride (NaF) can be used for PET skeletal targeting. A Technetium-99m (Tc-99m) labeled bisphosphonates, such as methylene diphosphonate (MDP) used in SPECT, results generally in lower radiation exposure. Therefore, this SPECT method is currently still more commonly used than NaF PET.

Besides saving on costs and reducing the time to market, using PET in drug development has many other great advantages. The main advantage of PET is its very high sensitivity. This means very low concentrations of a radiopharmaceutical can be detected. As a result, low doses can be administered resulting in no or a very low biological effect of the radiopharmaceutical and low damage caused by the radiation. This way, biological processes in the body can be studied without saturating the molecular process. In a Phase 0 imaging clinical trial, only a microdose (subtherapeutic dose) is used. When using PET, a low dose can still result in very clear images.

Setting up a nuclear medicine test for an investigational new drug requires experience. There is a (radio) chemical aspect and clinical aspect of conducting such a clinical trial. When using radiopharmaceuticals in nuclear pharmacy and nuclear medicine a compound needs to be conjugated with a label. There is also the imaging part of nuclear molecular imaging. If done right, an imaging clinical trial provides valuable data on which your future drug development relies and benefits from. So why conduct a nuclear medicine study with TRACER?

• The founder of TRACER, prof. dr. G.M. van Dam is a pioneer in molecular imaging.
• Scientists at TRACER are highly experienced in nuclear imaging.
• TRACER is the only clinical research organization that provides nuclear imaging at this level.
• Because TRACER conducts clinical trials in the Netherlands, pharmaceutical companies benefit from fast regulatory approval times and hig accrual rates.
• The method that TRACER uses is approved by the FDA and EMA.

Still not sure if nuclear molecular imaging can benefit your drug development process? Contact us to gain insights from case studies.

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No, nuclear imaging differs from Magnetic Resonance Imaging (MRI) in its core mechanism.

Nuclear imaging uses a radioactive medicine that emits radiation from the body allowing a special camera to visualize the location and quantity of the compound. Nuclear imaging is part of nuclear radiology, while MRI falls under radiology but is not nuclear. No radioactive radiation is released during an MRI scan.

MRI uses specific radiofrequency waves to produce images. On MRI images anatomy can be studied and abnormalities can be discovered. Functional processes cannot be seen on MRI, while this is possible with SPECT or PET images. An example that makes this perfectly clear; it is possible to detect cancer at an earlier stage with PET/SPECT than with MRI or CT.
Source: https://jnm.snmjournals.org/content/48/1_suppl/28S and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075495/

Are molecular imaging and radiology the same? No, molecular imaging originated from radiology but differs from it. Molecular imaging combines molecular biology and in vivo imaging. Molecular imaging is a form of functional imaging since processes in the body are visualized. Molecular imaging / functional imaging has the goal to visualize processes in the body. Molecular imaging allows studying metabolism, blood flow, chemical processes, absorption, and more. Instead of just visualizing what can be seen by using X-ray or frequency waves, it uses biomarkers as targets. Using biomarkers and binding molecules to them to create images, sets molecular imaging apart from radiology.

What was the greatest benefit the medical and research industry gained when molecular imaging was discovered in the mid-twenties of the previous century? For medical purposes, molecular imaging allows detection and diagnosis of diseases at a very early phase. This is possible since it can detect changes in chemical processes that happen before visible anatomical abnormalities occur. For drug development and drug discovery the benefits are even greater.

Biodistribution and pharmacokinetics can be visualized in a clinical trial by using imaging. This is especially beneficial when molecular imaging is used in Phase 0. This first in human study allows drug developers to conduct a proof-of-concept (PoC) clinical trial at a very early stage in the drug development process. The PoC study is relatively inexpensive and can help with attracting the needed investment for the more expensive clinical trials that follow Phase 0.

For a Phase 0 imaging trial, a microdose of the investigational new drug labeled with a radionuclide is administered to the clinical trial participants. Molecular imaging visualizes on-target and off-target accumulation of the compound in the body. This allows researchers to determine whether the compound may be successful in subsequent clinical trials based on efficacy data. TRACER specializes in clinical research imaging with nuclear or fluorescent tracers.

A CT scan is very different from a nuclear scan based on how it is produced and what can be seen in the image. CT stands for Computed Tomography, and this definition is for ‘CT’ in SPECT the same. Sharing these letters does not mean that SPECT and CT are similar. CT and SPECT/PET are different based on the fact that the nuclear scan in SPECT/PET is constructed from radiation coming from within the body while a CT scan emits radiation externally through the body.

The difference between a conventional X-ray scanner and a CT scanner is that the X-ray tube in a CT scanner rotates during the scan. On the opposite angle of the transmitting X-ray source, a detector picks up the signal and transfers it to a computer. This makes the creation of 3D images from a CT-scan possible instead of 2D images (X-ray). The computer then constructs the images. On every rotation, an image of a slice between 1-10 mm is made.

The generated 3D image shows the skeleton, organs, and tissue. In general, the skeleton is very well visible while for some tissues a contrast agent is needed to form a clear image. Contrast agents are not radioactive. On the contrary, commonly used contrast agents like Iodine-based and barium-sulfate compounds block radioactive material and therefore allow the CT scan to make a better image.

Molecular imaging and nuclear medicine overlap but are not the same. Molecular imaging uses nuclear medicine to study the physiological processes in cells. In molecular imaging these nuclear medicines are called radiopharmaceuticals, coming from the words radioactive and pharmaceuticals. These radioactive pharmaceuticals are purely used in molecular imaging to form an image of what is happening at a molecular level. The smallest amount of radiation is used to minimize the risk to the patient.

On the other hand, nuclear medicines can also have a therapeutic effect. The nuclear effect is then intentionally used to damage cells by exposing them to radiation. You can see nuclear medicine examples in radiation therapy for cancer, like bone, liver, thyroid, and prostate cancer, neuroendocrine tumors, and non-Hodgkin lymphoma.

Molecular imaging can be done using nuclear medicine as in PET and SPECT. However, molecular imaging can also be done with other labels, tracers, or dyes. These can be fluorescent dyes or contrast agents for MRI and ultrasound. As long as a molecule is labeled for imaging, it can be seen as a method for molecular imaging. What method works for a specific application or study, depends on many factors.

Some things to keep in mind:

• A whole-body scan is often done with PET/SPECT.
• Uptake and distribution over time can be measured with a radioactive label.
• Fluorescence imaging has a very limited penetration depth depending on the tissue and is at the maximum around 3 centimeters.
• With MRI and CT imaging of anatomic structures is possible, but physiological processes cannot be seen.
• Function MRI (fMRI) and Molecular MRI (mMRI) are used in molecular imaging.
• Ultrasound can also be used in molecular imaging, it can provide data on types of tissue, blood flow, and motion.
• Molecular ultrasound involves imaging and even therapeutic uses of ultrasound by using contrast agents and biomarkers.

Nuclear scans allow us to visualize processes in the body. They are non-invasive, painless, and generally considered safe. Nuclear scans are used for diagnosis and therapy. For drug development nuclear scans visualize the biodistribution and pharmacokinetics of the investigational new drug (IND). When you participate in imaging clinical trials, the images are taken with PET or SPECT, and you are exposed to a small amount of radiation. Read the next question to learn more about this.

It is important to know that not every nuclear scan exposes the clinical trial participant or patient to the same amount of radiation. The amount of radiation can differ per type of radiopharmaceutical. It depends on the half-life of the radiotracer and the time between intake and excretion from the body. Here are several precautions after a nuclear scan or after the intake of a radiopharmaceutical.
– First of all, it is important to avoid contact with babies, children, and pregnant women for a period of several days.
– When participating in a clinical study where multiple scans are taken over a period of time, you can be asked not to drink too much since liquids help to flush the radiopharmaceutical out of the body.

Nuclear medicine exposes a participant in a clinical trial or a patient undergoing a PET or SPECT scan for diagnostic purposes to a very small amount of radiation. Nuclear medicines with a therapeutic effect expose the patient to a higher amount of radiation, as in the case of cancer radiation therapy. For a nuclear medicine scan, there can be side effects of nuclear medicine injection although they are not common. In general, the feeling of the radioactive injection for scan can be compared to that of a vaccination. When participating in a clinical trial, especially in a Phase 0 imaging clinical trial, the dosing is low/non-therapeutic.

In nuclear medicine and molecular imaging, the term nuclear refers to the use of radioactivity to create images from the radiation they emit. Nuclear can however have another meaning. Nucleus can refer in biology and chemistry to the central part of an atom. For instance, DNA is stored in the nucleus of a cell. In medicine, you find terms such as mononuclear infusion and mononuclear antibody. The first refers to the infusion of mononuclear cells. The second to monoclonal antibodies working together with mononuclear cells as in antibody-dependent cellular cytotoxicity ADCC.