Nuclear medicine techniques are frequently used medical imaging procedures for the diagnosis and staging of various diseases. Nuclear medicine imaging modalities detects radiation emitted from the administered radiopharmaceutical. There are several nuclear imaging techniques which are based on the different types of ionizing radiation: gamma emission and positron emission.
Gamma radiation, scintigraphy, and SPECT.
When a radioactive substance decays, it can emit various types of radiation: alpha, beta, gamma, or neutrons. For medical imaging, gamma rays can be detected by gamma cameras. Gamma photons are detected by crystals present in gamma cameras. In the crystals, the gamma photons are converted into photons of light. In turn, these photons are converted into an electric signal by a photomultiplier. Subsequently, electric signals are processed into an image.
As the gamma photons are emitted in all directions, gamma cameras are equipped with a collimator. A collimator is a Tungsten or lead device with channels that filters the gamma rays. Only the gamma rays perpendicular to the channels will go through and will be detected by the gamma camera (see figure 1). A gamma camera system usually consists of two detectors. By aiming the camera to the organ/region of interest, a two-dimensional image of this area is obtained. This method is called planar scintigraphy. Whole body imaging can be performed by acquiring several bed positions.
Single photon emission computed tomography (SPECT) uses the same principle as the gamma camera. With SPECT, 3-dimensional images can be obtained by acquiring several 2-dimensional images of the same area at different angles. For this, the gamma cameras rotate around the patient. The 2-dimensional images are then used to compute a 3-dimensional image.
Planar scintigraphy is one of the cornerstones of nuclear medicine and is still used in current clinical practice, although modern and more advanced imaging techniques are predominant nowadays. For example, planar scintigraphy with radiolabeled bisphosphonates is still used for the detection of bone metastasis of various types of cancer. Bisphosphonates accumulate in areas with high “bone turnover”, such as bone metastases.
Another example of is imaging of thyroid cancer and hyperthyroidism by radioactive iodine. Iodine is taken up by thyroid cells and in particular diseased thyroid cells. By using iodine-123, the diseases thyroid cells can be visualized. Consecutively, the diseased cells can be treated with the beta emitter iodine-131. As iodine-131 also has gamma emission, the treatment effect can also be visualized by imaging.
Positron emission and PET.
Another type of nuclear medicine imaging is based on the detection of isotopes that decay via positron emission. In this type of emission, a radioactive substance emits positrons. When a positron in its turn collides with an electron, annihilation takes place. During annihilation two photons are emitted in an angle of 180 degrees. With the imaging technique positron emission tomography, these emitted photons are detected and converted in an image. The photons are detected by a ring of detectors that surround the patient. When two photons are detected simultaneously by two detectors opposite each, it is likely to originate from an annihilation. The detection of these photo pairs will allow the determination of the location in the detector ring. All these events are the reconstructed into a 3-dimensional image.
The most often used radiopharmaceutical for PET is [18F]FDG (fluorodeoxyglucose). This radioactive analog of glucose is taken up by cells with a high metabolism. Since most tumor cells have an inefficient energy metabolism, they have a high glucose mechanism. As a result, tumor cells have a high accumulation of FDG.
Recently, a novel radiopharmaceutical is increasingly used for the detection of prostate cancer. The radiopharmaceutical targets the prostate specific membrane antigen (PSMA). PSMA is expressed at high density and incidence on prostate cancer cells. PSMA-ligands, labeled with gallium-68 or fluorine-18 are used to detect primary prostate tumors and their metastases. Moreover, PSMA-ligands labeled with alpha- or beta-emitters are used for prostate cancer radionuclide therapy. The therapy can be monitored by PSMA PET scans.
Differences between SPECT and PET.
Both PET and SPECT are powerful imaging tools to detect radiolabeled tracers. There are some differences between the imaging modalities. PET has a better spatial and temporal resolution. Moreover, PET is more sensitive than SPECT. Finally, quantification of radiotracer uptake is more accurate in PET compared to SPECT. In turn, SPECT is cheaper and easier to use, as the radiotracer production for SPECT is simpler in general. The production of most PET tracers requires a cyclotron and (complicated) synthesis protocols. For SPECT several commercially available labelling kits for radiopharmaceuticals are available. A radionuclide is added to these kits and the radiotracer is obtained. This requires less sophisticated facilities for production and quality control and can be performed in a general hotlab, available in most nuclear medicine departments.
PET and SPECT are highly sensitive imaging modalities that can detect very low concentrations of radiopharmaceuticals. Besides its use for diagnosis and staging of various diseases in clinical practice, PET and SPECT can be used for drug development. By labeling a new molecular entity (i.e., therapeutic compound) with a radionuclide, fast in human data can be obtained. Since PET and SPECT are highly sensitive, only very low amounts of the labeled drug have to be administered. Therefore, the first-in-human studies with a radiolabeled drug can be performed under the microdosing principle. With this FDA/EMA approved principle, only very low doses are administered, with no expected pharmacological effects or toxicity of the drug. As a result, only limited toxicity studies need to be executed. This reduces costs and speeds up the translational process significantly.
At TRACER we are specialized in first-in-human studies with the microdosing principle. We can assist you in the complete process of translation of your new drug for first-in-human studies.