# Immuno-PET for Glioma Imaging: An Update
## 3 Immuno-PET: Basic Principles and Technical Features  
The use of radiolabeled antibodies for cancer imaging is not something new. In past years, immuno-scintigraphy, based on the administration of antibodies labeled with gamma-emitting radionuclides (i.e., 99 mTc and 123I), has been applied with encouraging results in several clinical settings [23]. As concerns gliomas, monoclonal antibodies (mAbs), specifically those recognizing the type III mutant EGFR (EGFRVIII), were found to specifically accumulate into subcutaneous or intracranial glioma xenografts expressing the EGFRVIII [24]. Nevertheless, the use of immunoscintigraphy has been limited by the low resolution of planar imaging obtained with a gamma-camera, which is only partially overcome by the implementation of hybrid SPECT/CT [25; 26]. Immuno-PET is a cutting-edge medical imaging technique that has revolutionized the field of molecular imaging and cancer diagnostics [27; 28]. This powerful technology combines the specificity of antibodies with the high-resolution imaging capabilities of PET scans to provide valuable insights into the molecular and cellular processes occurring within the body. Immuno-PET holds immense promise in cancer diagnosis, treatment monitoring, and drug development, as it allows for the visualization and quantification of specific biomarkers and immune responses. The fundamental principle of immuno-PET lies in its ability to target and visualize specific molecules or cells within the body. At its core, immuno-PET involves the use of radiolabeled antibodies, or antibody fragments, which are designed to bind with high affinity to particular biomarkers or antigens present on the surface of cancer cells, immune cells, or other disease-related targets. These radiolabeled antibodies are usually coupled with a positron-emitting radionuclide, such as fluorine-18 (\({}^{18}\)F) or copper-64 (\({}^{64}\)Cu), which emits positrons. When injected into the patient's bloodstream, these radiolabeled antibodies circulate throughout the body, seeking out and binding specifically to their target antigens. However, in the advancement of immuno-PET, a pivotal milestone has been the creation of antibodies tagged with zirconium-89 (\({}^{89}\)Zr), a positron-emitting element with a physical half-life of 78.4 h [29]. This half-life aligns with the extended presence of antibodies within the body following administration, facilitating their use. A schematic representation of immuno-PET in gliomas is depicted in Figure 1.  
Once the radiolabeled antibodies have localized at the target site, the emitted positrons undergo annihilation reactions with nearby electrons, resulting in the release of gamma rays in opposite directions. These gamma rays are then detected by a PET scanner, which is equipped with sensitive detectors arranged in a ring around the patient's body. By measuring the spatial distribution of these gamma rays, the PET scanner creates a three-dimensional image of the concentration and distribution of the radiolabeled antibodies within the body [30]. This provides a detailed map of the location and extent of the targeted molecules or cells. Because radiolabeled antibodies are highly selective for their target antigens, immuno-PET can detect even low levels of specific biomarkers with great precision. This is particularly valuable in the context of cancer diagnosis, where the early detection of tumor-associated antigens can lead to earlier and more effective treatments. Additionally, Immuno-PET can differentiate between cancerous and non-cancerous tissues, reducing false positives and improving diagnostic accuracy. Another important aspect of immuno-PET is its ability to provide quantitative information. Unlike traditional imaging techniques like CT or MRI, immuno-PET allows for the measurement of biomarker expression levels and changes over time [31].