**3. Detectors and imaging systems**

Diagnostic imaging refers to the techniques and processes used to create anatomical and functional images and is one of the fields in Medicine with the greater recent development [1].

The first reference to structural imaging dates to 1895, when Wilhelm Conrad Röntgen identified electromagnetic radiation in a wavelength range now known as X‐rays. Functional imaging started following the discovery of the scintillation scanner by Benedict Casen (using I‐131 as a radiotracer for diagnostic imaging purpose), and developed as a diagnostic specialty in 1958, when Hal Anger introduced the gamma camera (based on the principle of scintillation counting). Since then, Nuclear Medicine has considerably changed our view of looking at disease, by showing images of radiotracer distributions, providing functional images [1, 4].

The unique characteristics of Nuclear Medicine and Radiopharmaceuticals make dynamic, noninvasive studies and therefore are frequently used in the evaluation and development of new drug‐delivery systems. This chapter aims to review the different techniques available, their rationale and applications, using, whenever possible, examples from the literature as

Molecular imaging is defined as the visualization, characterization, and measurement of physiological mechanisms at the molecular and cellular levels, in living systems. Apart from Nuclear Medicine, it includes several other techniques, such as magnetic resonance imaging

One of the biggest advantages of molecular imaging is the ability to characterize specific dis‐ ease processes in different individuals, using noninvasive assessment and quantification; i.e., providing information that is inaccessible with any other imaging techniques or that other‐ wise would require more invasive procedures such as biopsy or surgery. Also, it identifies disease in its earliest phases and determines the precise location of a tumor, frequently be‐ fore symptoms occur or changes can be detected at the anatomical level. Identifying small differences between patients allows the tailoring of specific treatments for each individual

Nuclear Medicine is a molecular‐imaging modality that diagnoses and treats diseases using radioactive materials, known as radiopharmaceuticals. Radiopharmaceuticals, at diagnostic levels, have the ability to portray human physiology, biochemistry, or pathology without

For example, it can be used to identify the presence or absence of specific receptors or molecular changes, which are crucial for the selection of patients for certain targeted therapies [1].

This step for "personalized medicine" also allows a more precise identification of research

Diagnostic imaging refers to the techniques and processes used to create anatomical and functional images and is one of the fields in Medicine with the greater recent development [1].

The first reference to structural imaging dates to 1895, when Wilhelm Conrad Röntgen identified electromagnetic radiation in a wavelength range now known as X‐rays. Functional imaging started following the discovery of the scintillation scanner by Benedict Casen (using I‐131 as a radiotracer for diagnostic imaging purpose), and developed as a diagnostic specialty in 1958, when Hal Anger introduced the gamma camera (based on the principle of scintillation

well as from the authors' own experience.

160 Advanced Technology for Delivering Therapeutics

causing any physiological effect [1, 3].

**3. Detectors and imaging systems**

[1–3].

**2. Molecular imaging and Nuclear Medicine**

and spectroscopy, certain ultrasound technologies, and others [1, 2].

subjects, leading to more exact and cost‐effective clinical trials [3].

A gamma camera is single‐photon imaging equipment, also known as Anger camera or as scintillation camera. It contains a large radiation detector, consisting of a large thallium‐ activated sodium iodide crystal—the scintillator. A collimator, placed in front of the crystal, enables the γ‐rays to be focused onto the detector. Coupled to the crystal are photomultiplier tubes, which detect the light pulses. The whole detection part of the equipment is shielded from undesirable radiation. An electronic system links the photomultiplier tubes to a computer and visual display unit [1, 5, 6, 7].

The basic principle of gamma cameras is that radionuclide concentrations in the body can be measured *in vivo*, by detecting the photons emitted during their radioactive decay. The first gamma cameras were only able to create two‐dimensional (2D) representations. But in 1963, David Kuhl and Roy Edwards presented the first tomographic images using the Anger camera, by acquiring multiple planar images from different angles around the body and creating a three‐dimensional representation. This technology, called single‐photon emission computer‐ ized tomography (SPECT or SPET), is of special interest when studying complex three‐ dimensional anatomical structures [1, 6]. Besides static 2D and tomographic images, it is also possible to obtain dynamic, sequential images of the radiopharmaceutical's variation over time within a particular segment of the body [8].

Another indispensable nuclear‐imaging method consists of positron emission tomography (PET). The distinction between SPECT and PET is based on the physical properties of the radioisotopes used for imaging. SPECT (single‐photon imaging) relies on single γ‐ray photon emitters. By contrast, PET uses positron emitters—radioisotopes that simultaneously emit two 511‐keV photons, at approximately opposite directions. These photons are detected in the PET camera by a ring of detectors configured to detect coincidence. The registered events are then reconstructed into a three‐dimensional image [5, 9].

Although PET offers some advantages over SPECT, such as improved resolution and increased quantitative capabilities, SPECT is often more practical because of its wider availability and lesser cost [3].

A typical nuclear‐imaging procedure starts with the administration of the selected radiotracer, followed by image acquisition (through the detection of γ‐rays, X‐rays, or annihilation quanta in PET, using either a gamma camera or a PET scanner). The resulting image illustrates the tracer's location within the body [5, 10].

More recent developments in Nuclear Medicine include hybrid‐imaging techniques. Hybrid imaging refers to the fusion of two (or more) imaging modalities, such as SPECT/CT, PET/CT, or PET/magnetic resonance (MR) devices. These modalities have the advantage of condensing molecular and anatomical information in a single examination, thus surpassing one major drawback of highly specific tracers: the lack of anatomical landmarks within the image [3, 4].

It should be noted that Nuclear Medicine can also operate without imagery. This can be achieved by the measurement of radioactivity in specified sites of accumulation or in biological samples following the administration of the radiopharmaceutical [1, 8].
