Generally, semiconductor-based scatterer detectors are widely developed because of their high detection efficiencies and excellent energy resolutions. Table 1 lists the most commonly used semiconductors in detectors and their properties [56]. Among the different types of detectors used in Compton cameras, Si/cadmium telluride (CdTe) detectors are considered suitable for γ-ray measurements. The Si/CdTe Compton cameras exhibit a high energy resolution as well as a high angular resolution, especially for γ-rays of a few hundreds of keV. Si detectors are characterized by excellent energy and spatial resolutions because of the lower photoabsorption cross-sections of Si as well as the smaller Doppler broadening, compared with other semiconductors [57]. In contrast, CdTe detectors, which have a high density and a high effective atomic number, comprise high-resolution Schottky diodes, thus their energy resolution and efficiency are better than those of the Si detectors [58,59,60,61]. The beginning of the twenty-first century was marked by the development of Si/CdTe Compton cameras, as successors to COMPTEL, by Takahashi et al. [62,63,64]. These cameras use multiple layers of DSSDs, CdTe pixel detectors, and a highly advanced low-noise analog application-specific integrated circuit (ASIC) [63]. In DSSDs, highly doped p-type and n-type Si strips are implanted orthogonally to provide two-dimensional coordinate measurements. Meanwhile, the CdTe pixel detector is composed of indium as a common electrode side and the other platinum electrode side is pixelated, in which a thin layer of gold is evaporated for etching. Initially, a Si/CdTe Compton camera was developed as a soft γ-ray detector and launched into the low Earth orbit onboard the Hitomi satellite for the ASTRO-H mission, previously known as the NeXT mission, [67,68,69,70] in 2013 as a successor to the Suzaku X-ray mission [71,72,73,74]. The Si/CdTe Compton telescope can be operated at a moderate temperature of 0 to −20 °C. Following the Fukushima Daiichi Nuclear Power Plant disaster in 2011, because of the Great East Japan Earthquake [75], a Si/CdTe Compton camera, ASTROCAM, was built [76] to measure the radiation contamination (hot spots) at the accident site and in the surrounding environment, including the soil around plants and trees [77,78]. The camera consists of eight layers of Si detectors and four layers of CdTe detectors of (size: 5 cm × 5 cm and weights: 8–13 kg). These Si/CdTe cameras exhibit good energy and angular (2.2% at half maximum (FWHM) and 5°, respectively) resolutions for photons with an energy of 662 keV, and a high-count rate of 0.16 cps/MBq at a distance of 1 m. The medical applications of the Si/CdTe Compton camera were introduced by Sakai et al. [79], especially in nuclear imaging of different RIs, followed by improvements in the Compton imaging algorithms [80,81,82]. The in vivo [83] and human imaging [84] applications of Si/CdTe Compton cameras are vital achievements of these devices in the field of nuclear medical imaging.

A Si scatterer has a low sensitivity to high-energy (several MeV) γ-rays. Therefore, the feasibility of using these detectors to detect the γ-ray emissions of energies lower than those used in other beam-monitoring applications is currently under study. Parajuli et al. [85] used ASTROCAM for the monitoring of the range of C-ion beams used in radiotherapy by measuring the 511-keV annihilation γ-rays and 718-keV prompt γ-rays [86]. Shiba et al. [87] performed an in vivo monitoring of the annihilation γ-rays released from a mouse irradiated by a C-ion beam. Turecek et al. [88] reportedly developed a Si/CdTe Compton camera based on the Timepix3 technology. The study demonstrated the benefits of using Timepix3 technology that could enhance resolution and reduces Compton camera size. The Compton camera was revised with the application of only a single layer detector of CdTe [89] and the combination of the Timepix3 detector with the miniaturized MiniPIX TPX3 readout system. The performance evaluation of the camera demonstrated its feasibility to distinguish gamma sources located at near and further distances from the detector and could differentiate the source type by their energy. Tomita et al. [90] proposed and developed a vehicle-mounted 4π Compton imager based on the 3D pixel array CdTe detector. The position and activity of a single ¹³⁷Cs was estimated quantitively in 3D voxel space at three positions. Further, some other groups have assessed the feasibility of substituting CdTe with cadmium–zinc–telluride (CZT), which exhibits a comparatively higher resistivity and therefore lower leakage currents, to develop Compton cameras with suppressed background noise [91,92,93,94].

Ge detectors are popular alternatives to Si detectors in Compton cameras because of the advantageous characteristics of Ge over those of Si; for instance, HPGe has an excellent energy resolution of approximately 0.2% at 662 keV [95]. However, Ge-based detectors must be operated at very low cryogenically-regulated temperatures, owing to their small bandgaps [96,97]. Moreover, efficiency calibration is essential to perform measurements using HPGe detectors [98]. Ge detectors, such as Gammasphere [99], Euroballs [100], and AGATA [101], use Compton-suppressed arrays, and as a result, exhibit excellent energy resolutions, high efficiencies, and high peak-to-total ratios, thereby effectively mitigating the shortcomings of the NaI detectors [102]. Singh et al. [23,24] showed that the single Compton scatter efficiency of Ge is higher than that of Si, and thus the front-detector thickness should be minimal (<10 mm) to achieve an acceptable spatial resolution. They replaced the mechanical collimator with a 6 mm × 6 mm Ge detector as the front detector and measured the γ-rays emitted by ^99mTc (140 keV) and ¹³⁷Cs (662 keV) RI sources. Despite the resolution being poorer than expected, Ge-based front detectors are still preferred over Si detectors in Compton cameras for imaging photon energies in the wide range of 140–511 keV. An improved position-sensitive HPGe Compton camera, SmartPET (Smart Positron Emission Tomography), was developed and evaluated by Cooper et al. [103] and Boston et al. [104] at Liverpool University. The detector size was 60 × 60 × 20 mm³, the spatial resolutions were 7.7 and 6.3 mm for 511 and 1408 keV, and γ-ray emitting sources placed 50 mm away from the detector, respectively. To overcome this spatial resolution, Takeda et al. [105] developed a Ge-based hybrid Compton camera to image multiple probes. This detector showed a spatial resolution of 3.2 mm for an 834-keV γ-ray source placed 3.5 cm away from the camera. However, the efficiency decreased with the thickness of the mask, and the image reconstruction was more complex. Japan’s largest research institution, RIKEN, reportedly developed a Ge-based Compton camera, namely γ-ray emission imaging (GREI), for simultaneous and nondestructive imaging of radionuclides [106,107]. In this double-sided Ge detector, the active volumes of the scatterer and absorber are 39 × 39 × 10 and 39 × 39 × 20 mm³, respectively, and the strip pitch is 3 mm for both of the detectors. The detection efficiency of the GREI system for 662-keV γ-rays at a distance of 15 mm is approximately 0.01%. The GREI system was subsequently improved by narrowing the distance between the Ge detector elements (60–40 mm) and by increasing the data acquisition speed (GREI-II). The GREI and GREI-II systems were employed to evaluate and compare the distribution of bio-metals, such as ⁶⁴Cu and ⁶⁵Zn, using mouse models [38,108]. The research groups in RIKEN have renewed their efforts to implement GREI in clinical diagnostics for imaging multiple biological processes. Alnaaimi et al. [109] also developed a Ge-based Compton camera for medical applications and achieved an angular resolution of 9.4° ± 0.4° for a 662-keV γ-ray emitting source.

Scintillator-based Compton cameras possess a high detection efficiency, are less expensive, and are operable at room temperature, although their angular resolution is relatively lower than that of the semiconductor-based Compton cameras because of poor energy and position resolution. Popular scintillators usually used in Compton cameras are thallium-doped sodium iodide (NaI(TI)), thallium-doped cesium iodide (CsI(TI)), sodium-doped cesium iodide (CsI(Na)), cerium-doped gadolinium aluminum gallium garnet (Ce:GAGG), and cerium-doped lanthanum bromide (Ce:LaBr₃). The properties of scintillator detectors used in Compton cameras are listed in Table 2 [110,111]. Typically, scintillators are used with photomultiplier (PM) tubes or Si photodiodes. With the development of multipixel photon counters (MPPCs), which are a type of SiPMs, scintillators have become easier to use as scatterers in Compton cameras. Generally, the scintillation process occurs via three steps: the excitation of electrons, energy transfer of the excited or ionized electrons, and emission of fluorescence. Hofstadter et al. [112] discovered NaI(TI) in 1948 and it was the most widely used scintillator until the other scintillators were discovered. NaI(TI) and CsI(TI) possess a high sensitivity but an insufficient energy resolution in the low-energy range. Most radiopharmaceuticals used in nuclear imaging emit γ-rays with energies < 250 keV, such as ^99mTc (141 keV), ¹²³I (159 keV), and ¹¹¹In (171 and 245 keV), among which ^99mTc accounts for more than 50% of the RI-based medical diagnostics. Therefore, these scintillators are not suitable for Compton cameras used in medical applications, although they are still used in environmental radioactivity measurements [113,114,115]. In contrast, the properties of Ce:GAGG scintillators are superior to those of the other scintillators because they can emit Ce³⁺ photons with a 520 nm wavelength that originate from the 5d–4f transitions in Ce³⁺, possess high densities, and exhibit high light outputs, fast decay times, low self-radiation, and a good energy resolution [116,117]. Ce:GAGG exhibits a high stopping power and is neither hygroscopic nor self-emissive. The demands for Ce:GAGG-based Compton cameras rapidly increased after the Fukushima nuclear disaster in Japan in 2011 to measure the levels of different radioactive elements from a distance. Kataoka et al. [118,119,120] developed a portable and handheld Compton camera based on a Ce:GAGG scintillator and MPPC with a depth-of-interaction (DOI) capability. The camera contained 10 mm thick 50 × 50 mm² Ce:GAGG plates acting as both the scatterer and observer coupled with the MPPC, was initially used to detect radioactive elements [121]. The camera had an angular resolution of less than 10° for the source and 10 mm for the DOI configuration. Its angular resolution, measured at the FWHM, was approximately 8° at 662 keV. Since 2016, this group has been engaged in finding suitable methods to build a Compton camera for γ-ray imaging for particle therapy applications [122,123,124]. Kenichiro et al. [125] also developed a Compton camera, namely a Compton–PET hybrid camera, based on Ce:GAGG detectors and demonstrated simultaneous imaging with ¹³¹I and ¹⁸F RI sources. The Compton–PET hybrid camera consisted of two Ce:GAGG Compton cameras facing each other, with the target object at the central axis. Takahashi et al. [126] also reported on the development and performance of the stacked GAGG scintillator-based omnidirectional Compton imager for the objective of the rapid measurement of radioactive fallout, such as in nuclear accidents of the FDNP disaster. The three-dimensional position resolutions were estimated using the prototype Compton camera to evaluate the performance of several kinds of scintillators.

A typical Compton camera can only determine the scattering angle and cannot fully reconstruct the trajectory of the detected γ-rays. In electron-tracking Compton cameras (ETCCs), the tracking of the recoil electron reduces the Compton circle to a point and a significant background reduction can be achieved, compared with the conventional Compton cameras [127]. Tanaka et al. [128] developed the first ETCC that could detect Compton recoil electrons using a gaseous micro-time projection chamber (µ-TPC) detector and a position-sensitive scintillation camera enclosing the µ-TPC. The ETCC allowed three-dimensional (3D) position identification of the detected electron. Compared with other detectors, gaseous detectors show a better recoil–electron-tracking performance because of reduced multiple scatterings, although their detection efficiency is poor [130]. Muichi et al. [130] used various types of detectors as absorbers, one of which had a front detector sized at 10 × 10 × 8 cm³, a TPC (ethane) as the scatterer, and a 6 × 6 × 13 cm² gadolinium orthosilicate (GSO) scintillator array as the absorber [129]. The angular resolution of the ETCC was 6.6° at 360 keV for ¹³¹I. Subsequently, the angular resolution was improved to 4.2 ± 0.3° at 662 keV by replacing the GSO scintillator by a LaBr₃ scintillator [131]. Even though the efficiency and spatial resolution of the ETCC were lower than those of the other conventional Compton cameras, the high signal-to-noise ratio compensated for the low efficiency and resolution. They also reported simultaneous imaging of ¹³¹I and fludeoxyglucose (FDG) injected into mice [132]. After 2010, Tanimori et al. [133] and Mizumoto et al. [134] developed improved ETCCs and evaluated their astronomical and environmental γ-ray detection performances by changing the TPC size and gas parameters. However, these reported studies were more focused on the astronomical applications than on the nuclear medical imaging applications of ETCCs. To improve the detection efficiency, research is also being conducted to visualize the electron trails within solid-state detectors. The performance of Compton cameras would be greatly improved if the electron tracks in semiconductor or scintillator detectors could be visualized [135,136,137]. Jiaxing et al. [138] also reported the electron tracking algorithm using the Timepix3 based Compton camera, as Timepix3 possess an advantage of measuring the time and energy of an event simultaneously in each pixel. The demonstrative experiment result showed the significant enhancement of the angular resolution and the feasibility of the electron track algorithm. Yoshihara et al. [139] reported the development of a Compton imaging system that could track recoil electrons by using a combination of a trigger mode silicon-on-insulator (SOI) pixel detector and a gadolinium aluminum gallium garnet (GAGG) detector. The experimental results showed that the coincidence events were detected at a maximum rate of 1 cps for the measurement of 662 keV γ-rays of ¹³⁷Cs. They remarked that their Compton camera is suitable for imaging nuclides that emit 100–300 keV γ-rays.

In addition to the abovementioned Compton cameras, other Compton cameras based on semiconductor detectors and scintillators are under development. To counter the low sensitivities and high costs of Si-based Compton cameras, Katagiri et al. [140] developed a europium-doped calcium fluoride (CaF₂(Eu)) scintillator-based omnidirectional Compton camera for environmental radiation monitoring in nuclear medicine facilities. This CaF₂(Eu) scintillator-based Compton camera could detect γ-ray sources emitting energies < 250 keV. Four CaF₂(Eu) crystals, each with a diameter of 2.54 cm, were set as the vertices of a tetrahedral-structured scatterer and absorber. These Compton cameras could reportedly suppress ghost images and they exhibited a 12° angular resolution for ⁵⁷Co γ-rays, as well as better detection efficiencies.

Kasper et al. [141] developed a SiPM and a scintillation fiber-based Compton camera. Both the scatterer and absorber consisted of a thin elongated fiber made of a high-density inorganic scintillator (Ce:LYSO, Ce:LuAG, and Ce:GAGG) coupled with a SiPM. They tested the feasibility of using this Compton camera for beam monitoring in proton therapy and found that the camera with a Ce:LYSO scintillator exhibited a good proton beam monitoring performance.

Barrientos et al. [142] is currently working on the development and updating of LaBr₃-coupled SiPM-based Compton cameras (MACACO II) for proton beam monitoring. The MACACO II exhibits an energy resolution of 5.6% (FWHM) at 511 keV and an angular resolution of 8°.

Another popular Compton camera is the Polaris J^TM developed by H3D. Polf et al. [143] evaluated the detection (imaging) performance of this Compton camera, which is based on CZT detectors because of their high γ-ray interaction cross-sections for 6 MeV γ-rays. Polaris J consists of four stages, and each stage consists of a separate Polaris detection system containing a 20 × 20 × 15 mm³ CZT detector. The CZT detectors are pixelated in an 11 × 11 pattern on the x and y anode sides. The energy resolution of the Polaris J system is 9.7 keV (FWHM) at 662 keV (emitted by ¹³⁷Cs). This system is being further improved for proton therapy applications.

The Brookhaven National Laboratory, in collaboration with the National Aeronautics and Space Administration, is also developing a CZT-based Compton camera for astronomical observations [144]. The detecting plane is an array of 8 × 8 × 32 mm³ position-sensitive virtual Frisch-grid CZT detectors in the shape of bars and can detect the γ-ray interaction points better than any other CZT detector. Each module is a 4 × 4 detector subarray coupled with an ASIC. The detector exhibits a less than 1% energy resolution at 1 MeV and a submillimeter position resolution. The feasibility of this Compton camera is under study; it is expected to be sent to higher altitudes through balloon flights for sensitive measurements.