Marriage of radiotracers and total-body PET/CT rapid imaging system: current status and clinical advances

Abstract

Radiotracers and medical imaging equipment are the two main keys to molecular imaging. While radiotracers are of great interest to research and industry, medical imaging equipment technology is blossoming everywhere. Total-body PET/CT (TB-PET/CT) has emerged in response to this trend and is rapidly gaining traction in the fields of clinical oncology, cardiovascular medicine, inflammatory/infectious diseases, and pediatric diseases. In addition, the use of a growing number of radiopharmaceuticals in TB-PET/CT systems has shown promising results. Notably, the distinctive features of TB-PET/CT, such as its ultra-long axial field of view (194 cm), ultra-high sensitivity, and capability for low-dose tracer imaging, have enabled enhanced imaging quality while reducing the radiation dose. The envisioned whole-body dynamic imaging, delayed imaging, personalized disease management, and ultrafast acquisition for motion correction, among others, are achieved. This review highlights two key factors affecting molecular imaging, describing the rapid imaging effects of radiotracers allowed at low doses on TB-PET/CT and the improvements offered compared to conventional PET/CT.

Introduction

After the initial commercial introduction of positron emission tomography (PET) in 1978 [1], the imaging of human functional metabolism at the cellular-molecular level was realized, which has played a major role in noninvasive clinical imaging [2-4]. In the 21st century, PET combined with its contemporaneous computed tomography (CT) technology has an equally unparalleled role in detecting the metabolic functions of the human body [5]. It has a very high clinical sensitivity compared to other imaging techniques and has played a large role in clinical oncology, neurology, and cardiology while helping to develop new drugs [6,7].

With conventional PET scanners, the axial field of view (FOV) is 15 to 30 cm [3]. The limited axial field of view and the effect of imaging noise limit the study of dynamic imaging [2]. A long axial field of view (LAFOV) PET/CT scanner is clearly the best solution in terms of signal-to-noise ratio (SNR) sensitivity improvement and the time and economic cost of development (Figure 1) [2]. The first total-body PET/CT (TB-PET/CT) with a long-axis field of view of 194 cm was successfully created in 2015 with the investment of China United Imaging, the prototype of uExplorer is currently on the market [8]. In 2018, uExplorer completed its first small sample of scientific scans [8], which was approved by the FDA in the same year. Based on this, the Explorer team of scientists designed two updated products: Penn Explorer [9] and Mini Explorer [10]. In addition, the current LAFOV PET/CT imaging instruments include the Biography Vision Quadra system from Siemens [11].

Figure 1.

Schematic diagram of TB-PET/CT.

Its technical features include that TB-PET/CT has an extra-long axial field of view and ensures consistent sensitivity over an axial field of view of approximately 1 m at the center, and its 2.9 mm spatial resolution and fused time-of-flight technology achieve better imaging capabilities for small lesions, while the added time dimension allows for 4D panoramic imaging [12]. Its clinical advantages include a TB-PET/CT scanner with increased axial coverage, which improves the sensitivity of imaging, reduces the conventional PET imaging time from 10-20 mins to less than 40 s, reduces the radiation dose while improving the imaging quality, and achieves total-body dynamic imaging [13,14].

¹⁸F-FDG in TB-PET/CT

¹⁸F-FDG (Figure 2A), the most commonly used radiographic agent in clinical practice, is a glucose analog that accurately reflects glucose metabolism levels in organs/tissues in the body [15]. The relatively hypoxic environment of cancerous tissues requires ten times more glucose for cellular metabolism than normal cells [16]. Therefore, ¹⁸F-FDG will be heavily concentrated in the malignant tumor area and make the radioactive intensity in the tumor area significantly different from that in normal tissue.

Figure 2.

Structure and application of ¹⁸F-FDG, a nonspecific tracer. Structural formula of ¹⁸F-FDG (A). First clinical application of TB-PET/CT, the imaging quality of a patient over 7 scans (B). PET images of a 63-year-old patient with esophageal cancer at 1 min, 2 mins, 4 mins, 8 mins, 10 mins, and 15 mins (left), where the imaging quality at 2 mins is equivalent to that at 8 mins (right) (C). Staphylococcus aureus infection was detected by TB-PET/CT imaging at the dorsum of the right foot and the entrance to the inferior vena cava (D). Biograph Vision Quadra System 120 s acquisition of CT, PET, PET/CT, and maximum-intensity-projection reconstruction (from left to right) ¹⁸F-FDG was not pathologically uptaken, and the arrow in the figure indicates partially reactive aggregation (E). Images reprinted from [8,26,29,32] with permission.

Although FDG-PET/CT has the potential for noninvasive, precise medical imaging, it still suffers from false-negative detection and inefficient detection of photons emitted by the radiotracer [17-20]. The difficulty of detecting osteogenic metastases due to low levels of glucose metabolism in osteogenic metastases was identified as early as 1998 [17]. Examples include Cook’s report of 23 false-negative PET-CT cases of bone metastases in patients with breast cancer [17] and An’s report of a false-negative PET-CT case of bone metastases in a patient with non-small cell lung cancer [19].

LAFOV PET can improve the sensitivity of PET scans by covering the entire body. Compared to conventional PET scanners, LAFOV PET can be 10 to 40 times more sensitive, thus enabling the detection of small, low-density tumor deposits (micrometastases) [8,12,21,22]. The first application of TB-PET/CT was quantitatively evaluated in four subjects using decreasing doses of the tracer ¹⁸F-FDG (4.5 MBq/kg, 4.5 MBq/kg, 1.35 MBq/kg, 0.45 MBq/kg) for possible imaging improvements with TB-PET/CT. Subject 1 illustrated the feasibility of faster and better imaging, with images of diagnostic quality in 37.5 seconds, good detectability of small lesions in 20 minutes, and low image noise (Figure 2B). Subject 2 illustrated the feasibility of later imaging, with imaging images still of diagnostic quality 10 hours after injection, and their repeat scans demonstrated the feasibility of high temporal resolution whole-body dynamic image production. Subject 3 illustrates that single-organ distal imaging with low-dose injection still has a good SNR. The hypothesis of TB-PET/CT was initially verified by the tracer ¹⁸F-FDG. The clinical advantages of TB-PET/CT include improved image quality, rapid scanning, multiple post half-life delayed scanning, low-dose scanning, and whole-body pharmacokinetic imaging [8].

Applications in cancer

Modern medical advances have prolonged the life span of patients with chronic malignancies, and the emergence of dynamic imaging with TB-PET/CT scans will also help in personalized and precise treatment as well as side effect management. TB-PET/CT often allows for half-dose whole-body imaging, reducing the radiation dose while improving imaging quality. Tan et al. compared half-dose ¹⁸F-FDG (1.85 MBq/kg) TB-PET/CT and clinical routine full-dose ¹⁸F-FDG PET/CT lung cancer image quality in a group including 56 patients with primary lung cancer, and the image quality score was significantly higher in the half-dose group (4.3±0.7) than in the full-dose group (3.7±0.6) (P=0.004) [23]. Based on previous studies, Sachpekidis et al. determined the appropriate acquisition time range for LAFOV Biograph Vision Quadra PET/CT by a low dose (2 MBq/kg) in 49 patients with melanoma, ultimately reducing the conventional acquisition time (10 mins) to 5 mins without affecting the liver SNR and tumor-background ratio (TBR) [24].

In PET/CT, diagnostic imaging quality is not only related to tracer dose, but image quality and noise level are also negatively correlated with acquisition time. Hu et al. performed a diagnostic evaluation of ¹⁸F-FDG TB-PET/CT (uExplorer) with fast 2-min acquisition versus conventional ¹⁸F-FDG-PET/CT (uMI780) in 156 patients with hepatocellular carcinoma divided equally into two groups. The imaging quality of TB-PET/CT in the naked eye was the same at 2 mins and 15 mins. In addition, the cancer detection efficiency of TB-PET/CT imaging with 2 mins rapid acquisition was similar to that of conventional PET/CT [25]. They also performed total-body imaging with low-dose ¹⁸F-FDG (0.37 MBq/kg) in 30 tumor patients. Based on the above experience with rapid imaging, a full-dose 2 minutes imaging control group was established in this experiment. Low-dose 8 mins imaging results were of comparable quality to the control group and had acceptable medical diagnostic value (Figure 2C) [26]. Zhang et al. explored the image value of a more rapid TB-PET/CT scan, comparing 300-second data with 30-second data from TB-PET/CT after injection at a conventional dose (3.7 MBq/kg). Through the analysis of 110 lesions in 84 patients, although the 300-second data had higher sensitivity and accuracy than the 30-second data, the TB-PET/CT images obtained by the 30-second acquisition time reached the diagnostic level of traditional PET/CT. For patients with malignant tumors that cannot be located for a long time, 30-second rapid whole-body PET/CT meets the clinical diagnostic requirements [27].

Applications in infectious diseases

After entering the body, the radiotracer ¹⁸F-FDG is taken up preferentially by macrophages and inflammatory cells in tissues. Therefore, ¹⁸F-FDG has become the pillar of molecular imaging for infectious diseases (fungal, bacterial, and viral infections) [28]. Traditional ¹⁸F-FDG-PET imaging strategies are limited in the therapeutic diagnosis of infectious diseases in the context of complications. TB-PET/CT imaging has emerged in recent years with high sensitivity and the ability to detect low-level signals from background noise. Therefore, new ¹⁸F-FDG TB-PET/CT strategies will be at the forefront of clinical and pathogenesis research in infectious diseases [28].

Rijsewijk et al. performed TB-PET/CT imaging using an ultra-low dose of ¹⁸F-FDG in a 10-week-old neonate with S. aureus sepsis, and the scan identified 2 foci of infection, one on the dorsum of the right foot near the venous access and the other on the base of the right atrium at the entrance to the inferior vena cava, and post-sampling confirmed the foot lesion as Staphylococcus aureus infection (Figure 2D) [29]. This case also confirmed the ability of low-dose ¹⁸F-FDG TB-PET/CT to image infectious diseases. Chronic (and acute) viral infections such as HIV have been experienced with PET imaging for decades. Since the beginning of the COVID-19 pandemic, the study of infectious diseases in PET imaging has received further attention. Conventional PET/CT is limited by its sensitivity and low SNR, making the study of the pathogenesis of infectious diseases missing as well as false-negative scans in patients with clinical mild infections and small lesions [3].

Applications in pediatric imaging

The first consideration in pediatric PET imaging is the dose of radiopharmaceuticals to be used, as children have higher tissue radiosensitivity and longer life expectancy than adults [30,31]. LAFOV PET/CT’s fast scans and low-dose imaging can help reduce the radiation dose in children [32].

Chen et al. summarized 100 pediatric tumor patients receiving half a dose of ¹⁸F-FDG (1.85 MBq/kg) using uExplorer imaging to reconstruct PET images at a complete 600-second time. The imaging quality of 300 s, 180 s, 60 s, 40 s, and 20 s was compared, and sufficient image quality and clear lesions could be obtained at a fast scan time of 60 seconds and half-dose activity [31]. A study by Zhao et al. found that optimal image quality was achieved with TB-PET/CT by reducing the dose given to 1/10th of the dose (0.37 MBq/kg) [33]. Reichkendler et al. imaged a 17-month-old girl with suspected malignancy or focal infection after left heminephrectomy with TB-PET/CT using the Biograph Vision Quadra system. The results of diagnostic value were obtained without the use of sedation, and malignancy or focal infection was ruled out based on the imaging results (Figure 2E) [32]. Li et al. performed uExplorer PET/CT total-body dynamic scanning using a half-dose tracer ¹⁸F-FDG (0.05 mCi/kg) in a sedation-free child to reduce the acquisition time without affecting the image quality even in the presence of involuntary movements of the child [34]. The above examples demonstrate the advantages of longaxis PET/CT in pediatric imaging, allowing for low-dose, high-quality imaging while reducing motion artifacts and avoiding anesthesia.

Specific tracers in TB-PET/CT

Application in prostate cancer-PSMA

Prostate cancer (PC) is the third most common cause of cancer-related death among men worldwide [35,36]. Given the limitations of other PET radiopharmaceuticals, there is increasing research on radiotracers based on targeting prostate-specific membrane antigen (PSMA) [35]. At present, the most commonly used tracers for PET imaging are ⁶⁸Ga-PSMA-11 (1, Figure 3) [37-40], and ¹⁸F-PSMA-1007 (2, Figure 3) [41-44]. However, these are all studies based on conventional imaging, in contrast to TB PET/CT, which has advantages such as high sensitivity, large dynamic range, and high image quality. Therefore, Alberts et al. injected ¹⁸F-FDG, ¹⁸F-PSMA-1007, or ⁶⁸Ga-DOTATOC and performed double scans in 44 patients [45]. The performance of the LAFOV Biograph Vision Quadra PET/CT and the standard axial field of view (SAFOV) Biograph Vision 600 PET/CT system was studied. The results showed that LAFOV captured the same range of integrated activity as SAFOV. In clinical conditions, the LAFOV system has higher sensitivity, with improvements in image quality, lesion quantification, and SNR. Compared to conventional SAFOV acquisition (equivalent to 16 mins of FOV coverage), the LAFOV system can provide images of comparable quality and quantification of lesions within 2 mins.

Figure 3.

Chemical structure of tracers.

Imaging 1 h after injection of ⁶⁸Ga-PSMA-11 is the conventional imaging acquisition time, but this is not the optimal imaging time choice [46,47]. Although the acquisition of images after a longer acquisition time can improve lesion uptake and contrast, there are many limitations, such as the decay of the short half-life (68 mins) during later imaging and the reduced availability of the scanner due to the longer acquisition time [48]. With the advent of a large dynamic range and highly sensitive LAFOV scanners, late imaging of radiopharmaceuticals can be effectively tracked [2]. Alberts et al. studied standard imaging at 1 h and late imaging at 4 h in 10 patients after injection of ⁶⁸Ga-PSMA-11 [49]. The results showed that the average tumor to the background of 4 h was higher and the SNR was improved compared with 1 h. This suggested that a later acquisition time may be better when using LAFOV for ⁶⁸Ga-PSMA-11 imaging.

In addition to effectively tracking late imaging, TB imaging PET/CT can also determine the optimal time for prostate cancer ⁶⁸Ga-PSMA PET/CT imaging. Wen et al. studied the time-activity curves of pathological lesions of tumors and physiological bladder activity using TB-PET in 11 patients and determined the optimal imaging time [50]. The study showed that early assessment of pathological lesions with dynamic ⁶⁸Ga-PSMA PET could avoid interference with bladder activity. However, compared to imaging at 60 mins, early imaging may miss lesions with low PSMA uptake. Looking at the above factors, combining the first 6 minutes of early dynamic imaging with later static imaging can better detect lesions masked by bladder activity and lesions with relatively low PSMA uptake. In addition, they found that ⁶⁸Ga-PSMA PET imaging can also be performed 35-59 minutes after injection to reduce the wait time for imaging. They also studied the mean SUV values of the lesion and metastasis at 180 mins of delayed imaging and found that they were higher than those at 35 mins and 60 mins, indicating that delayed imaging can also satisfy the needs of clinical diagnosis.

The addition of additional 2-¹⁸F-FDG PET/CT with higher sensitivity compared to the single PSMA tracer PET/CT can help detect lesions with low expression [51]. Based on this, Alberts et al. used the LOFOV PET/CT system to perform ⁶⁸Ga-PSMA-11 and an additional low-dose 2-¹⁸F-FDG PET/CT scan on 14 patients who were to undergo PSMA radioligand therapy examination [52]. The results of the study showed that one in 14 patients (7%) had other lesions with low or absent PSMA expression but high FDG affinity. This demonstrated that additional low doses of 2-¹⁸F-FDG-PET/CT can be used as part of the efficacy evaluation of ¹⁷⁷Lu-PSMA radioligand therapy, helping to reveal lesions with low PSMA affinity (Figure 4) [52].

Figure 4.

(A, C) show ⁶⁸Ga-PSMA-11 PET/CT and (B, D) show additional PET/CT performed 1 h after additional FDG administration. Images reprinted from [52] with permission.

Specifically, targeted tracers allow for high uptake at the target site and rapid clearance at the injection site. The application of specifically targeted tracers to TB-PET/CT enables the staging of cancer patients and supports personalized patient treatment. For prostate cancer, it is mentioned here that two specific radiotracers with safety and efficacy, ¹⁸F-DCFPyL (3, Figure 3) and ⁶⁴Cu-SARbisPSMA (4, Figure 3), can be used for TB-PET/CT imaging. ¹⁸F-DCFPyL is a radiolabeled, highly selective small molecule PET tracer targeting the membrane protein PSMA, which has good pharmacokinetic properties and is capable of detecting a large number of metastatic suspicious lesions in prostate cancer [53]. ⁶⁴Cu-SARbisPSMA has now completed a phase I clinical study (NCT04839367) to demonstrate its tolerability and safety [54].

TB-PET/CT enables early visualization of tracer kinetics, based on which more valuable radiotracers can be screened. Ingbritsen et al. sequentially injected ¹⁸F-DCFPyL (1.2 MBq/kg) and ⁶⁴Cu-SARbisPSMA (1.66 MBq/kg) in a 69-year-old male patient with prostate cancer restaging to detect angiomyolipoma, followed by dynamic imaging and delayed imaging by the Biograph Vision Quadra system, and ¹⁸F-FDGTB-PET/CT scans were performed a few days later [55]. Both ¹⁸F-DCFPyL and ⁶⁴Cu-SARbisPSMA showed good lesion uptake compared to ¹⁸F-FDG. Imaging comparisons at 1 h after injection showed higher ⁶⁴Cu-SARbisPSMA blood pool activity than ¹⁸F-DCFPyL, and ⁶⁴Cu-SARbisPSMA remained more radioactively retained at 6 h and 30 h in ribs and angiolipomas [55].

Application in neuroendocrine tumor-⁶⁸Ga-DOTATATE

Neuroendocrine tumors are a heterogeneous group of tumors whose main hallmark is the expression of somatostatin receptor 2 (SSTR2) [56]. PET imaging of ⁶⁸Ga-DOTATATE (5, Figure 3) showed a particularly high binding affinity (0.2±0.04 nM) to SSTR2-positive tissues [57]. In terms of dosing, the recommended dosing activity for ⁶⁸Ga-DOTA-conjugated peptides was between 100 and 200 MBq, and at least 100 MBq was required to obtain good image quality. In addition, the sensitivity of the PET detector and the patient’s weight also affect the injection activity [58]. The TB PET detector with ultra-high sensitivity can achieve good image quality with low doses of tracers. Based on this, Shi’s group found that low injected ¹⁸F-FDG activity was sufficient to obtain good image quality and did not reduce the detection efficiency of lung cancer [23]. In addition, TB PET detectors can significantly shorten the tracer acquisition time of conventional doses within 2 mins to obtain adequate ¹⁸F-FDG PET/CT image quality [59].

Based on the results, their group investigated the feasibility of receiving a low injection dose of ⁶⁸Ga-DOTATATE TB PET/CT examination in 57 neuroendocrine tumor patients [60]. The results showed that good subjective image quality can be obtained within a 3 mins acquisition time. This suggested that a low dose of ⁶⁸Ga-DOTATATE TB PET/CT not only reduces acquisition time but also maintains adequate image quality for patients with neuroendocrine tumors.

Application in urothelial carcinoma-⁶⁸Ga-N188

Nectin cell adhesion molecule 4 (nectin-4) is limited in expression in most normal tissues [61,62]. In urothelial carcinoma, it is present in more than 80% of tumor samples and is an emerging biomarker for the diagnosis and treatment of tumors [61]. Duan et al. designed a bicyclic peptide radiotracer, ⁶⁸Ga-N188, targeting nectin-4 and used uExplorer TB-PET/CT for the first clinical evaluation on patients with advanced uroepithelial cancer [63]. Based on the dynamic imaging results from 3 patients with different nectin-4 expression levels, they found that the uptake of nectin-4-positive lesions was obvious at 600 s and 2400 s, while the uptake of nectin-4-negative lesions was less obvious. In addition, from the time distribution results of full dynamic imaging, nectin-4-positive lesions reached the maximum uptake value in approximately 14 mins. The results showed that ⁶⁸Ga-N188 had a high affinity for nectin-4, and TB PET/CT allowed for faster maximum imaging.

Application in pancreatic and gastric cancer-⁶⁸Ga-FAPI-04

Fibroblast activation protein (FAP) is an ideal diagnostic and therapeutic target for malignant tumors [64-66]. ⁶⁸Ga-FAPI-04 (6, Figure 3) is a radioactive tracer that targets FAP and can specifically identify tumor cells [67-69]. Long-axis PET/CT enables dynamic whole-body imaging compared to short-axis PET/CT used in previous clinical studies. Shorten the imaging time could achieve multi-parameter imaging from ⁶⁸Ga-FAPI-04 PET. Therefore, Chen et al. studied the feasibility and superiority of ⁶⁸Ga-FAPI-04 PET imaging versus conventional SUV imaging in 13 patients [70]. They performed image analysis of the kinetic parameters of the two-tissue reversible compartment model (2T4K) and the multigraph models. The results showed that the TB imaging results of ⁶⁸Ga-FAPI-04 PET were better in the SUV, and the lesion contrast was enhanced. Both V_T (2T4K) images and V_T (Logan with spatial constraint (SC)) images showed lower image noise and higher lesion significance than SUV images. Compared with conventional short axis PET/CT, PET/CT can be used for dynamic total-body imaging of TB. Rhythm spatial synchronization makes it feasible for parametric imaging.

Application in Parkinson’s disease-¹¹C-CFT

¹¹C-2-beta-carbomethoxy-3-beta-(4-fluorophenyl) tropane (¹¹C-CFT) (7, Figure 3) is a radiolabeled cocaine derivative that binds specifically to dopamine transporters located at the synapses of the anterior membrane in the brain [71]. It is used in the diagnosis of Parkinson’s disease. Commonly used ¹⁸F-FDG for PET/CT imaging of cerebral glucose metabolism does not specifically distinguish atypical Parkinson’s syndrome in brain diagnosis. ¹¹C-CFT with specific binding to brain dopamine transporter PET imaging is symmetrically distributed in the striatum bilaterally in normal subjects and is differentially reduced in patients with Parkinson’s disease [71]. However, the short half-life of ¹¹C (20.4 mins) and the incomplete understanding of its human biodistribution limit its clinical application.

TB-PET/CT, which allows whole-body dynamic scanning and enables fast imaging, will help ¹¹C-CFT for the diagnosis of Parkinson’s disease and increase the understanding of the human biodistribution of radiotracers. Xin et al. injected 373.3±71.56 MBq of ¹¹C-CFT tracer in six male patients suspected of Parkinson’s disease, followed by dynamic TB-PET/CT using uExplorer, and a 75-minute PET scan described the biodistribution in PD patients in real time (Figure 5) [72]. Tracer uptake and metabolism are rapid in the kidneys, lungs, spleen, and thyroid, with rapid uptake and slow metabolism in the heart wall, slow uptake and metabolism in the liver, and generally low uptake in the brain and muscle, resulting in “low-level extension”. Meanwhile, the effective dose of ¹¹C-CFT TB-PET/CT is 2.83E-03 mSv/MBq, a two-thirds reduction in dose compared to conventional multi-bed PET/CT scanning technology [72]. This example demonstrates the value of ¹¹C-CFT in TB-PET/CT imaging of Parkinson’s disease by demonstrating good whole-body biodistribution, a very low injection dose, and high imaging quality.

Figure 5.

TB-PET/CT imaging results of a Parkinson’s patient showing ¹¹C-CFT at five time points of body circulation (top) as well as four nodes of brain uptake (bottom). Images reprinted from [72] with permission.

Application in cancer immunotherapy monitoring-⁸⁹Zr-trastuzumab

⁸⁹Zr-labeled antibodies represent promising reagents for cancer immunotherapy monitoring. Several of these radiopharmaceuticals have already been utilized in clinical settings, such as ⁸⁹Zr-atuzumab, ⁸⁹Zr-anti-CD8 microantibodies, and ⁸⁹Zr-trastuzumab [73-76]. However, most currently available commercial scanners lack a sufficient SNR for image reconstruction and accurate interpretation and quantification within the 2-3 physical half-life (25 s) range [22]. Consequently, extending PET imaging beyond 7-10 days post-injection with acceptable radiation exposure remains challenging, even for ⁸⁹Zr, a positron emission isotope with a long half-life [77].

Berg et al. demonstrated the feasibility of extending the ⁸⁹Zr-PET study up to 30 days post-injection using the high-sensitivity primate Mini Explorer PET system. In a study involving 12 young rhesus macaques, the pharmacokinetics of four Zr chelator linkers associated with humanized IgG antibodies were evaluated. Through quantitative image analysis of differential bone and liver uptake at later time points using total-body PET/CT, enhanced stability of the ⁸⁹Zr chelator was achieved using the octacectaate chelator DFO*. Even at very late time points, remarkable agreement was observed within each group, enabling the observation of variations in tissue and bone uptake of different chelators and linkers [78].

Conclusions

The utilization of long-axis PET/CT in clinical practice has demonstrated its ability to achieve high-quality imaging with a low-dose radiotracer, due to its ultra-high sensitivity and SNR. This advancement has paved the way for various clinical applications including whole-body dynamic imaging, delayed imaging, personalized disease management, and ultrafast acquisition for precise motion correction. The development of the TB-PET/CT system has further expanded its capabilities by enabling delayed imaging and multiple repeat imaging. Because of the delayed imaging capability of TB-PET/CT, allows for the meaningful utilization of longer half-life radionuclides and introduces new possibilities with long-lived radionuclides. Although the availability of TB-PET/CT imaging systems is currently limited to a few institutions, the existing imaging results have already demonstrated the superiority of TB-PET/CT over conventional imaging methods. As long-axis imaging systems continue to gain wider usage and a broader range of radiopharmaceuticals are incorporated, LAFOV PET/CT has the potential to not only aid in disease identification but also greatly contribute to drug development, disease follow-up, screening of high-risk populations, and other yet unimagined applications.

Disclosure of conflict of interest

None.