Fibroblast Activation Protein Inhibitor PET/CT in Gastric Cancer.

Like other major cancers, gastric cancer expresses fibroblast activation protein (FAP) in cancer-associated fibroblasts. Many recent studies have reported the utility and superiority of FAP inhibitor (FAPI)-PET over [18F]fluorodeoxyglucose (FDG)-PET in gastric cancers, from initial staging to recurrence detection. FAPI-PET shows higher accumulation in primary sites and metastatic lesions than does FDG-PET, especially for the detection of peritoneal carcinomatosis. In the case of gastric signet ring cell carcinoma, FAPI-PET showed excellent performance, as uptake is usually weak on FDG-PET in this cohort.

FAPI PET/CT research progress in digestive system tumours.

18F-fluorodeoxyglucose positron emission tomography/computed tomography has been used in clinical practice for many years. This modality is of great value for tumour diagnosis, staging, and efficacy evaluations, but it has many limitations in the diagnosis and treatment of digestive system tumours. Fibroblast activation protein is highly expressed in gastrointestinal tumours. Various isotope-labelled fibroblast activation protein inhibitors are widely used in clinical research. These inhibitors have low background uptake in the brain, liver and oral/pharyngeal mucosa and show good contrast between the tumour and background, which makes up for the lack of fluorodeoxyglucose in the diagnosis of digestive system tumours. It better displays the primary tumours, metastases and regional lymph nodes of digestive system tumours, such as oesophageal cancer, gastric cancer and liver cancer, and also provides a new method for treating these tumours. Based on this background, this article introduces the current research status of fibroblast activation protein inhibitor positron emission tomography/computed tomography in various types of digestive system malignant tumours to provide more valuable information for diagnosing and treating digestive system tumours.

Update on Molecular Imaging and Precision Medicine in Lung Cancer.

Precision medicine integrates molecular pathobiology, genetic make-up, and clinical manifestations of disease in order to classify patients into subgroups for the purposes of predicting treatment response and suggesting outcome. By identifying those patients who are most likely to benefit from a given therapy, interventions can be tailored to avoid the expense and toxicity of futile treatment. Ultimately, the goal is to offer the right treatment, to the right patient, at the right time. Lung cancer is a heterogeneous disease both functionally and morphologically. Further, over time, clonal proliferations of cells may evolve, becoming resistant to specific therapies. PET is a sensitive imaging technique with an important role in the precision medicine algorithm of lung cancer patients. It provides anatomo-functional insight during diagnosis, staging, and restaging of the disease. It is a prognostic biomarker in lung cancer patients that characterizes tumoral heterogeneity, helps predict early response to therapy, and may direct the selection of appropriate treatment.

PET Imaging for Hematologic Malignancies.

Hematologic malignancies are a broad category of cancers arising from the lymphoid and myeloid cell lines. The 2016 World Health Organization classification system incorporated molecular markers as part of the diagnostic criteria and includes more than 100 subtypes. This article focuses on the subtypes for which imaging with positron emission tomography/computed tomography (PET/CT) has become an integral component of the patient's evaluation, that is, lymphoma and multiple myeloma. Leukemia and histiocytic and dendritic cell neoplasms are also discussed as these indications for PET/CT are less common, but increasingly seen in clinic.

PET Imaging for Breast Cancer.

Imaging plays an integral role in the clinical care of patients with breast cancer. This review article focuses on the use of PET imaging for breast cancer, highlighting the clinical indications and limitations of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) PET/CT, the potential use of PET/MRI, and 16α-[18F]fluoroestradiol (FES), a newly approved radiopharmaceutical for estrogen receptor imaging.

18F-FDG-PET/CT Imaging for Gastrointestinal Malignancies.

Gastrointestinal malignancies encompass a variety of primary tumor sites, each with different staging criteria and treatment approaches. In this review we discuss technical aspects of 18F-FDG-PET/CT scanning to optimize information from both the PET and computed tomography components. Specific applications for 18F-FDG-PET/CT are summarized for initial staging and follow-up of the major disease sites, including esophagus, stomach, hepatobiliary system, pancreas, colon, rectum, and anus.

Precision Nuclear Medicine: The Evolving Role of PET in Melanoma.

The clinical management of melanoma patients has been rapidly evolving with the introduction of new targeted immuno-oncology (IO) therapeutics. The current diagnostic paradigms for melanoma patients begins with the histopathologic confirmation of melanoma, initial staging of disease burden with imaging and surgical approaches, treatment monitoring during systemic cytotoxic chemotherapy or IO therapeutics, restaging after completion of adjuvant systemic, surgical, and/or external radiation therapy, and the detection of recurrent malignancy/metastatic disease following therapy. New and evolving imaging approaches with positron-emission tomography (PET) imaging technologies, imaging methodologies, image reconstruction, and image analytics will likely continue to improve tumor detection, tumor characterization, and diagnostic confidence, enabling novel precision nuclear medicine practices for managing melanoma patients. This review will examine current concepts and challenges with existing PET imaging diagnostics for melanoma patients and introduce exciting new opportunities for PET in the current era of IO therapeutics.

PET Imaging for Head and Neck Cancers.

Head and neck cancers are commonly encountered cancers in clinical practice in the United States. Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT has been clinically applied in staging, occult primary tumor detection, treatment planning, response assessment, follow-up, recurrent disease detection, and prognosis prediction in these patients. Alternative PET tracers remain investigational and can provide additional valuable information such as radioresistant tumor hypoxia. The recent introduction of 18F-FDG PET/MR imaging has provided the advantage of combining the superior soft tissue resolution of MR imaging with the functional information provided by 18F-FDG PET. This article is a concise review of recent advances in PET imaging in head and neck cancer.

PET Imaging for Prostate Cancer.

The role of PET imaging with 11C-choline and 18F-fluciclovine in evaluating patients with prostate cancer (PCa) has become more important over the years and has been incorporated into the NCCN guidelines. A new generation of PET radiotracers targeting the prostate-specific membrane antigen (PSMA) is widely used outside the United States to evaluate patients with primary PCa and PCa recurrence. PET imaging influences treatment planning and demonstrates a significantly higher disease detection rate than conventional imaging such as computed tomography and MR imaging. Early data indicate that using PET radiotracers such as 18F-fluciclovine and PSMA improves patient outcomes. 68-Ga-PSMA-11 and 18F-DCFPyL-PET/CT were recently approved by the US Food & Drug Administration (FDA) for clinical use. Other PSMA radiotracers, including fluorinated variants, will likely gain FDA approval in the not-too-distant future.

PET Imaging for Gynecologic Malignancies.

This review article summarizes the clinical applications of established and emerging PET tracers in the evaluation of the 5 most common gynecologic malignancies: endometrial, ovarian, cervical, vaginal, and vulvar cancers. Emphasis is given to 2-deoxy-2-[18F]fluoro-d-glucose as the most widely used and studied tracer, with additional clinical tracers also explored. The common imaging protocols are discussed, including standard dose ranges and uptake times, established roles, as well as the challenges and future directions of these imaging techniques. The key points are emphasized with images from selected cases.

Immune PET Imaging.

Fluorodeoxyglucose (FDG) PET/CT is sensitive to metabolic, immune-related, and structural changes that can occur in tumors in cancer immunotherapy. Unique mechanisms of immune checkpoint inhibitors (ICIs) occasionally make response evaluation challenging, because tumors and inflammatory changes are both FDG avid. These response patterns and sequelae of ICI immunotherapy, such as immune-related adverse events, are discussed. Immune-specific PET imaging probes at preclinical stage or in early clinical trials, which may help guide clinical management of cancer patients treated with immunotherapy and likely have applications outside of oncology for other diseases in which the immune system plays a role, are reviewed.

Longitudinal Changes in Hippocampal Network Connectivity in Alzheimer's Disease.

OBJECTIVE: The hippocampus is connected to 2 distinct cortical brain networks, the posterior-medial and the anterior-temporal networks, involving different medial temporal lobe (MTL) subregions. The aim of this study was to assess the functional alterations of these 2 networks, their changes over time, and links to cognition in Alzheimer's disease. METHODS: We assessed MTL connectivity in 53 amyloid-ß-positive patients with mild cognitive impairment and AD dementia and 68 healthy elderly controls, using resting-state functional magnetic resonance imaging, cross-sectionally and longitudinally. First, we compared the functional connectivity of the posterior-medial and anterior-temporal networks within the control group to highlight their specificities. Second, we compared the connectivity of these networks between groups, and between baseline and 18-month follow-up in patients. Third, we assessed the association in the connectivity changes between the 2 networks, and with cognitive performance. RESULTS: We found decreased connectivity in patients specifically between the hippocampus and the posterior-medial network, together with increased connectivity between several MTL subregions and the anterior-temporal network. Moreover, changes in the posterior-medial and anterior-temporal networks were interrelated such that decreased MTL-posterior-medial connectivity was associated with increased MTL-anterior-temporal connectivity. Finally, both MTL-posterior-medial decrease and MTL-anterior-temporal increase predicted cognitive decline. INTERPRETATION: Our findings demonstrate that longitudinal connectivity changes in the posterior-medial and anterior-temporal hippocampal networks are linked together and that they both contribute to cognitive decline in Alzheimer's disease. These results shed light on the critical role of the posterior-medial and anterior-temporal networks in Alzheimer's disease pathophysiology and clinical symptoms. ANN NEUROL 2021;90:391-406.

Why is it important to report early possible COVID-19 PET/CT findings in cancer patients? Explaining with a case series.

BACKGROUND: Coronavirus disease-2019 (COVID-19) causing a pandemic mostly results in mild symptoms; however, it can evolve into serious complications. It is emphasized that if the term from the recent anticancer treatment to the diagnosis of COVID-19 was short, the probability of serious events increased in cancer patients. Therefore, early detection of COVID-19 and prevention of serious events is very important. We aimed to investigate whether it is possible to detect COVID-19 early by positron emission tomography (PET)/computed tomography (CT). METHODS: We retrospectively evaluated the images and clinical findings of patients who underwent PET/CT due to malignancy and whose COVID-19 polymerase chain reaction (PCR) test were detected positive subsequently. RESULTS: Eight cancer patients with positive COVID-19 PCR tests were included in the study. PET/CT revealed subpleural ground-glass opacities (GGOs) showing mild fluorodeoxyglucose (FDG) uptake that could be compatible with COVID-19 in 4 of 8 patients. The number of affected lobes ranged from 1-4. All patients were diagnosed with COVID-19 by PCR test when symptoms and/or lung findings worsened on the days after PET/CT. The time interval between the last anticancer treatment and COVID-19 diagnosis in five patients was ≤7 days. During the follow-up, six of the cases (75%) needed mechanical ventilation and died later. CONCLUSION: COVID-19 may be recognised early by detecting incidental findings in PET/CT, especially in asymptomatic cancer patients. Potential complications may be prevented by early diagnosis and anticancer therapy changes. Therefore, possible COVID-19 findings in PET/CT should be reported and the patient should be referred to relevant clinician.

Quantitative PET in the 2020s: a roadmap.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET. Despite impressive improvements in image quality as a result of these advances, the emphasis on static, semi-quantitative 'hot spot' imaging for oncologic applications has meant that the capability of PET to quantify biologically relevant parameters based on tracer kinetics has not been fully exploited. More recent advances, such as PET/MR and total-body PET, have opened up the ability to address a vast range of new research questions, from which a future expansion of applications and radiotracers appears highly likely. Many of these new applications and tracers will, at least initially, require quantitative analyses that more fully exploit the exquisite sensitivity of PET and the tracer principle on which it is based. It is also expected that they will require more sophisticated quantitative analysis methods than those that are currently available. At the same time, artificial intelligence is revolutionizing data analysis and impacting the relationship between the statistical quality of the acquired data and the information we can extract from the data. In this roadmap, leaders of the key sub-disciplines of the field identify the challenges and opportunities to be addressed over the next ten years that will enable PET to realise its full quantitative potential, initially in research laboratories and, ultimately, in clinical practice.

Current practice in patients with differentiated thyroid cancer.

Considerable changes have occurred in the management of differentiated thyroid cancer (DTC) during the past four decades, based on improved knowledge of the biology of DTC and on advances in therapy, including surgery, the use of radioactive iodine (radioiodine), thyroid hormone treatment and availability of recombinant human TSH. Improved diagnostic tools are available, including determining serum levels of thyroglobulin, neck ultrasonography, imaging (CT, MRI, SPECT-CT and PET-CT), and prognostic classifications have been improved. Patients with low-risk DTC, in whom the risk of thyroid cancer death is <1% and most recurrences can be cured, currently represent the majority of patients. By contrast, patients with high-risk DTC represent 5-10% of all patients. Most thyroid cancer-related deaths occur in this group of patients and recurrences are frequent. Patients with high-risk DTC require more aggressive treatment and follow-up than patients with low-risk DTC. Finally, the strategy for treating patients with intermediate-risk DTC is frequently defined on a case-by-case basis. Prospective trials are needed in well-selected patients with DTC to demonstrate the extent to which treatment and follow-up can be limited without increasing the risk of recurrence and thyroid cancer-related death.

Added value of 18F-FDG-PET/CT and cardiac CTA in suspected transcatheter aortic valve endocarditis.

BACKGROUNDS: Transcatheter-implanted aortic valve infective endocarditis (TAVI-IE) is difficult to diagnose when relying on the Duke Criteria. Our aim was to assess the additional diagnostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) in suspected TAVI-IE. METHODS: A multicenter retrospective analysis was performed in all patients who underwent 18F-FDG-PET/CT and/or CTA with suspected TAVI-IE. Patients were first classified with Duke Criteria and after adding 18F-FDG-PET/CT and CTA, they were classified with European Society of Cardiology (ESC) criteria. The final diagnosis was determined by our Endocarditis Team based on ESC guideline recommendations. RESULTS: Thirty patients with suspected TAVI-IE were included. 18F-FDG-PET/CT was performed in all patients and Cardiac CTA in 14/30. Using the Modified Duke Criteria, patients were classified as 3% rejected (1/30), 73% possible (22/30), and 23% definite (7/30) TAVI-IE. Adding 18F-FDG-PET/CT and CTA supported the reclassification of 10 of the 22 possible cases as "definite TAVI-IE" (5/22) or "rejected TAVI-IE" (5/22). This changed the final diagnosis to 20% rejected (6/30), 40% possible (12/30), and 40% definite (12/30) TAVI-IE. CONCLUSIONS: Addition of 18F-FDG-PET/CT and/or CTA changed the final diagnosis in 33% of patients and proved to be a valuable diagnostic tool in patients with suspected TAVI-IE.

Prostate-Specific Membrane Antigen-Targeted Radiopharmaceuticals in Diagnosis and Therapy of Prostate Cancer: Current Status and Future Perspectives.

Prostate cancer is the most common cancer to affect men in the United States and the second most common cancer in men worldwide. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging has become increasingly popular as a novel molecular imaging technique capable of improving the clinical management of patients with prostate cancer. To date, several 68Ga and 18F-labeled PSMA-targeted molecules have shown promising results in imaging patients with recurrent prostate cancer using PET/computed tomography (PET/CT). Studies of involving PSMA-targeted radiopharmaceuticals also suggest a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and methylene diphosphonate bone scintigraphy) and 11C/18F-choline PET/CT. In addition, PSMA-617 and PSMA I&T ligands can be labeled with α- and ß-emitters (e.g., 225Ac, 90Y, and 177Lu) and serve as a theranostic tool for patients with metastatic prostate cancer. While the clinical impact of such concept remains to be verified, the preliminary results of PSMA molecular radiotherapy are very encouraging. Herein, we highlighted the current status of development and future perspectives of PSMA-targeted radiopharmaceuticals and their clinical applications.

Where to next prostate-specific membrane antigen PET imaging frontiers?

PURPOSE OF REVIEW: Technical improvements in imaging equipment and availability of radiotracers, such as PSMA-ligands have increased the synergy between Urology and Nuclear Medicine. Meanwhile artificial intelligence is introduced in Nuclear Imaging. This review will give an overview of recent technical and clinical developments and an outlook on application of these in the near future. RECENT FINDINGS: Digital PET/CT has shown gradual improvement in lesion detection and demarcation over conventional PET/CT, but total-body PET/CT holds promise for a magnitude of improvement in scan duration and quality, quantification, and dose optimization. PET-guided decision-making with the application of PSMA-ligands has been shown useful in demonstrating and biopting primary prostate cancer (PCa) lesions, guiding radiotherapy, guiding surgical resection of recurrent PCa, and assessing therapy response in PCa. Artificial intelligence made its way into Nuclear Imaging just recently, but encouraging progress promises clinical application with unprecedented possibilities. SUMMARY: Evidence is growing on clinical usefulness of PET-guided decision-making with the still relatively new PSMA ligands as a prime example. Rapid evolution of PET instrumentation and clinical introduction of artificial intelligence will be the gamechangers of nuclear imaging in the near future, though its powers should still be mastered and incorporated in clinical practice.

Total-Body PET/CT: Current Applications and Future Perspectives.

OBJECTIVE. The purpose of this article is to describe the clinical applications of a total-body PET scanner and discuss future expectations. CONCLUSION. PET has been widely used in the fields of oncology, neurology, and cardiology. However, current PET scanners have limitations, including long scanning time, low signal-to-noise ratio, and high dose of ionizing radiation. Total-body PET with a long scan range provides solutions to these problems, markedly increasing the sensitivity of the system.