Non-18F-FDG/18F-NaF radiotracers proposed for the diagnosis and management of diseases of the heart and vasculature

18F-FDG and 18F-NaF have been used extensively in the identification of various cardiovascular diseases, but not without limitations. Several other PET radiotracers have been identified as possible markers for cardiovascular-associated inflammation and infection. Non-18F-FDG/18F-NaF molecules may have utility as alternative radiotracers in the detection and management of cardiovascular diseases, but few have demonstrated clinical value

Novel musculoskeletal and orthopedic applications of 18F-sodium fluoride PET

Key points 18F-sodium fluoride (NaF) PET can detect causes of bone pain and traumatic injuries that cannot be successfully visualized by other modalities such as radiography, bone scintigraphy, computed tomography, and magnetic resonance. Thus, NaF-PET may contribute to the assessment of occult fractures, child abuse, and stress-related injuries. NaF-PET is an excellent modality to assess osteoarthritis, ankylosing spondylitis, and temporomandibular joint dysfunction. More studies are needed to determine its potential role in inflammatory arthropathies such as rheumatoid arthritis and psoriatic arthritis. Complications of orthopedic surgery such as hardware loosening and infection are readily visualized by NaF-PET. Heterotopic ossification after surgery is another possible imaging target that requires further exploration. Metabolic bone diseases such as osteoporosis and Paget disease can be evaluated over time with NaF-PET to determine effects of pharmacologic interventions such as bisphosphonates and teriparatide. NaF-PET may have a role in assessing primary bone tumors such as osteosarcoma, helping to determine response to treatment and guiding patient management decisions

A critical review of PET tracers used for brain tumor imaging

Because enhancement on computed tomography (CT) and MR reflects blood-brain barrier (BBB) changes, molecular imaging with PET-based techniques is needed to assess brain tumor activity, especially in tumors with intact or partially intact BBB. 18F-fluorodeoxyglucose (FDG)-PET has been validated in tumor detection/delineation, recurrence, and prognostication. Although FDG remains the most widely used PET tracer in the evaluation of brain tumors, various other tracers, including amino acid indicators, have been studied extensively. Breakdown of the BBB plays a major role in visualizing brain tumors by radiolabeled amino acid tracers; therefore, this approach is suboptimal for assessing disease activity beyond CT and MR

Utility of FDG-PET/CT in clinical psoriasis grading: the PET-PASI scoring system

Psoriatic skin lesions are metabolically active, which makes them candidates for imaging with 18-F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The aim of our study was to correlate FDG-PET findings with Psoriasis Area and Severity Index (PASI) scores, the most widely-used grading system for psoriasis. Thirty-three subjects and a total of 84 FDG-PET/CT scans from a prospective clinical trial [NCT01553058] with >2 months moderate-to-severe psoriasis were included. Subjects underwent whole-body FDG-PET/CT imaging 60 min after intravenous FDG administration, prior to the start of treatment. Scans were repeated 12 weeks and 52 weeks after baseline scans were conducted and after treatment or placebo administration was initiated. Each subject and scan was graded by our “PET-PASI” scoring system, a qualitative review of multi-plane reconstructions for both attenuation-corrected (AC) and non-attenuation-corrected (NAC) PET images. PASI and PET-PASI scores were correlated using Spearman’s rho analysis. Our study demonstrated a significant positive correlation between each subject’s corresponding PET-PASI and PASI scores before and during treatment or placebo administration (r=0.53, P<0.001). We also found positive correlations between PET-PASI and PASI scores across different regions of the body (head and neck: r=0.22, upper extremities: r=0.26, trunk: r=0.48, and lower extremities: r=0.58). In conclusion, AC and NAC FDG-PET/CT images may be utilized to evaluate lesions in subjects with moderate-to-severe psoriasis. Our methodology could have future implications in the diagnosis and therapeutic management of psoriasis

18F-FDG-PET/CT in radiation therapy-induced parotid gland inflammation

Background 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is used in the clinical management of oncologic and inflammatory pathologies. It may have utility in detecting radiotherapy (RT)-induced damage of oral tissues. Thus, the aim of the present study was to use FDG-PET/CT to evaluate parotid gland inflammation following RT in patients with head and neck cancer (HNC). Methods This retrospective study included patients with HNC treated with photon, proton, or combined photon/proton RT, in addition to chemotherapy. All patients received FDG-PET/CT imaging pre-treatment and 3 months post-treatment. The average mean standardized uptake value (Avg SUVmean) and the average maximum standardized uptake value (Avg SUVmax) of the left and right parotid glands were determined by global assessment of FDG activity using OsiriX MD software. A two-tailed paired t test was used to compare Avg SUVmean and Avg SUVmax pre- and post-RT. Results Forty-seven HNC patients were included in the study. Parotid gland Avg SUVmean was significantly higher at 3 months post-treatment than pre-treatment (p < 0.05) in patients treated with photon RT, but no significant differences were found between pre- and post-treatment Avg SUVmean in patients treated with proton RT or combined photon/proton RT. Conclusion Our results suggest that photon RT may cause radiation-induced inflammation of the parotid gland, and that proton RT, which distributes less off-target radiation, is a safer treatment alternative

Imaging atherosclerosis by PET, with emphasis on the role of FDG and NaF as potential biomarkers for this disorder

Molecular imaging has emerged in the past few decades as a novel means to investigate atherosclerosis. From a pathophysiological perspective, atherosclerosis is characterized by microscopic inflammation and microcalcification that precede the characteristic plaque buildup in arterial walls detected by traditional assessment methods, including anatomic imaging modalities. These processes of inflammation and microcalcification are, therefore, prime targets for molecular detection of atherosclerotic disease burden. Imaging with positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) can non-invasively assess arterial inflammation and microcalcification, respectively. FDG uptake reflects glucose metabolism, which is particularly increased in atherosclerotic plaques retaining macrophages and undergoing hypoxic stress. By contrast, NaF uptake reflects the exchange of hydroxyl groups of hydroxyapatite crystals for fluoride producing fluorapatite, a key biochemical step in calcification of atherosclerotic plaque. Here we review the existing literature on FDG and NaF imaging and their respective values in investigating the progression of atherosclerotic disease. Based on the large volume of data that have been introduced to the literature and discussed in this review, it is clear that PET imaging will have a major role to play in assessing atherosclerosis in the major and coronary arteries. However, it is difficult to draw definitive conclusions on the potential role of FDG in investigating atherosclerosis given the vast number of studies with different designs, image acquisition methods, analyses, and interpretations. Our experience in this domain of research has suggested that NaF may be the tool of choice over FDG in assessing atherosclerosis, especially in the setting of coronary artery disease (CAD). Specifically, global NaF assessment appears to be superior in detecting plaques in tissues with high background FDG activity, such as the coronary arteries

18F-FDG-PET/CT in the quantification of photon radiation therapy-induced vasculitis

Radiation therapy (RT) is an important component of care for head and neck cancers (HNC). Photon RT vasculitis is a complication of incidental dose delivery to nearby vascular structures. However, optimal methods for early diagnosis are not clearly established. The aim of this study was to evaluate 18F-FDG-PET/CT in detecting radiation-induced vasculitis of the left common carotid (LCC) and the arch of the aorta (AoA) in patients treated for HNC. 18F-FDG-PET/CT scans obtained before RT (Pre-RT) and 3 months after RT (Post-RT) were retrospectively reviewed in 30 HNC patients (25 males, 5 females; average age 57.9±8.1 years) treated with photon RT. All subjects underwent 18F-FDG-PET/CT imaging 60 minutes after 5.0 MBq/kg 18F-FDG injection. Average standard uptake values (Avg SUVmean) of the LCC and AoA were obtained by global assessment. A two-tailed paired t-test was used to assess the difference in Avg SUVmean between pre- and post-RT imaging. Subjects demonstrated significant increased Avg SUVmean within the LCC post-RT (pre = 1.42, post = 1.65, P<0.001), with a mean increase of 0.23 SUV. Similarly, subjects exhibited higher 18F-FDG uptake in the AoA post-RT (pre = 1.44, post = 1.69, P<0.01), with a mean increase of 0.23 SUV. 18F-FDG-PET/CT may be used to detect and quantify photon RT vasculitis in HNC patients. Further investigation is warranted to evaluate the clinical implications of this pathology and the role for alternative treatment strategies in minimizing tissue toxicity

Venous thromboembolism detected by FDG-PET/CT in cancer patients: a common, yet life-threatening observation

Cancer patients are at markedly increased risk for venous thromboembolism (VTE). Early detection of VTE may decrease morbidity and mortality in this population. We conducted this study to evaluate the ability of FDG-PET/CT to detect thrombosis in cancer patients. This retrospective study included 131 cancer patients with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) referred for 2-deoxy-2-[18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT). All subjects underwent PET/CT imaging 60 minutes after FDG injection. Images were visually assessed for increased FDG uptake within the venous lumen. For positive cases, clinical follow-up and Doppler ultrasonography and/or contrast-enhanced CT scans were reviewed. FDG-PET/CT revealed abnormal uptake in the venous system of 26 (19.8%) patients. Eighteen (69.2%) had a history of DVT, and 13 (50%) had a history of PE. The most common site of thrombosis was the inferior vena cava (IVC) (n=14, 53.8%), followed by lower extremities veins (n=9, 34.6%), jugular veins (n=2, 7.7%), and superior vena cava (n=1, 3.8%). The presence of thrombi was confirmed by reviewing clinical follow-up in 6 (23.1%) patients. Among this group, thrombosis was detected in lower extremity veins (n=4, 15.8%), jugular veins (n=1, 3.8%), and IVC (n=1, 3.8%). Our study demonstrates that thrombi prior to their clinical manifestation can be detected by FDG-PET/CT in cancer patients. Moving forward, physicians must carefully consider the venous system when reporting FDG-PET/CT for cancer patients

Implementation of FDG-PET/CT imaging methodology for quantification of inflammatory response in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (