Comparison of 18F-sodium fluoride uptake in the whole bone, pelvis, and femoral neck of multiple myeloma patients before and after high-dose therapy and conventional-dose chemotherapy.

AIM: To compare the effects of high-dose therapy (HDT consisting of high-dose chemotherapy followed by autologous stem cell transplantation) and conventional-dose chemotherapy (non-HDT) on the uptake of 18F-sodium fluoride (NaF) in the whole bone, pelvis, and femoral neck of multiple myeloma (MM) patients. METHOD: The data of 19 MM patients who received HDT (61.5 (SD 5.6) years) and 11 MM patients who received conventional-dose chemotherapy (70.9 (SD 7.2) years) were collected in a prospective study. NaF PET/CT imaging was performed at baseline, and 8 weeks and 2 weeks after treatment for the HDT group and the non-HDT group, respectively. A CT-based algorithm was applied to segment the bones, and the global mean SUV (GSUVmean) of the whole bone and pelvis was calculated (OsiriX MD v.9.0, Pixmeo SARL; Bernex, Switzerland). In addition, regions of interest for the whole, medial, and lateral femoral neck were delineated bilaterally. Whole bone and pelvis measurements were replicated by two observers. RESULTS: The average GSUVmean in the whole bone and pelvis of the patients who underwent HDT significantly decreased from before to after treatment (- 16.27%, p = 0.02 and - 16.54%, p = 0.01, respectively). A significant decrease in the whole and lateral femoral neck was also observed bilaterally in the HDT group. No significant decrease in average GSUVmean was observed in the non-HDT group. A high level of inter-observer reliability was found in intra-class correlation (ICC for pre-treatment whole bone 0.983, post-treatment whole bone 0.989, pre-treatment whole pelvis 0.998, post-treatment whole pelvis 0.996). CONCLUSION: NaF uptake significantly decreased after treatment in patients who received high-dose therapy. A high level of agreement was observed between two operators for whole bone and pelvis measurements.

Assessing Coronary Artery and Aortic Calcification in Patients with Prostate Cancer Using 18F-Sodium Fluoride PET/Computed Tomography.

The aim of this study was to assess coronary artery and aortic calcification in healthy controls, angina pectoris patients, and prostate cancer patients using 18F-sodium fluoride PET/computed tomography (NaF-PET/CT). A retrospective analysis compared 33 prostate cancer patients with 33 healthy subjects and 33 patients with angina pectoris. Increased target-to-background ratio (TBR) of the coronary arteries, ascending aorta, aortic arch, and descending aorta was observed in cancer patients compared to healthy controls but not compared to angina pectoris patients. These results demonstrate the feasibility of assessing vascular microcalcification with NaF-PET/CT, with significant differences in uptake according to comorbidities.

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 (P<0.0001 and P=0.004). Absolute increases in PVC-SUVmean and PVC-GLPG were more pronounced (ΔPVC-SUVmean 0.32 versus ΔSUVmean 0.28; ΔPVC-GLPG 463.34 cc versus ΔGLPG 352.90 cc) and highly significant (P<0.0001). In contrast, the contralateral lung demonstrated no significant difference between pre-RT to post-RT in either GLPG (P=0.12) or SUVmean (P=0.18). The only clinical feature significantly associated with post-RT PET/CT parameters was clinical staging. Our study demonstrated inflammatory response in the ipsilateral lung of NSCLC patients treated with photon RT, suggesting that PET/CT parameters may serve as biomarkers for radiation pneumonitis (RP).

18F-NaF Uptake in Ocular Prosthesis (Implant).

Ocular prosthesis is used as a replacement in the orbit following enucleation or evisceration of the eye. Polymethyl methacrylate (PMMA), hydroxyapatite (HA) and porous polyethylene (PP) are some examples of the materials used in ocular prosthesis. We present a case of an 82-year-old man with prostate cancer who underwent F-NaF PET/CT imaging for evaluation of bone metastases and was incidentally found to have increased NaF uptake in the ocular prosthesis.

Novel Quantitative PET Imaging Techniques in Tuberculosis.

The role of fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in tuberculosis (TB) continues to expand in disease detection, assessment of the extent of the disease, and treatment response monitoring. This article reviews available data regarding the use of FDG-PET/CT in patients with TB. A new method of quantification for patients with TB is introduced. This method produces robust parameters that represent the total disease burden.

Comparison of atherosclerotic burden in non-lower extremity arteries in patients with and without peripheral artery disease using 18F-NaF-PET/CT imaging.

Atherosclerosis is the most common cause of peripheral artery disease (PAD). We compared the atherosclerotic burden in non-lower extremity arteries in patients with and without PAD using 18F-sodium fluoride (NaF)-PET/CT. We identified five individuals (61.8±6.6 years, one male, four females) with PAD and matched to five individuals without PAD based on age and gender from the unfavorable cardiovascular risk profile group of the CAMONA trial (60±7.2 years, one male, four females). Individuals underwent PET/CT imaging 90 minutes after the injection of NaF (2.2 Mbq/Kg). CT imaging was conducted to account for attenuation correction and anatomic referencing. The NaF uptake was measured by manually defining regions of interest on each axial slice on the following arteries: coronary artery (CA), carotid artery (CR), ascending aorta (AS), arch of aorta (AR), descending aorta (DA), and abdominal aorta (AA). Average SUVmean (aSUVmean) was calculated for each segment. Wilcoxon's signed rank test was used for statistical analysis. The total aSUVmean was higher in the PAD group compared to the non-PAD group (6.54±0.9 vs. 5.03±0.45, P=0.043). Comparison revealed higher NaF uptake in CR, AS, AR, and DA in the PAD group compared to the non-PAD group (0.93±0.25 vs. 0.54±0.14, P=0.01; 1.28±0.20 vs. 0.86±1.19, P<0.01; 1.18±0.17 vs. 0.90±0.19, P=0.03; 1.32±0.24 vs. 0.91±0.15, P=0.01). The NaF uptake in CA and AA was similar between the two groups (0.77±0.04 vs. 0.71±0.05, P=0.11; 1.07±0.28 vs. 1.12±0.30, P=0.82). We found individuals with PAD had higher atherosclerotic burden in the carotid arteries and thoracic aorta compared to non-PAD subjects.

Diagnosis and Monitoring of Osteoporosis with Total-Body 18F-Sodium Fluoride-PET/CT.

In recent years, 18F-Sodium Fluoride (NaF)-PET/CT has seen its role in the detection and management of osteoporosis increase. This article reviews the extent of this application in the literature, its efficacy compared with other comparable imaging tools, and how total-body PET/CT combined with global disease assessment can revolutionize measurement of total osteoporotic disease activity. NaF-PET/CT eventually can be the modality of choice for metabolic bone disorders, especially with these advances in technology and computation.

Prognostic significance of 18F-sodium fluoride in newly diagnosed multiple myeloma patients.

Focal bone lesions and fractures due to weakened bone are associated with higher morbidity and mortality of multiple myeloma (MM) patients. 18F-sodium fluoride (18F-NaF) is a sensitive PET radiotracer for detection of abnormal bone metabolism and, therefore, is particularly suited to assess the degree of bone involvement in MM patients. We aimed to investigate the prognostic significance of metabolic active volume (MAV) of 18F-NaF-avid lesions in MM patients. In addition to MAV, conventional methods of PET quantification, namely SUVmean and SUVmax, were measured in each patient for the purpose of comparison. Thirty-seven newly diagnosed MM patients were included. PET imaging was performed after intravenous administration of 200 MBq NaF. Active bone lesions and fractures on whole-body 18F-NaF-PET/CT scans were identified. An adaptive thresholding algorithm automatically calculated the total MAV, SUVmean and SUVmax for each patient (ROVER, ABX, Radeberg, Germany). The patients were followed for a median of 39.8 months after treatment (range: 17.8-55.4). The overall survival (OS) of patients with 18F-NaF-MAV value > 38.65 (36.36% [N of Events/Total N: 4/11]) was significantly shorter than that of patients with 18F-NaF-MAV value < 38.65 (3.85% [1/26]; P = 0.002). In multivariate forward stepwise (conditional LR) Cox regression analysis of prognostic factors of OS (including 18F-NaF-MAV (> 38.65 or < 38.65), age, gender, beta-2 microglobulin, and revised international staging system), 18F-NaF-MAV remained the only significant factor (HR: 14.39, P = 0.02). The results for PFS were not significant. Moreover, Kaplan-Meier analyses of conventional methods of PET quantification did not reveal any statistically significant log-rank p-values. MM patients with high 18F-NaF-MAV had shorter overall survival, compared to those with low 18F-NaF-MAV levels (NCT02187731).

Assessing the feasibility of NaF-PET/CT versus FDG-PET/CT to detect abdominal aortic calcification or inflammation in rheumatoid arthritis patients.

OBJECTIVE: We aimed to determine whether NaF-PET/CT or FDG-PET/CT can detect abdominal aortic molecular calcification and inflammation in patients with rheumatoid arthritis (RA). METHODS: In this study, 18 RA patients (4 women, 14 men; mean age 56.0 ± 11.7) and 18 healthy controls (4 women, 14 men; mean age 55.8 ± 11.9) were included. The controls were matched to patients by sex and age (± 4 years). All subjects of this study underwent NaF-PET/CT scanning 90 min following the administration of NaF. FDG-PET/CT imaging was performed 180 min following intravenous FDG injection. Using OsiriX software, the global mean standardized uptake value (global SUVmean) in abdominal aorta was calculated for both FDG and NaF. The NaF SUVmean and FDG SUVmean were divided by the blood pool activity providing target-to-background ratios (TBR) namely, NaF-TBRmean and FDG-TBRmean. The CT calcium volume score was obtained using a growing region algorithm based on Hounsfield units. RESULTS: The average NaF-TBRmean score among RA patients was significantly greater than that of healthy controls (median 1.61; IQR 1.49-1.88 and median 1.40; IQR 1.23-1.52, P = 0.002). The average CT calcium volume score among RA patients was also significantly greater than that of healthy controls (median 1.96 cm3; IQR 0.57-5.48 and median 0.004 cm3; IQR 0.04-0.05, P < 0.001). There was no significant difference between the average FDG-TBRmean scores in the RA patients when compared to healthy controls (median 1.29; IQR 1.13-1.52 and median 1.29; IQR 1.13-1.52, respectively, P = 0.98). CONCLUSION: Quantitative assessment with NaF-PET/CT identifies increased molecular calcification in the wall of the abdominal aorta among patients with RA as compared with healthy controls, while quantitative assessment with FDG-PET/CT did not identify a difference in aortic vessel wall FDG uptake between the RA and healthy control groups.

PET Assessment of Immune Effects from Interventional Oncology Procedures.

Interventional oncology treatments have profound effects on tumor immunity. Quantitative molecular imaging with FDG-PET has the potential to aid in understanding baseline tumor characteristics that can predict response to interventional oncology treatments and immunotherapy. This review highlights some of the evidence for immune activation in the setting of locoregional therapies, and the patterns of treatment response that may be expected in the setting of immune induction. Also presented is an argument for measuring global disease metabolic activity over conventional methods of PET quantitation to circumvent challenges in correlating conventional methods of PET quantification to overall disease activity.

Metastatic Seeding Attacks Bone Marrow, Not Bone: Rectifying Ongoing Misconceptions.

Conventional modalities, such as bone scintigraphy, are commonly used to assess osseous abnormalities in skeletal metastasis. Fluorine-18 (18F)-sodium fluoride (NaF) PET similarly portrays osteoblastic activity but with improved spatial and contrast resolution and more accurate anatomic localization. However, these modalities rely on indirect evidence for tumor activity. PET imaging with 18F-fluorodeoxyglucose (FDG) and tumor-specific tracers may have an increased role by directly portraying the metabolic activity of cancer cells, which are often seeded in bone marrow and cause osseous disease after initial latency. This article describes the utility and limitations of these modalities in assessing skeletal metastases.

Identification of Heterotopic Ossification Using 18F-NaF PET/CT.

Heterotopic ossification (HO) is a benign condition characterized by the abnormal formation of mature lamellar bone in extraskeletal soft tissues. Most frequently, HO is observed around the hip joint after fractures or surgical procedures such as open reduction internal fixation or total hip arthroplasties. We are presenting a case of HO as detected by F-NaF PET/CT in a 68-year-old woman with multiple myeloma and a history of internal fixation of the right hip. Many previous publications have reported F-NaF uptake portraying calcification in soft tissue; the present report demonstrates the feasibility of F-NaF PET/CT to assess extraosseous calcification.

The Evolving Role of PET-Based Novel Quantitative Techniques in the Interventional Radiology Procedures of the Liver.

Interventional radiology procedures have revolutionized the treatment of cancer and interventional oncology is now the fourth pillar of cancer care. The article discusses the importance of fluorodeoxyglucose (FDG)-PET imaging, and dual time-point imaging in the context of PET/computed tomography as applied to treatments of liver malignancy. The necessary paradigm shift in the adoption of novel segmentation methodologies to express global disease burden is explored.

The Evolving Role of FDG-PET/CT in the Diagnosis, Staging, and Treatment of Breast Cancer.

The applications of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (PET/CT) in the management of patients with breast cancer have been extensively studied. According to these studies, PET/CT is not routinely performed for the diagnosis of primary breast cancer, although PET/CT in specific subtypes of breast cancer correlates with histopathologic features of the primary tumor. PET/CT can detect metastases to mediastinal, axial, and internal mammary nodes, but it cannot replace the sentinel node biopsy. In detection of distant metastases, this imaging tool may have a better accuracy in detecting lytic bone metastases compared to bone scintigraphy. Thus, PET/CT is recommended when advanced-stage disease is suspected, and conventional modalities are inconclusive. Also, PET/CT has a high sensitivity and specificity to detect loco-regional recurrence and is recommended in asymptomatic patients with rising tumor markers. Numerous studies support the future role of PET/CT in prediction of response to neoadjuvant chemotherapy (NAC). PET/CT has a higher diagnostic value for prognostic risk stratification in comparison with conventional modalities. With the continuing research on the treatment planning and evaluation of patients with breast cancer, the role of PET/CT can be further extended.

Evolving Roles of Fluorodeoxyglucose and Sodium Fluoride in Assessment of Multiple Myeloma Patients: Introducing a Novel Method of PET Quantification to Overcome Shortcomings of the Existing Approaches.

PET with fluorodeoxyglucose and sodium fluoride (NaF) radiotracers has shown a great promise in assessing patients with multiple myeloma (MM). However, the standardization of PET/computed tomography scans interpretation in patients with myeloma in clinical practice is still debatable. This article reviews available data regarding the use of fluorodeoxyglucose and NaF PET in patients with MM. Introduced is a novel method of PET quantification as applied to patients with MM. A new concept for PET-based evaluation of patients with MM is also discussed: dual time point imaging. Finally, the role of NaF in assessment of cardiovascular complications of MM is described.

Pretreatment volumetric parameters of FDG-PET predict the survival after Yttrium-90 radio-embolization in metastatic liver disease.

This study aimed to determine the prognostic value of pretreatment FDG-PET in patients with metastatic liver disease undergoing Yttrium 90 (90Y) radio-embolization using global disease assessment measures. Data from 16 patients with metastatic liver disease (8 males, 8 females) aged 55-97 years (mean: 67±12) were retrospectively collected. On PET, active malignant lesions in the liver were segmented with an adaptive thresholding system (ROVER software, ABX GmbH, Radeberg, Germany). Conventional measures of PET quantification such as SUVmean, SUVmax, and partial volume-corrected SUVmean (pvcSUVmean) and volumetric parameters including metabolic tumor volume (MTV), total lesion glycolysis (TLG) and pvcTLG were measured. Receiver operating characteristic (ROC) was used to determine the optimal cutoffs for Kaplan-Meier analyses. Kaplan-Meier analysis was performed to estimate progression-free survival (PFS) and overall survival (OS). In addition, Cox regression analysis was used to determine predictors of PFS and OS. There was no correlation between pretreatment conventional parameters of FDG-PET and PFS or OS. In contrast, in the univariate Cox regression analyses, pretreatment volumetric parameters were significant predictors for PFS [TLG (HR: 6.1, P=0.02), pvcTLG (HR: 3.9, P=0.03) and MTV (HR: 5.8, P=0.02)]. Moreover, TLG (HR: 6.1, P=0.03), pvcTLG (HR: 5.2, P<0.01) and MTV (HR: 10.7, P<0.01) were significant prognostic factors for OS. Pretreatment volumetric FDG-PET parameters are prognostic factors for PFS and OS in patients with liver metastasis receiving radio-embolization with 90Y.

Dynamics of fluorine-18-fluorodeoxyglucose uptake in the liver and its correlation with hepatic fat content and BMI.

PURPOSE: The aim of this study was to explore the rate of elimination of fluorine-18-fluorodeoxyglucose (F-FDG) from the liver and assess the impact of hepatic fat and obesity on F-FDG clearance in early and delayed PET scans. We hypothesized that an increase in liver fat may cause a decline in hepatic F-FDG elimination with potential consequences as measured by dual time-point F-FDG PET/CT imaging. PATIENTS AND METHODS: A total of 32 patients from the Cardiovascular Molecular Calcification Assessed by F-NaF PET/CT (CAMONA) clinical trial (17 males, 15 females; mean age: 47.2 years, range: 23-69 years, mean BMI: 27.2 kg/m) were enrolled and underwent F-FDG PET/CT 90 and 180 min after tracer injection. Global mean standardized uptake value (SUVmean) (i.e. the average of SUVmean in segmented liver slices) and average maximum standardized uptake value (SUVmax) (i.e. the average of the SUVmax values recorded in same slices) were calculated for semiquantification of liver F-FDG uptake at both time-points. Percentage difference in global SUVmean and average SUVmax were also calculated to yield respective retention indices (RImean and RImax). Changes in global SUVmean, average SUVmax, RImean, and RImax from 90 to 180 min were correlated with BMI and liver fat content as measured by CT Hounsfield units. RESULTS: There was a 12.2±3.5 percent reduction in global liver SUVmean and a 4.1±5.8 percent reduction in average SUVmax at 180 min scan as compared with the 90 min time-point. RImean and RImax were inversely correlated with liver fat content and positively correlated with BMI. CONCLUSION: We observed a time-dependent decrease in global hepatic SUVmean and average SUVmax, which was affected by the amount of liver fat. Patients with higher BMI and hepatic fat content tended to retain F-FDG.