Detection of Biochemically Recurrent Prostate Cancer with [18F]DCFPyL PET/CT: An Updated Systematic Review and Meta-Analysis with a Focus on Correlations with Serum Prostate-Specific Antigen Parameters.

[18F]DCFPyL is increasingly used for prostate-specific membrane antigen (PSMA) mediated imaging of men with biochemically recurrent prostate cancer (BRPCa). In this meta-analysis, which is updated with the addition of multiple new studies, including the definitive phase III CONDOR trial, we discuss the detection efficiency of [18F]DCFPyL in BRPCa patients. PubMed was searched on 29 September 2022. Studies evaluating the diagnostic performance of [18F]DCFPyL among patients with BRPCa were included. The overall pooled detection rate with a 95% confidence interval (95% CI) was calculated among all included studies and stratified among patients with PSA ≥ 2 vs. <2 ng/mL and with PSA ≥ 0.5 vs. <0.5 ng/mL. The association of detection efficiency with pooled PSA doubling time from two studies was calculated. Seventeen manuscripts, including 2252 patients, met the inclusion criteria and were used for data extraction. A previous meta-analysis reported that the pooled detection rate was 0.81 (95% CI: 0.77-0.85), while our study showed a pooled overall detection rate of 0.73 (95% CI: 0.66-0.79). An increased proportion of positive scans were found in patients with PSA ≥ 2 vs. <2 ng/mL and PSA ≥ 0.5 vs. <0.5 ng/mL. No significant difference was found in detection efficiency between those with PSA doubling time ≥ 12 vs. <12 months. Detection efficiency is statistically related to serum PSA levels but not to PSA doubling time based on available data. The detection efficiency of [18F]DCFPyL in men with BRPCa has trended down since a previous meta-analysis, which may reflect increasingly stringent inclusion criteria for studies over time.

Sarcopenia and Myositis Revisited: Emerging Role of Fluorine-18 Fluorodeoxyglucose PET in Muscle Imaging.

Fluorodeoxyglucose (FDG) PET/computed tomography (CT) is a valuable diagnostic modality in the work-up of patients with suspected inflammatory myopathy. Sarcopenia and metabolic muscle activity on staging FDG PET/CT has been shown to correlate with overall survival in certain oncologic settings. Knowledge of the physiologic FDG uptake in skeletal muscles and optimization of imaging protocols are key for proper image analysis.

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).

Detection of pulmonary artery atherosclerosis by FDG-PET/CT: a new observation.

The aim of this study was to investigate the feasibility of FDG-PET/CT imaging to detect pulmonary artery atherosclerosis and to assess the correlation between pulmonary function testing (PFT) results and the overall pulmonary artery metabolic activity. Twenty-nine subjects between the ages of 57-75, with a history of clinical suspicion of lung cancer, underwent PET/CT imaging at 3 hours following the administration of FDG. Global FDG uptake in the central pulmonary artery branches was determined. Average SUVmax, SUVmean, and tissue-to-background (TBR) mean and maximum were calculated within each vessel. The degree of FDG uptake in non-COPD and COPD patients and its correlation with PFT were examined in this population. Furthermore, the results from patients were compared with those of 10 age-matched controls. Based on these data, the number of lesions with varying degrees of FDG uptake among patients was higher than that in the normal control group. However, there was no statistically significant difference in average SUVmax, average SUVmean, average TBRmax, or average TBRmean between non-COPD and COPD patients. This indicates that the atherosclerotic process is focal and is not diffuse in nature. Although the global quantitative data generated did not reveal evidence for diffuse artery inflammation in patients with COPD, qualitative examination showed clear-cut evidence for focally increased FDG uptake in the pulmonary arteries. This observation indicates the presence of atherosclerotic plaques which are prevalent in patients with COPD. Future prospective studies with larger numbers of subjects are needed to confirm this important observation.

Assessing the effects of body weight on subchondral bone formation with quantitative 18F-sodium fluoride PET.

OBJECTIVES: The aim of this study was to quantify subchondral bone remodeling in the elbows, hands, knees, and feet using volumetric and metabolic parameters derived from 18F-sodium fluoride positron emission tomography (NaF-PET) and to assess the convergent validity of these parameters as an index of joint degeneration and preclinical osteoarthritis. METHODS: A retrospective analysis was conducted in 34 subjects (32 males, 2 females) with metastatic bone disease who underwent full-body NaF-PET/CT scans. An adaptive contrast-oriented thresholding algorithm was applied to segment NaF-avid regions in the bilateral elbows, hands, knees, and feet of each subject, and metabolically active volume (MAV), maximum standardized uptake value (SUVmax), mean metabolic volumetric product (MVPmean), and partial volume-corrected MVPmean (cMVPmean) of the segmented regions were calculated. Global parameters for MAV, SUVmax, MVPmean, and cMVPmean were defined as the sum of the corresponding values in all the joints of a subject. Inter-rater reliability was determined with Lin's concordance correlation, and associations of global values with subject body weight and age were assessed with Pearson correlation and Spearman correlation analyses. RESULTS: Inter-rater reliability was observed to be the highest in SUVmax (ρc = 0.99), followed by MVPmean (ρc = 0.96), cMVPmean (ρc = 0.93), and MAV (ρc = 0.93). MAV, MVPmean, and cMVPmean were observed to significantly increase with weight (all p < 0.0001) determined by Pearson correlation. In addition, Spearman rank-order analysis demonstrated a significant correlation between SUVmax and weight in addition to MAV, MVPmean, and cMVPmean and weight (all p < 0.01). No significant association between age and any PET parameter was observed. CONCLUSIONS: These preliminary data demonstrate the feasibility and reliability of assessing bone turnover at the joints using quantitative NaF-PET. Our findings corroborate the fact that biomechanical factors including mechanical loading and weight-bearing are contributors to osteoarthritis disease progression.

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.

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.

Role of FDG-PET/CT in Assessing the Correlation Between Blood Pressure and Myocardial Metabolic Uptake.

OBJECTIVES: We aimed to assess the association between blood pressure and LV myocardial uptake of FDG, hypothesizing that subjects with raised blood pressure would have higher FDG uptake. METHODS: We analyzed 86 healthy controls who underwent PET/CT imaging 180 minutes following FDG (4 MBq/Kg) administration. LV myocardial analysis was performed on axial sections using standard operator guided computer software (OsiriX MD). The average LV myocardial SUVmean (MSUVmean) was calculated for each subject. Subjects were assessed according to the 2017 ACC/AHA guidelines for high blood pressure in adults. Mean arterial blood pressure (MABP) was calculated for each patient. Regression models were employed for statistical analysis. RESULTS: The association of MSUVmean was more pronounced with DP (r=0.32, p=0.003) than SP (r=0.28, p=0.010); MABP was comparable (r=0.33, p=0.002). Correlations of MSUVmean with categorized BPs were: normal SP (r=0.27, p=0.010), elevated SP (r=0.28, p=0.009), stage 1 SP (r=0.27, p=0.010), stage 2 SP (r=0.28, p=0.008); normal DP (r=0.33, p=0.001), stage 1 DP (r=0.34, p=0.001), stage 2 DP (r=0.35, p=0.001). Multivariate analysis demonstrated DP (p=0.006), MABP (p=0.007), and SP (0.026). CONCLUSION: LV myocardial FDG uptake was higher in subjects with elevated blood pressure and correlated positively with SBP and in particular DBP and MABP.

18F-FDG-PET/CT in measuring volume and global metabolic activity of thigh muscles: a novel CT-based tissue segmentation methodology.

PURPOSE: We present a novel computed tomography-based tissue segmentation methodology for determining volume and global uptake of FDG of the thigh muscles and correlate these parameters with age. MATERIALS AND METHODS: A total of 71 subjects from a prospective clinical trial (NCT01724749) were included. PET/CT scans were acquired 180 minutes after intravenous injection of FDG. A 3D growing region algorithm with neighborhood Hounsfield unit threshold between one and 150 was used to highlight the muscle. FDG uptake was expressed as the average mean standardized uptake value normalized for lean body mass (average SULmean). Femur volume was used to normalize thigh muscle volume to calculate normalized volume and correlate with age. RESULTS: We found a significant negative correlation between normalized volume and age (left side r = -0.262, P = 0.02; right side r = -0.286, P = 0.01). No statistically significant difference was found between SUL and age or between SUL and BMI. There was no statistically significant difference in muscle volume on the two sides. Statistically significant difference was noted in the global metabolic activity (SUL) between the two sides (left 0.39 ± 0.06, right 0.42 ± 0.08, P < 0.001), with 56/71 (78.8%) subjects having higher uptake on the right side. CONCLUSION: FDG-PET/CT using CT-based segmentation is a novel imaging modality assessing the volume and global metabolic activity of the thigh muscles. It could be possible to utilize this methodology for the research and understanding of lower limb muscle pathophysiology.

Sacroiliac Joint Asymmetry Regarding Inflammation and Bone Turnover: Assessment by FDG and NaF PET/CT.

OBJECTIVES: This study was undertaken to determine the role of computed tomography (CT)-based methodology to segment the SI joint and quantify the metabolic activity using positron emission tomography (PET). We measured tracer uptake in the right and left SI joints independently to look for differences between the two sides. Further, we correlated tracer uptake with BMI and studied the inter-observer variation with regard to estimated tracer uptake in the SI joints. METHODS: In this retrospective study, a total of 103 subjects (48 females, 55 males) from the CAMONA study database collected 2012-2016 at Odense University Hospital in Denmark were included. Mean age was 48±14.59 years, mean BMI was 26.68±4.31 kg/m2. The SI joints were segmented on fused PET/CT images using a 3D growing algorithm with adjustable upper and lower Hounsfield Units (HU) thresholds. The metabolic activities on the two sides were correlated with BMI. RESULTS: For FDG, we found a higher average SUVmean on the right side (right: 1.3±0.33, left: 1.13±0.30; <0.0001). Similarly, for NaF, the uptake was higher on the right side (right: 5.9±1.29, left: 4.27±1.23; <0.0001). Positive correlations were present between BMI and FDG uptake (P<0.01) as well as NaF uptake (P<0.01). CONCLUSION: The PET-based molecular imaging probes along with the CT-based segmentation techniques revealed a significant difference in the metabolic activity between the two SI joints with higher inflammation and reactive bone formation on the right side. FDG and NaF uptakes correlated significantly and positively with BMI.

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.

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.

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.

Clinical Applications of Positron Emission Tomography in the Evaluation of Spine and Joint Disorders.

Over the last decade, major advances have been made in PET imaging, including the introduction of hybrid PET/computed tomography and PET/MR imaging systems, facilitating a better understanding of the pathophysiology underlying a vast array of human diseases. PET has not only remained the clinical standard for most oncological disorders but also emerged as a potentially viable modality in nononcological disorders, including many musculoskeletal pathologies.

Evolving Role of PET/CT-MRI in Assessing Muscle Disorders.

2-Deoxy-2-[18F]fluoroglucose (FDG) uptake in muscle is influenced by many normal physiologic processes and can also indicate pathology. Variability in physiologic uptake can be reduced with proper patient preparation, allowing for a better determination of abnormal activity. Although malignant diseases, such as rhabdomyosarcoma and skeletal muscle metastasis, are clear applications of FDG-PET/CT, there may be additional applications in infection and benign inflammatory disorders that warrant further research.

Incidental 18F-NaF Uptake in Drug-Induced Gynecomastia.

Gynecomastia is not uncommon in men older than 50 years of age and is characterized by glandular proliferation of breast tissue. Non-physiologic gynecomastia is mostly caused by a variety of external medical interventions. Medications that belong to classes of antiandrogens, antipsychotics, or antibiotics alter the levels of estrogen and testosterone and are commonly implicated in patients with gynecomastia. We are presenting a case of bilateral F-NaF uptake in the breast tissue of a 56-year-old man with known history of prostate cancer.

Efficacy of 18F-FDG and 18F-NaF PET/CT imaging: A novel semi-quantitative assessment of the effects of age and obesity on hip joint inflammation and bone degeneration.

OBJECTIVE: Osteoarthritis (OA) is characterized by synovial tissue inflammation and underlying bone degeneration in the joints. Aging and obesity are among the major risk factors. This study evaluated the effects of aging and body mass index (BMI) on hip joint inflammation and bone degeneration using fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and fluorine-18 sodium fluoride (18F-NaF) PET/CT imaging, respectively. SUBJECTS AND METHODS: In this retrospective study, a total of 116 subjects (58 males and 58 females) who had undergone both 18F-FDG and 18F-NaF PET/CT imaging were analyzed. The mean age of these subjects was 48.6±14.5 with an age range of 21-75 years. Fluorine-18-FDG and 18F-NaF PET/CT imaging was conducted 180min and 90min (respectively) after intravenous administration of the appropriate tracer. The hip joint was segmented on fused PET/CT images using OsiriX MD v.9.5 (DICOM viewer and image-analysis program, Pixmeo SARL; Bernex, Switzerland). The region of interest (ROI) for the hip joint was indicated by using a 3D-growing region algorithm with upper/lower Hounsfield Units (HU) followed by a morphological closing algorithm. The metabolic activity for the left and right side of the joint was measured and correlated with age and BMI. RESULTS: Fluorine-18-FDG uptake in the hip was 0.83±0.22 (right side: 0.83±0.23, left side: 0.83±0.22, P=0.82). Fluorine-18-NaF uptake in the hip was 3.20±1.07 (right side: 3.25±1.14, left side: 3.15±1.04, P=0.02). Body mass index positively correlated with both 18F-FDG (r=0.29, P=0.001) and NaF (r=0.26, P=0.005) uptake. No significant correlation was seen between age and either 18F-FDG (r=0.12, P=0.19) or 18F-NaF (r=0.03, P=0.78) uptake. CONCLUSION: Body mass index had a significant impact on 18F-FDG and 18F-NaF uptake, whereas age had no correlation with either tracer uptake. Obesity increases the mechanical forces applied on weight-bearing joints such as the hip. Body mass index was related to increased joint inflammation and bone degeneration. These findings further support the studies explaining the role of adipose tissue in promoting OA.