Assessment of regional and total skeletal metabolism using 18F-NaF PET/CT in patients with chronic kidney disease.

OBJECTIVE: The study aims to assess regional and total bone metabolic activity in patients with chronic kidney disease using Na[18F]F PET and correlation between semi-quantitative indices and blood parameters. METHODS: Seventy-two subjects (mean age 61.8 ± 13.8 years) were included. Of these 24/72 patients had end-stage renal disease (ESRD) (GFR < 15 mL/min/1.73 m2), 38/72 had chronic kidney disease (CKD) (GFR between 60 and 15 mL/min/1.73 m2), and 10/72 were controls with normal renal function. All subjects underwent Na[18F]F PET-CT with a dose activity of 0.06 mCi/Kg. Regional and total skeletal metabolism were assessed with mean SUVs in a skeletal volume of interest (VOI), bone to soft tissue index (B/S), global SUV mean (GSUV mean) of the whole bone, and uptake in the femoral neck. RESULTS: Statistically significant differences were observed in a number of 18F-NaF metrics like femoral neck metabolism in CKD and ERSD groups in comparison to control in right (P = 0.003) and left femur (P = 0.006), bone to soft tissue index in the femur (P = 0.016) and GSUV5 (P = 0.006). There is also a significant difference in SUV mean in lumbar vertebrae (L1-L4) among CKD, ESRD, and controls. There was a moderate correlation between 18F-NaF PET scan uptake and blood parameters such as ALP and PTH. Na[18F]F uptake parameters were significantly different in low versus high bone turnover state. CONCLUSIONS: The assessment of total skeleton and regional metabolism and bone turnover in CKD patients is feasible with Na[18F]F PET. Na[18F]F can help to detect early changes in bone metabolism and assess the progression of bone disease in this complex condition. Quantification with Na[18F]F PET might provide better assessment of the bone turnover. The difference in Na[18F]F uptake in CKD compared to controls is likely related to a change in bone turnover which, however, requires further validation.

Prospective study of Na[18F]F PET/CT for cancer staging in morbidly obese patients compared with [99mTc]Tc-MDP whole-body planar, SPECT and SPECT/CT.

PURPOSE: This prospective study aims to assess the diagnostic test characteristics of Na[18F]F PET/CT for the skeletal staging of cancer in morbidly obese patients compared with 99mTc-methylene diphosphonate (MDP), whole-body planar (WBS), SPECT, and SPECT/CT acquisitions. MATERIAL AND METHODS: One hundred seventeen obese patients (BMI 46.5 ± 6.1 kg/m2 and mean age, 59.0 years; range 32-89 years) with BMI > 40 kg/m2 were prospectively enrolled and underwent [99mTc]Tc-MDP WBS, SPECT, SPECT/CT, and Na[18F]F PET/CT within two weeks for the osseous staging of a malignancy. Images were assessed qualitatively using a 3-point scale. Patient and lesion-based diagnostic test characteristics were estimated using an optimistic and pessimistic dichotomization method. RESULTS: Bone metastases were confirmed in 44 patients. Patient-based optimistic diagnostic test characteristics were (sensitivity, specificity, overall accuracy): Na[18F]F PET/CT (95.5%, 95.9%, 95.7%), [99mTc]Tc-MDP WBS (52.3%, 71.2%, 64.1%), SPECT (61.4%, 80.8%, 73.5%) and SPECT/CT (65.9%, 91.8%, 82.1%). Lesion-based optimistic diagnostic test characteristics were: Na[18F]F PET/CT (97.7%, 97.9%, 97.7%), [99mTc]Tc-MDP WBS (39%, 67%, 48.9%), SPECT (52.9%, 93.6%, 67.3%) and SPECT/CT (65.9%, 91.8%, 82.1%). There was no significant difference in the specificity of Na[18F]F and SPECT/CT. All other pairwise comparisons were significant (p<.001). ROC curve analysis showed a high overall accuracy of Na[18F]F with significantly higher AUCs for Na[18F]F PET/CT compared to [99mTc]Tc-MDP WBS, SPECT, and SPECT/CT on both patient and lesion-based analysis (p<.001). Moreover, Na[18F]F PET/CT changed patient management in 38% of patients. CONCLUSIONS: Na[18F]F PET/CT may be the preferred imaging modality for skeletal staging in morbidly obese patients. The technique provides excellent diagnostic test characteristics superior to [99mTc]Tc-MDP bone scan (including SPECT/CT), impacts patient management, has an acceptable radiation exposure profile, and is well-tolerated. Further cost-effectiveness evaluations are warranted.

Incremental Value of 18F-PSMA-1007 PET/CT in Detection of Metastatic Renal Cell Carcinoma to the Brain.

ABSTRACT: 18F-PSMA PET/CT is an emerging standard of care in staging prostate cancer, evaluating biochemical recurrence and response to therapy. Despite the nomenclature, PSMA expression is also documented at the tumor-associated neovasculature of other malignant solid tumors including renal cell carcinoma. We report a case of 44-year-old man known to have renal cell carcinoma who underwent 18F-PSMA and 18F-FDG PET/CT for restaging after radical nephrectomy. A well-defined solitary cerebellar lesion with marked PSMA expression and equivocal FDG uptake was noted. MRI brain confirmed a matching cerebellar metastatic lesion. 18F-PSMA expression in the metastatic RCC raises a prospective guide to futuristic theragnostic uses.

Primary Breast Lymphoma Mimicking Metastatic Breast Cancer on 18F-FDG PET-CT.

18F-Fluorodeoxyglucose (FDG) PET-CT is an excellent imaging modality for the evaluation of non-Hodgkin lymphoma (NHL). We report a case of a 45-year-old woman presented with a large right breast mass and suspicious right axillary lymph nodes referred for 18F-FDG PET-CT for staging. 18F-FDG PET-CT images show large hypermetabolic right breast mass infiltrating the skin, multiple hypermetabolic right axillary and subpectoral lymph nodes, along with multiple hypermetabolic bone lesions at axial and appendicular skeleton. Findings are mimicking primary breast cancer with nodal and bone metastases. Biopsy revealed diffuse large B cell lymphoma. 18F-FDG PETCT is helpful in evaluation of disease extent and response evaluation of primary breast lymphoma.

Therapy-induced bone changes in oncology imaging with 18F-sodium fluoride (NaF) PET-CT.

18F-Sodium fluoride (18F-NaF) is a PET tracer that is mostly used in the evaluation of bone metastasis in oncology cases. Recently, 18F-NaF PET/CT is gaining wide popularity owing to its higher sensitivity over the other conventional bone tracer with higher and rapid single-pass extraction, negligible plasma protein binding, rapid blood, and renal clearance. In the era of constant evolution of cancer therapy regimens, considerable bone health impact is seen in the form of avascular necrosis, insufficiency fractures, among others. A significant number of these therapy-induced changes show high bone turnover and thereby 18F-NaF accumulation, mimicking metastatic lesions. This article summarizes and illustrates the pattern and morphological features of 18F-NaF PET/CT findings in these changes in the context of clinical and therapeutic history.

Case of Adult Metastatic Medulloblastoma Demonstrated on 18F-DOPA PET/CT.

ABSTRACT: 18F-DOPA is a promising radiotracer used for both staging and restaging of primary brain tumors based on increased transport via the L-type large neutral amino acid transport system in tumor cells. Adult medulloblastoma is extremely rare. We present a case of 25-year-old man with posterior fossa medulloblastoma treated with surgery followed by chemotherapy and radiotherapy 5 years back, which later developed metastasis to left cerebral lobe treated with gamma knife followed by surgical debulking. Recent 18F-DOPA PET/CT demonstrates recurrence and disease progression on follow-up scan. 18F-DOPA PET/CT is extremely useful for characterizing brain tumors, response assessment, and prognosis.

Prostate-Specific Membrane Antigen Expression in Metastatic Angiosarcoma Detected on 18F-PMSA PET/CT: A New Potential Prognostic Marker.

ABSTRACT: 18F-PSMA is a promising tracer for both staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the endothelium of tumor-associated neovasculature of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 59-year-old man with known case of prostate cancer underwent 18F-PSMA for restaging. 18F-PSMA PET/CT shows multiple lytic bone lesions with high PSMA expression. Histopathological evaluation showed metastatic angiosarcoma. 18F-PSMA expression in the angiosarcoma can be potentially guided to radionuclide legend therapy.

18F-PSMA-1007 Uptake in Paget Disease of the Bone: An "Iron Man" Sign.

ABSTRACT: 18F-PSMA is a promising tracer for both staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the benign pathological conditions. We report a case of 81-year-old man with a known case of prostate cancer who underwent 18F-PSMA for restaging. 18F-PSMA PET/CT shows intense tracer uptake in the frontal bone appearing like an "Iron Man" sign. Corresponding noncontrast CT images, pagetoid changes with thickened cortex, mixed lytic/sclerotic mottled pattern. It is important to recognize 18F-PSMA expression in the benign nonprostatic pathologies to avoid false interpretation.

The clinical effectiveness of reconstructing 18F-sodium fluoride PET/CT bone using Bayesian penalized likelihood algorithm for evaluation of metastatic bone disease in obese patients.

OBJECTIVE: A new Bayesian penalized likelihood reconstruction algorithm for positron emission tomography (PET) (Q.Clear) is now in clinical use for fludeoxyglucose (FDG) PET/CT. However, experience with non-FDG tracers and in special patient populations is limited. This pilot study aims to compare Q.Clear to standard PET reconstructions for 18F sodium fluoride (18F-NaF) PET in obese patients. METHODS: 30 whole body 18F-NaF PET/CT scans (10 patients with BMI 30-40 Kg/m2 and 20 patients with BMI >40 Kg/m2) and a NEMA image quality phantom scans were analyzed using ordered subset expectation maximization (OSEM) and Q.Clear reconstructions methods with B400, 600, 800 and 1000. The images were assessed for overall image quality (IQ), noise level, background soft tissue, and lesion detectability, contrast recovery (CR), background variability (BV) and contrast-to-noise ratio (CNR) for both algorithms. RESULTS: CNR for clinical cases was higher for Q.Clear than OSEM (p < 0.05). Mean CNR for OSEM was (21.62 ± 8.9), and for Q.Clear B400 (31.82 ± 14.6), B600 (35.54 ± 14.9), B800 (39.81 ± 16.1), and B1000 (40.9 ± 17.8). As the ß value increased the CNR increased in all clinical cases. B600 was the preferred ß value for reconstruction in obese patients. The phantom study showed Q.Clear reconstructions gave lower CR and lower BV than OSEM. The CNR for all spheres was significantly higher for Q.Clear (independent of ß) than OSEM (p < 0.05), suggesting superiority of Q.Clear. CONCLUSION: This pilot clinical study shows that Q.Clear reconstruction algorithm improves overall IQ of 18F-NaF PET in obese patients. Our clinical and phantom measurement results demonstrate improved CNR and reduced BV when using Q.Clear. A ß value of 600 is preferred for reconstructing 18F-NaF PET/CT with Q.Clear in obese patients. ADVANCES IN KNOWLEDGE: 18F-NaF PET/CT is less susceptible to artifacts induced by body habitus. Bayesian penalized likelihood reconstruction with18F-NaF PET improves overall IQ in obese patients.

18F-PSMA-1007 PET/CT for Initial Staging of Renal Cell Carcinoma in an End-Stage Renal Disease Patient.

A 46-year-old man with end-stage renal disease and renal cell carcinoma underwent F-FDG PET/CT for initial staging followed by F-PSMA-1007 PET/CT. Unlike F-FDG, which undergoes renal clearance, F-PSMA-1007 undergoes hepatobiliary clearance and thus generates superior quality images. F-PSMA-1007 PET/CT showed intense tracer-avid left renal mass lesion (FDG nonavid); lytic bone lesions (FDG avid) and single liver lesion (FDG nonavid). This case highlights the superiority of F-PSMA-1007 over F-FDG PET/CT in identifying primary lesion as well as metastatic sites in case of renal cell carcinoma even in the presence of end-stage renal disease.

Incremental Value of Post Diuretic 68Ga-PSMA-11 PET-CT in Characterization of Indeterminate lLesions in Prostate Cancer.

OBJECTIVE: The aim of current study is to evaluate the role of diuretic assisted 68Ga-PSMA PET-CT, on image quality and clinical interpretation of indeterminate/equivocal lesions in pre-Lasix imaging of Prostate cancer. MATERIALS AND METHODS: Forty-five patients underwent baseline 68Ga-PSMA-11 scan 45-60 minutes post tracer injection followed by post Lasix study after ±15 minutes. The contrast to noise ratios (CNR), noise and SUVmax were determined for the focal uptakes in both pre and post Lasix images. All continuous variables were expressed as mean ± SD. Images were assessed by two experienced physicians in order to  evaluate lesion detectability and delineations that have an impact on clinical interpretation. RESULTS: Of total 45 patients, 12/45 (27%) showed unremarkable scan along with 33/45 (73%) showing metastases. Sixteen out of 45 (36%) of the metastatic scans showed indeterminate/equivocal lesions. In these cases, post Lasix study showed false negative findings in 7/45 (16%), better delineation of lesions 10/45 (22%), better confidence towards reporting lesions as abnormal in 5/45 (11%) with an overall 11/45 (24%) of the cases who showed increase in the number of the lesions after the Lasix study. The overall CNR was evaluated using Wilcoxon Rank test (p-value = 0.02) which suggested significant improved ratios in the post-Lasix imaging by 49.6%±24.5. There was a substantial agreement (k =0.76) between the physicians when comparing the lesion clarity and delineation in post Lasix images. The average score for physician one and two being 2.4 ±0.71 and 2.53±0.52 respectively. CONCLUSION: Post diuretic 68Ga-PSMA imaging at ± 15 minutes clears the unwanted activity in the urinary tract which in turn improves the contrast to noise ratios. Thus leading to decline in false positive findings, improved diagnostic certainty of physician and better detection of indeterminate lesions in 68Ga-PSMA imaging.

Spectrum of false positive 18F-sodium fluoride (NaF) bone PET/CT findings in Oncology imaging; A narrative pictorial review of cases from a single institution.

Fluorine-18-sodium fluoride (18F-NaF) is a positron emission tomography (PET) bone imaging agent mainly used for oncology staging but may also be used in the evaluation of benign bone and joint pathology conditions. Fluorine-18-NaF is an excellent bone-seeking agent with high bone uptake owing to favorable biodistribution with rapid single-pass extraction, limited plasma protein binding and prompt renal clearance. Fluorine-18-NaF PET/computed tomography (CT) is highly sensitive in identifying both sclerotic and lytic bone metastatic lesions. Occasionally 18F-NaF uptake in benign bone lesions can mimic malignantpathology. In these cases, the pattern of 18F-NaF uptake may elicit a specific diagnosis and correlation with clinical information and morphological information from correlative CT is essential for a correct diagnosis. In the present article, we present a series of clinical cases demonstrating examples of 18F-NaF uptake in benign lesions which can simulate malignant pathology in patients undergoing cancer staging.

18F-PSMA 1007 Uptake in a Man With Metastatic Breast Cancer.

A 72-year-old man, who is known with a case of metastatic carcinoma of the breast, was referred for F-PMSA 1007 PET/CT with clinical suspicion of synchronous prostate cancer. F-PSMA 1007 PET/CT scan detected no abnormal tracer concentrating lesion in the prostate gland; however, abnormal tracer concentration was noted in soft tissue lesions in left breast, metastatic lymph nodes, and skeletal lesions. Compared with F-FDG PET/CT, more bone lesions were detected on F-PSMA 1007 imaging. The findings of our case open the possibility of imaging metastatic breast cancer with F-PSMA 1007 in men.

18F-PSMA 1007 in Suspected Renal Cell Carcinoma.

A 60-year-old man with suspected right renal cell carcinoma underwent F-FDG PET/CT and F prostate-specific membrane antigen (PSMA) 1007 PET/CT scan. Compared with the F-FDG PET/CT scan, F-PSMA 1007 PET/CT showed intense tracer concentration in the primary tumor in the right kidney and intense tracer concentration consistently in all lung nodules. Unlike noted in previous pilot studies with Ga-PSMA, we observed that the primary renal tumor also showed intense tracer avidity with F-PSMA 1007. F-PSMA 1007 PET/CT may provide preoperative insight into possible etiology, histopathological probability of tumor type, staging information, and theranostic potentials in evaluation of suspected renal cell carcinoma.

Significance of 18F-FDG PET/CT in Characterization of Equivocal Lesions in High-Risk Testicular Carcinoma in Restaging Setting.

OBJECTIVES: The present study aims to evaluate the role of Positron emission tomography (PET) -computed tomography (CT) with 18F-fluorodeoxyglucose (18F-FDG) in the restaging of high-risk testicular cancer. METHODS: Forty-five patients (mean age of 38.1±11.3 years and range 23-81 years) with testicular carcinoma, underwent 18F-FDG PET-CT during their clinical course were prospectively selected. PET positivity was defined as a site of abnormal 18F-FDG uptake in tissue histologically proven or clinically or radiographically suspected to represent tissue involvement. The sites of disease were characterized as either nodal or extranodal. All patients were followed-up for at least 12 months with a diagnostic and/or functional imaging modality. RESULTS: Of the 45 patients 38 (84%) patient presented with seminoma and 7 (16%) were Non-seminomatous germ cell tumors. Analysis of secondary disease spectrum showed nodal involvement in 65%, osseous involvement in 23% and mixed visceral/soft tissue lesions in 12% of patients. Nineteen (42%) were negative for any metastatic disease. All negative patients remain disease free in the follow-up of one year. Out of the positive 26/45 patients, PET-CT showed progressive disease in 3/26, stable disease 1/26 and partial response in 2/26 and complete metabolic resolution in 20/26 patients. 18F-FDG PET-CT was able to characterize all patients leading to significant change of primary decision of wait and watch to go for treatment and vice versa. CONCLUSION: 18F-FDG PET-CT scan is potentially an excellent tool for characterization of equivocal lesions on CT scan in the restaging settings and follow up of high-risk testicular cancer patients.

18F-PSMA 1007 Brain PET/CT Imaging in Glioma Recurrence.

A 64-year-old man with a known case of right parietal lobe glioblastoma multiforme operated on in August 2018 was referred for F-FDG PET/CT with a clinical suspicion of recurrence. He underwent F-FDG and F-PSMA 1007 scans. Both the scans showed intense tracer uptake in right parietal lobe lesion, which concurred with MRI findings of recurrent disease and was later proven on histopathologic examination as recurrence. Our case highlights the feasibility of F-PSMA 1007 PET/CT imaging of suspected glioblastoma recurrence. Considering its similarity to PSMA-617, it may be used as a surrogate imaging tracer for potential theranostic application using alpha or beta emitters.

68Ga-PMSA Uptake in the Lung: Metastatic Versus Primary Lung Tumor.

Ga-PSMA is a promising tracer for both primary staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the neovascular endothelium of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 73-year-old man of prostate cancer with rising prostate-specific antigen levels. Ga-PSMA PET/CT was performed, which showed a focal lung lesion, with subsequent histological confirmation of adenocarcinoma of the lung. Incidental lung lesions on Ga-PSMA in prostate cancer patients should elicit a differential of primary lung malignancy, especially if clinical and morphological suspicion is high.

18F-PSMA 1007 Uptake in Brain Metastases From Breast Cancer.

A 64-year-old woman with metastatic breast cancer on follow-up had suspicious recurrent brain metastases. She underwent F-FDG PET/CT, F-PSMA 1007 brain PET/CT, and brain MRI. F-PSMA 1007 showed intense tracer localization in the suspected recurrent brain metastasis in right parietal lobe and also picked up 2 more metastatic brain lesions, which had concurrent findings of metastasis in subsequent MRI. Our case highlights the feasibility of F-PSMA 1007 PET/CT imaging of brain metastases from nonprostate cancers. It may be used as surrogate imaging tracer for potential theranostic application using alpha or beta emitters considering its similarity to PSMA-617.

Normal Variant 18F-Sodium Fluoride Uptake in the Falx Cerebri Ossification.

Falx cerebri ossification is an incidental finding. Mostly it is easy to diagnose, but can be challenging in few cases, and should be distinguished from calcified meningioma, hematoma, and meningeal infiltration. We report a case of a 46-year-old woman with breast cancer complaining of back pain. F-NaF PET/CT images show focal increase uptake at facet joints of L5/S1 vertebrae and both knees joints, suggesting degenerative disease. There is normal variant F-NaF uptake noted in the ossification at the falx cerebri. Recognition of normal and abnormal extraosseous F-NaF uptake is important for correct interpretation to avoid unnecessary further investigations.

Immune Checkpoint Inhibitors (Nivolumab)-Induced Enterocolitis Demonstrated on 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography.

Nivolumab, an immune checkpoint inhibitor, is a humanized anti-programmed death-1 monoclonal antibody that is used for the treatment of various cancers after second-line chemotherapy. We report a 23-year-old male with relapsed Hodgkin's lymphoma Stage IV treated with nivolumab. After 3 months of treatment, he developed watery diarrhea and cramping abdominal pain. Follow-up positron emission tomography-computed tomography scan showed complete metabolic resolution of the disease; however, there is bowel wall thickening and colonic distension with corresponding increased fluorodeoxyglucose uptake. These findings are related to immune-related adverse event associated with nivolumab treatment, i.e., secondary enterocolitis. These adverse events can be successfully treated if timely and appropriately diagnosed.