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1.
18F-sodium fluoride positron emission tomography (NaF-18-PET/CT) radiomic signatures to evaluate responses to alpha-particle Radium-223 dichloride therapy in osteosarcoma metastases.
Kairemo, K, Roszik, J, Anderson, P, Ravizzini, G, Rao, A, Macapinlac, HA, Subbiah, V
Current problems in cancer. 2021;(5):100797
Abstract
Patients with osteoblastic metastases from high risk osteosarcoma continue to have a poor prognosis after progression from standard-of-care multi-agent chemotherapy. In a first-in-human dose escalation trial of bone targeted Radium 223 dichloride alpha-particle therapy in 18 patients with advanced osteosarcoma only 1 patient responded based on conventional Response Evaluation Criteria in Solid Tumors (RECIST). Na18F PET response Criteria in Solid Tumors(NAFCIST), based on Sodium fluoride-18 (Na18F) positron emission tomography (PET)-CT was developed to better evaluate bone specific response. To further appreciate the spatial and temporal heterogeneity of the partial or mixed responses, a radiomics method was developed. Analyses were performed with 18F-sodium fluoride positron emission tomography imaging studies before and after alpha-particle therapy. Radioactive 18F- -atom concentrations were measured in soft-tissues, in approximately 1000 concentration data points for 18F- per 1 cm3 metastatic tumor. Data was analyzed from the SUV intensity values, the histogram of intensities and entropy values. Radiomics may inform intra-tumoral and inter-tumoral heterogeneity in response of bone forming osteosarcoma to alpha particle therapy. Each patient (and each tumor) represents an "N of 1" case and warrants in depth analysis individually.
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2.
A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using 18F-FES PET/CT imaging.
Jager, A, de Vries, EGE, der Houven van Oordt, CWM, Neven, P, Venema, CM, Glaudemans, AWJM, Wang, Y, Bagley, RG, Conlan, MG, Aftimos, P
Breast cancer research : BCR. 2020;(1):97
Abstract
BACKGROUND Elacestrant is an oral selective estrogen receptor (ER) degrader. This phase 1b open-label, non-randomized study (RAD1901-106) was initiated to determine the effect of elacestrant on the availability of ER in lesions from postmenopausal women with ER+ advanced breast cancer (ABC) using 16α-18F-fluoro-17β-estradiol positron emission tomography with low-dose computed tomography (FES-PET/CT). METHODS Eligible patients were postmenopausal women with ER+, HER2- ABC; tumor progression after ≥ 6 months of 1-3 lines of endocrine treatment for ABC; and measurable or evaluable disease. Two 8-patient cohorts were enrolled: one treated with 400 mg elacestrant once daily (QD) and one treated with 200 mg elacestrant QD with dose escalation to 400 mg QD after 14 days. Elacestrant was dosed continuously until progressive disease, toxicity, or withdrawal. FES-PET/CT was performed pre-dose at baseline and 4 h post-dose on day 14. The primary endpoint was the percentage difference in FES uptake in tumor lesions (maximum 20) after 14 days of treatment compared to baseline. Overall response was investigator-assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1. RESULTS Patients (n = 16; median age, 53.5 years) had ABC with a median 2.5 prior lines of endocrine therapy. Median reduction in tumor FES uptake from baseline to day 14 was 89.1% (Q1, Q3: 75.1%, 94.1%) and was similar in both cohorts (89.1% [Q1, Q3: 67.4%, 94.2%], 200/400 mg and 88.7% [Q1, Q3: 79.5%, 94.1%], 400 mg). Residual ER availability (> 25% persistence in FES uptake) on day 14 was observed in 3 patients receiving 200/400 mg (3/78, 37.5%) and 1 patient receiving 400 mg (1/8, 12.5%). The overall response rate (ORR) was 11.1% (1 partial response), and clinical benefit rate (CBR) was 30.8%. Median percentage change in FES uptake did not correlate with ORR or CBR. Adverse events occurring in > 20% of the patients were nausea (68.8%), fatigue (50.0%), dyspepsia (43.8%), vomiting (37.5%), and decreased appetite, dysphagia, and hot flush (31.3% each). Most events were grade 2 in severity. CONCLUSION Elacestrant 200 mg and 400 mg QD greatly reduced ER availability measured by FES-PET/CT. In a heavily pretreated population, elacestrant was associated with antitumor activity. TRIAL REGISTRATION ClinicalTrials.gov, NCT02650817 . Registered on 08 January 2016.
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3.
Assessing the feasibility of NaF-PET/CT versus FDG-PET/CT to detect abdominal aortic calcification or inflammation in rheumatoid arthritis patients.
Seraj, SM, Raynor, WY, Revheim, ME, Al-Zaghal, A, Zadeh, MZ, Arani, LS, Rojulpote, C, Werner, TJ, Gerke, O, Høilund-Carlsen, PF, et al
Annals of nuclear medicine. 2020;(6):424-431
Abstract
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.
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4.
Prospective Comparison of PET Imaging with PSMA-Targeted 18F-DCFPyL Versus Na18F for Bone Lesion Detection in Patients with Metastatic Prostate Cancer.
Rowe, SP, Li, X, Trock, BJ, Werner, RA, Frey, S, DiGianvittorio, M, Bleiler, JK, Reyes, DK, Abdallah, R, Pienta, KJ, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2020;(2):183-188
Abstract
Bone metastases in prostate cancer (PCa) have important prognostic significance, and imaging modalities used for PCa staging should have high sensitivity for detecting such lesions. Prostate-specific membrane antigen (PSMA)-targeted PET radiotracers are promising new agents for imaging PCa. We undertook a head-to-head comparison of PSMA-targeted 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET to Na18F PET to determine which modality was more sensitive for the detection of lesions suggestive of bone metastases in a group of patients with metastatic PCa. Methods: Patients with progressive, metastatic PCa were prospectively imaged with both 18F-DCFPyL and Na18F PET/CT, with both scans occurring within 24 h of each other. A consensus 2-reader central review was performed to identify all bone lesions suggestive of sites of PCa involvement on both scans, and maximized SUVs corrected for body weight (SUVmax) and lean body mass (SULmax) were recorded. Soft-tissue lesions were also noted on both scans, and SUVmax, SULmax, and PSMA reporting and data system (RADS) version 1.0 scores were recorded. Data from the 2 scans were compared using a generalized estimating equation. Results: In total, 16 patients meeting all inclusion criteria were enrolled in this study, and 15 of the 16 (93.8%) were imaged with both PET radiotracers. In total, 405 bone lesions suggestive of sites of PCa were identified on at least 1 scan. On 18F-DCFPyL PET/CT, 391 (96.5%) were definitively positive, 4 (1.0%) were equivocally positive, and 10 (2.5%) were negative. On Na18F PET/CT, the corresponding values were 388 (95.8%), 4 (1.0%), and 13 (3.2%). Of the definitively negative lesions on 18F-DCFPyL PET, 8 of 10 (80.0%) were sclerotic and 2 of 10 (20.0%) were infiltrative or marrow-based. Additionally, 12 of 13 (92.3%) of the definitively negative lesions on Na18F PET were infiltrative or marrow-based and 1 of 13 (7.7%) was lytic. Also identified were 78 PSMA-RADS-4, 17 PSMA-RADS-5, and 1 PSMA-RADS-3C soft-tissue lesions. Conclusion: PET/CT imaging using 18F-DCFPyL and Na18F PET had nearly identical sensitivities for the detection of bone lesions in patients with metastatic PCa. As would be expected, PSMA-targeted PET provides more information on soft-tissue disease. There may be little additional value to imaging PCa patients with Na18F after a PSMA-targeted PET scan has already been performed.
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5.
Head-to-Head Comparison of 18F-Prostate-Specific Membrane Antigen-1007 and 18F-Fluorocholine PET/CT in Biochemically Relapsed Prostate Cancer.
Witkowska-Patena, E, Giżewska, A, Dziuk, M, Miśko, J, Budzyńska, A, Walęcka-Mazur, A
Clinical nuclear medicine. 2019;(12):e629-e633
Abstract
PURPOSE OF THE REPORT The aim of the study was to prospectively compare performance of F-fluorocholine (FCH) and F-prostate-specific membrane antigen (PSMA)-1007 PET/CT in patients with biochemical relapse (BCR) of prostate cancer and low prostate-specific antigen levels. METHODS We prospectively enrolled 40 BCR patients after radical treatment and prostate-specific antigen levels 2.0 ng/mL or less. F-FCH and F-PSMA-1007 PET/CT imaging was performed within a mean interval of 54 ± 21 days. Scans were done 87 ± 10 and 95 ± 12 minutes after injecting 248 ± 35 and 295 ± 14 MBq of F-FCH and F-PSMA-1007, respectively. Rates of negative, equivocal, and positive scan results were compared per patient. Per lesion, findings were grouped as equivocal or highly suggestive of malignancy and then compared for their number, localization (local relapse, lymph nodes, bones), and SUVmax values. RESULTS Positive, equivocal, and negative results were reported in 60%, 27.5%, and 12.5% of F-PSMA-1007 and in 5%, 37.5%, and 57.5% of F-FCH scans, respectively. In 70% of scans, F-PSMA-1007 PET/CT upgraded F-FCH PET/CT results. F-PSMA-1007 scans also showed significantly more lesions (184 vs 63, P = 0.0006). Local relapse, lymph node, and bone lesions accounted, respectively, for 9%, 58%, and 33% of F-PSMA-1007 and 5%, 89%, and 6% F-FCH of PET/CT findings. Highly suspicious lesions accounted for 74% of F-PSMA-1007 and 11% of F-FCH PET/CT findings. In F-PSMA-1007 PET/CT SUVmax values of highly suggestive lesions were significantly higher than in equivocal lesions (median, 3.6 vs 2.5; P < 0.00001). CONCLUSIONS In early BCR patients F-PSMA-1007 showed a higher detection rate than F-FCH PET/CT. The former also showed more lesions in total, more highly suggestive lesions and less equivocal lesions.
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6.
The Clinical Impact of Using 18F-FDG-PET/CT in the Diagnosis of Suspected Vasculitis: The Effect of Dose and Timing of Glucocorticoid Treatment.
Taimen, K, Salomäki, SP, Hohenthal, U, Mali, M, Kajander, S, Seppänen, M, Nuutila, P, Palomäki, A, Roivainen, A, Pirilä, L, et al
Contrast media & molecular imaging. 2019;:9157637
Abstract
18F-Fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) with computed tomography (CT) is effective for diagnosing large vessel vasculitis, but its usefulness in accurately diagnosing suspected, unselected vasculitis remains unknown. We evaluated the feasibility of 18F-FDG-PET/CT in real-life cohort of patients with suspicion of vasculitis. The effect of the dose and the timing of glucocorticoid (GC) medication on imaging findings were in special interest. 82 patients with suspected vasculitis were evaluated by whole-body 18F-FDG-PET/CT. GC treatment as prednisolone equivalent doses at the scanning moment and before imaging was evaluated. 38/82 patients were diagnosed with vasculitis. Twenty-one out of 38 patients had increased 18F-FDG accumulation in blood vessel walls indicating vasculitis in various sized vessels. Vasculitis patients with a positive vasculitis finding in 18F-FDG-PET/CT had a significantly shorter duration of GC use (median = 4.0 vs 7.0 days, P=0.034), and they used lower GC dose during the PET scan (median dose = 15.0 mg/day vs 40.0 mg/day, p=0.004) compared to 18F-FDG-PET/CT-negative patients. Vasculitis patients with a positive 18F-FDG-PET/CT result had significantly higher C-reactive protein (CRP) than patients with a negative 18F-FDG-PET/CT finding (mean value = 154.5 vs 90.4 mg/L, p=0.018). We found that 18F-FDG-PET/CT positivity was significantly associated with a lower dose and shorter duration of GC medication and higher CRP level in vasculitis patients. 18F-FDG-PET/CT revealed clinically significant information in over half of the patients and was effective in confirming the final diagnosis.
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7.
Imaging disease activity of rheumatoid arthritis by macrophage targeting using second generation translocator protein positron emission tomography tracers.
Bruijnen, STG, Verweij, NJF, Gent, YYJ, Huisman, MC, Windhorst, AD, Kassiou, M, van de Ven, PM, Lammertsma, AA, Hoekstra, OS, Voskuyl, AE, et al
PloS one. 2019;(9):e0222844
Abstract
BACKGROUND Positron emission tomography (PET) imaging of macrophages using the translocator protein (TSPO) tracer (R)-[11C]PK11195 has shown the promise to image rheumatoid arthritis (RA). To further improve TSPO PET for RA imaging, second generation TSPO tracers [11C]DPA-713 and [18F]DPA-714 have recently been evaluated pre-clinically showing better imaging characteristics. OBJECTIVE A clinical proof of concept study to evaluate [11C]DPA-713 and [18F]DPA-714 to visualize arthritis in RA patients. METHODS RA patients (n = 13) with at least two active hand joints were included. PET/CT scans of the hands were obtained after injection of [18F]DPA-714, [11C]DPA-713 and/or (R)-[11C]PK11195 (max. 2 tracers pp). Standardized uptake values (SUVs) and target-to-background (T/B) ratios were determined. Imaging data of the 3 different tracers were compared by pooled post-hoc testing, and by a head to head comparison. RESULTS Clinically active arthritis was present in 110 hand joints (2-17 pp). Arthritic joints were visualized with both [11C]DPA-713 and [18F]DPA-714. Visual tracer uptake corresponded with clinical signs of arthritis in 80% of the joints. Mean absolute uptake in PET-positive joints was significantly higher for [11C]DPA-713 than for [18F]DPA-714, the latter being not significantly different from (R)-[11C]PK11195 uptake. Background uptake was lower for both DPA tracers compared with that of (R)-[11C]PK11195. Higher absolute uptake and lower background resulted in two-fold higher T/B ratios for [11C]DPA-713. CONCLUSIONS [11C]DPA-713 and [18F]DPA-714 visualize arthritic joints in active RA patients and most optimal arthritis imaging results were obtained for [11C]DPA-713. Second generation TSPO macrophage PET provides new opportunities for both early diagnosis and therapy monitoring of RA.
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8.
How common is isolated cardiac sarcoidosis? Extra-cardiac and cardiac findings on clinical examination and whole-body 18F-fluorodeoxyglucose positron emission tomography.
Juneau, D, Nery, P, Russo, J, de Kemp, RA, Leung, E, Beanlands, RSB, Birnie, DH
International journal of cardiology. 2018;:189-193
Abstract
BACKGROUND Sarcoidosis is a systemic inflammatory disease which can involve nearly any organ. Clinically manifest cardiac involvement occurs in perhaps 5% of patients with sarcoidosis. The reported prevalence of isolated cardiac sarcoidosis (CS) varies widely with reported rates of 27-54%. The explanation for this variability is likely multi-factorial but perhaps mostly related to the diagnostic method(s) for assessing extra-cardiac involvement. The primary aim of this study was to assess the rate of isolated CS in a homogeneous, prospectively recruited cohort of patients with clinically manifest CS, using whole body FDG PET-CT imaging as a gold standard. A secondary aim was to describe the extent and distribution of extra-cardiac sarcoidosis at the time of first presentation of clinically manifest CS. METHODS Patients were prospectively recruited at the time of first presentation with cardiac symptoms. All patients underwent whole-body and cardiac 18F-FDG PET-CT. All patients were examined for presence of skin sarcoidosis and were assessed by an ophthalmologist. RESULTS 31 patients were included (mean age 56±8years, 17 female, 100% Caucasian). Patients had limited extra-cardiac involvement (mean of 2.2 organs) however using the most precise definition, only 1/31 (3.2%) patients had isolated CS. There were marked differences in right ventricular (RV) and atrial involvement between patients presenting with CS as first presentation compared to patients presenting initially with extra-cardiac disease. CONCLUSIONS Most patients had limited extra-cardiac involvement at the time of presentation of manifest CS however, isolated CS, using the proposed gold standard, was only observed in one patient.
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9.
A Prospective Comparison of 18F-Sodium Fluoride PET/CT and PSMA-Targeted 18F-DCFBC PET/CT in Metastatic Prostate Cancer.
Harmon, SA, Bergvall, E, Mena, E, Shih, JH, Adler, S, McKinney, Y, Mehralivand, S, Citrin, DE, Couvillon, A, Madan, RA, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;(11):1665-1671
Abstract
The purpose of this study was to compare the diagnostic performance of 18F-DCFBC PET/CT, a first-generation 18F-labeled prostate-specific membrane antigen (PSMA)-targeted agent, and 18F-NaF PET/CT, a sensitive marker of osteoblastic activity, in a prospective cohort of patients with metastatic prostate cancer. Methods: Twenty-eight prostate cancer patients with metastatic disease on conventional imaging prospectively received up to 4 PET/CT scans. All patients completed baseline 18F-DCFBC PET/CT and 18F-NaF PET/CT scans, and 23 patients completed follow-up imaging, with a median follow-up interval of 5.7 mo (range, 4.2-12.6 mo). Lesion detection was compared across the 2 PET/CT agents at each time point. Detection and SUV characteristics of each PET/CT agent were compared with serum prostate-specific antigen (PSA) levels and treatment status at the time of baseline imaging using nonparametric statistical testing (Spearman correlation, Wilcoxon rank). Results: Twenty-six patients had metastatic disease detected on 18F-NaF or 18F-DCFBC at baseline, and 2 patients were negative on both scans. Three patients demonstrated soft tissue-only disease. Of 241 lesions detected at baseline, 56 were soft-tissue lesions identified by 18F-DCFBC only and 185 bone lesions detected on 18F-NaF or 18F-DCFBC. 18F-NaF detected significantly more bone lesions than 18F-DCFBC (P < 0.001). Correlation of PSA with patient-level SUV metrics was strong in 18F-DCFBC (ρ > 0.5, P < 0.01) and poor in 18F-NaF (ρ < 0.3, P > 0.1). When PSA levels were combined with treatment status, patients with below-median levels of PSA (<2 ng/mL) on androgen deprivation therapy (n = 11) demonstrated more lesions on 18F-NaF than 18F-DCFBC (P = 0.02). In PSA greater than 2 ng/mL, patients on androgen deprivation therapy (n = 8) showed equal to or more lesions on 18F-DCFBC than on 18F-NaF. Conclusion: The utility of PSMA-targeting imaging in metastatic prostate cancer appears to depend on patient disease course and treatment status. Compared with 18F-NaF PET/CT, 18F-DCFBC PET/CT detected significantly fewer bone lesions in the setting of early or metastatic castrate-sensitive disease on treatment. However, in advanced metastatic castrate-resistant prostate cancer, 18F-DCFBC PET/CT shows good concordance with NaF PET/CT.
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10.
Prospective comparative study of 18F-sodium fluoride PET/CT and planar bone scintigraphy for treatment response assessment of bone metastases in patients with prostate cancer.
Fonager, RF, Zacho, HD, Langkilde, NC, Fledelius, J, Ejlersen, JA, Hendel, HW, Haarmark, C, Moe, M, Mortensen, JC, Jochumsen, MR, et al
Acta oncologica (Stockholm, Sweden). 2018;(8):1063-1069
Abstract
AIM: To compare 18F-sodium fluoride positron emission tomography/computed tomography (NaF PET/CT) and 99mTc-labelled diphosphonate bone scan (BS) for the monitoring of bone metastases in patients with prostate cancer undergoing anti-cancer treatment. MATERIAL AND METHODS Data from 64 patients with prostate cancer were included. The patients received androgen-deprivation therapy (ADT), next-generation hormonal therapy (NGH) or chemotherapy. The patients had a baseline scan and 1-3 subsequent scans during six months of treatment. Images were evaluated by experienced nuclear medicine physicians and classified for progressive disease (PD) or non-PD according to the Prostate Cancer Working Group 2 (PCWG-2) criteria. The patients were also classified as having PD/non-PD according to the clinical and prostate-specific antigen (PSA) responses. RESULTS There was no difference between NaF PET/CT and BS in the detection of PD and non-PD during treatment (McNemar's test, p = .18). The agreement between BS and NaF PET/CT for PD/non-PD was moderate (Cohen's kappa 0.53, 95% confidence interval 0.26-0.79). Crude agreement between BS and NaF PET/CT for the assessment of PD/non-PD was 86% (89% for ADT, n = 28; 88% for NGH, n = 16, and 80% for chemotherapy, n = 20). In most discordant cases, BS found PD when NaF PET/CT did not, or BS detected PD on an earlier scan than NaF PET/CT. Biochemical progression (27%) occurred more frequently than progression on functional imaging (BS, 22% and NaF PET/CT, 14%). Clinical progression was rare (11%), and almost exclusively seen in patients receiving chemotherapy. CONCLUSION There was no difference between NaF PET/CT and BS in the detection of PD and non-PD; however, BS seemingly detects PD by the PCWG-2 criteria earlier than NaF-PET, which might be explained by the fact that NaF-PET is more sensitive at the baseline scan.