Dataset Information

Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer.

ABSTRACT: PET/computed tomography (CT) imaging with the sodium-(F)-fluoride/2-(F)-fluoro-2-deoxy-D-glucose (F-NaF/F-FDG) cocktail has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castration-resistant prostate cancer (mCRPC).The study was carried out on six patients with mCRPC, with a total of 26 analyzed lesions. The patients were injected with F-NaF and F-FDG at separate time points. Dynamic PET/CT imaging recorded the uptake time course for both the tracers into osseous metastases. F-NaF and F-FDG uptakes were decoupled by kinetic analysis, which enabled calculation of F-NaF and F-FDG standardized uptake values (SUVs) images. Peak, mean, and total SUVs were evaluated for both tracers and all visible lesions. The F-NaF/F-FDG cocktail was optimized under the assumption that the contribution of both tracers to image formation is equal. SUV images from PET/CT imaging with a combination of F-NaF and F-FDG were generated for cocktail compositions with an F-NaF?:?F-FDG ratio varying from 1?:?8 to 1?:?2.The F-NaF peak and mean SUVs were on average four to five times higher than the F-FDG peak and mean SUVs, with an interlesion coefficient of variations of 20%. The total SUV for F-NaF was on average seven times higher than that for F-FDG. When the F-NaF?:?F-FDG ratio changed from 1?:?8 to 1?:?2, the typical SUV on the generated PET images increased by 50%, whereas the change in the uptake visual pattern was hardly noticeable.F-NaF and F-FDG in the cocktail contribute equally to image formation when the F-NaF?:?F-FDG ratio is 1?:?5. Therefore, we propose this ratio as the optimal cocktail composition for mCRPC patients. We also urge to strictly control the cocktail composition during any F-NaF/F-FDG cocktail PET/CT examination.

SUBMITTER: Simoncic U

PROVIDER: S-EPMC4626289 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer.

Simoncic Urban U Perlman Scott S Liu Glenn G Jeraj Robert R

Nuclear medicine communications 20151201 12

<h4>Background</h4>PET/computed tomography (CT) imaging with the sodium-(F)-fluoride/2-(F)-fluoro-2-deoxy-D-glucose (F-NaF/F-FDG) cocktail has been proposed for patients with osseous metastases. This work aimed to optimize the cocktail composition for patients with metastatic castration-resistant prostate cancer (mCRPC).<h4>Materials and methods</h4>The study was carried out on six patients with mCRPC, with a total of 26 analyzed lesions. The patients were injected with F-NaF and F-FDG at separa ...[more]

PMID: 26378490

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Project description:: Radium-223 dichloride (Ra223) represents the unique bone-directed treatment option that shows an improvement in overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). However, there is an urgent need for the identification of reliable biomarkers to non-invasively determine its efficacy (possibly improving patients' selection or identifying responders' after therapy completion). 18F-Fluorodeoxyglucose (FDG)-avidity is low in naïve prostate cancer, but it is enhanced in advanced and chemotherapy-refractory mCRPC, providing prognostic insights. Moreover, this tool showed high potential for the evaluation of response in cancer patients with bone involvement. For these reasons, FDG Positron Emission Tomography (FDG-PET) might represent an effective tool that is able to provide prognostic stratification (improving patients selection) at baseline and assessing the treatment response to Ra223. We conducted a retrospective analysis of 28 mCRPC patients that were treated with Ra223 and submitted to bone scan and FDG-PET/CT for prognostic purposes at baseline and within two months after therapy completion. The following parameters were measured: number of bone lesions at bone scan, SUVmax of the hottest bone lesion, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). In patients who underwent post-therapy 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), (20/28), PET Response Criteria in Solid Tumors (PERCIST), and European Organization for Research and Treatment of Cancer (EORTC) criteria were applied to evaluate the metabolic treatment response. The difference between end of therapy and baseline values was also calculated for Metabolic Tumor Volume (MTV), TLG, prostate-specific antigen (PSA), alkaline phosphatase (AP), and lactate dehydrogenase (LDH) (termed deltaMTV, deltaTLG, deltaPSA, deltaAP and deltaLDH, respectively). Predictive power of baseline and post-therapy PET- and biochemical-derived parameters on OS were assessed by Kaplan-Meier, univariate and multivariate analyses. At baseline, PSA, LDH, and MTV significantly predicted OS. However, MTV (but not PSA nor LDH) was able to identify a subgroup of patients with worse prognosis, even after adjusting for the number of lesions at bone scan (which, in turn, was not an independent predictor of OS). After therapy, PERCIST criteria were able to capture the response to Ra223 by demonstrating longer OS in patients with partial metabolic response. Moreover, the biochemical parameters were outperformed by PERCIST in the post-treatment setting, as their variation after therapy was not informative on long term OS. The present study supports the role of FDG-PET as a tool for patient's selection and response assessment in mCRPC patients undergoing Ra223 administration.

Project description:The aim of this prospective investigation was to assess the association of parameters derived from baseline (18)F-FDG PET/CT with overall survival (OS) in men with castrate-resistant metastatic prostate cancer.Eighty-seven men with castrate-resistant metastatic prostate cancer underwent (18)F-FDG PET/CT and were followed prospectively for OS. Median follow-up in patients who were alive was 22.2 mo (range, 1.6-62.5 mo). OS was defined as the time between the PET/CT imaging or the start of chemotherapy, whichever was later, and death, with patients who were alive censored at the last follow-up date. PET parameters included maximum standardized uptake value (SUV(max)) of the most active lesion, sum of SUV(max), and average SUV(max) of all metabolically active lesions, after subtraction of patient-specific background-liver average SUV. Comparison of OS was based on univariate and multivariable Cox regression analyses of continuous PET parameters adjusted for standard clinical parameters (age, serum prostate-specific antigen level, alkaline phosphatase, use of pain medication, prior chemotherapy, and Gleason score at initial diagnosis). Survival curves based on Kaplan-Meier estimates are presented.Among the 87 patients, 61 were dead at the time of last follow-up. Median OS was 16.5 mo (95% confidence interval [CI], 12.1-23.4 mo), and the OS probability at 24 mo was 39% ± 6%. For the univariate analysis, the hazard ratios associated with each unit increase were 1.01 (95% CI, 1.006-1.02) for sum of SUV(max) (P = 0.002), 1.11 (95% CI, 1.03-1.18) for maximum SUV(max) (P = 0.010), and 1.13 (95% CI, 0.99-1.30) for average SUV(max) (P = 0.095). For the multivariable analysis adjusting for relevant clinical parameters, the continuous parameter sum of SUV(max) remained significant (P = 0.053), with a hazard ratio of 1.01 (95% CI, 1.001-1.02). When sum of SUV(max) was grouped into quartile ranges, there was poorer survival probability for the patients in the fourth-quartile range than for those in the first-quartile range, with a univariate hazard ratio of 3.8 (95% CI, 1.8-7.9).Sum of SUV(max) derived from (18)F-FDG PET/CT contributes independent prognostic information on OS in men with castrate-resistant metastatic prostate cancer, and this information may be useful in assessing the comparative effectiveness of various conventional and emerging treatment strategies.

Project description:Assessing therapy response of breast cancer bone metastases is challenging. In retrospective studies, serial 18F-FDG PET was predictive of time to skeletal related events (tSRE) and time-to-progression (TTP). 18F-NaF PET improves bone metastasis detection compared to bone scans. We prospectively tested 18F-FDG PET and 18F-NaF PET to predict tSRE, TTP, and overall survival (OS) in patients with bone-dominant metastatic breast cancer (BD MBC). Methods: Patients with BD MBC were imaged with 18F-FDG PET and 18F-NaF PET prior to starting new therapy (scan1) and again at a range of times centered around approximately 4 months later (scan2). SUVmax and SULpeak were recorded for a single index lesion and up to 5 most dominant lesions for each scan. tSRE, TTP, and OS were assessed exclusive of the PET images. Univariate Cox regression was performed to test the association between clinical endpoints and 18F-FDG PET and 18F-NaF PET measures. mPERCIST (Modified PET Response Criteria in Solid Tumors) criteria were also applied. Survival curves for mPERCIST compared response categories of Complete Response+Partial Response+Stable Disease versus Progressive Disease (CR+PR+SD vs PD) for tSRE, TTP, and OS. Results: Twenty-eight patients were evaluated. Higher FDG SULpeak at scan2 predicted shorter time to tSRE (P = <0.001) and TTP (P = 0.044). Higher FDG SUVmax at scan2 predicted a shorter time to tSRE (P = <0.001). A multivariable model using FDG SUVmax of the index lesion at scan1 plus the difference in SUVmax of up to 5 lesions between scans was predictive for tSRE and TTP. Among 24 patients evaluable by 18F-FDG PET mPERCIST, tSRE and TTP were longer in responders (CR, PR, or stable) compared to non-responders (PD) (P = 0.007, 0.028 respectively), with a trend toward improved survival (P = 0.1). An increase in the uptake between scans of up to 5 lesions by 18F-NaF PET was associated with longer OS (P = 0.027). Conclusion: Changes in 18F-FDG PET parameters during therapy are predictive of tSRE and TTP, but not OS. mPERCIST evaluation in bone lesions may be useful in assessing response to therapy and is worthy of evaluation in multicenter, prospective trials. Serial 18F-NaF PET was associated with OS, but was not useful for predicting TTP or tSRE in BD MBC.

Project description:UnlabelledConventional imaging modalities (CIMs) have limited sensitivity and specificity for detection of metastatic prostate cancer. We examined the potential of a first-in-class radiofluorinated small-molecule inhibitor of prostate-specific membrane antigen (PSMA), N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-(18)F-fluorobenzyl-l-cysteine ((18)F-DCFBC), to detect metastatic hormone-naïve (HNPC) and castration-resistant prostate cancer (CRPC).MethodsSeventeen patients were prospectively enrolled (9 HNPC and 8 CRPC); 16 had CIM evidence of new or progressive metastatic prostate cancer and 1 had high clinical suspicion of metastatic disease. (18)F-DCFBC PET/CT imaging was obtained with 2 successive PET scans starting at 2 h after injection. Patients were imaged with CIM at approximately the time of PET. A lesion-by-lesion analysis of PET to CIM was performed in the context of either HNPC or CRPC. The patients were followed with available clinical imaging as a reference standard to determine the true nature of identified lesions on PET and CIM.ResultsOn the lesion-by-lesion analysis, (18)F-DCFBC PET was able to detect a larger number of lesions (592 positive with 63 equivocal) than CIM (520 positive with 61 equivocal) overall, in both HNPC and CRPC patients. (18)F-DCFBC PET detection of lymph nodes, bone lesions, and visceral lesions was superior to CIM. When intrapatient clustering effects were considered, (18)F-DCFBC PET was estimated to be positive in a large proportion of lesions that would be negative or equivocal on CIM (0.45). On follow-up, the sensitivity of (18)F-DCFBC PET (0.92) was superior to CIM (0.71). (18)F-DCFBC tumor uptake was increased at the later PET time point (~2.5 h after injection), with background uptake showing a decreasing trend on later PET.ConclusionPET imaging with (18)F-DCFBC, a small-molecule PSMA-targeted radiotracer, detected more lesions than CIM and promises to diagnose and stage patients with metastatic prostate cancer more accurately than current imaging methods.

Project description:18F-NaF, a PET radiotracer of bone turnover, has shown potential as an imaging biomarker for assessing the response of bone metastases to therapy. This study aimed to evaluate the repeatability of 18F-NaF PET-derived SUV imaging metrics in individual bone lesions from patients in a multicenter study.MethodsThirty-five castration-resistant prostate cancer patients with multiple metastases underwent 2 whole-body (test-retest) 18F-NaF PET/CT scans 3 ± 2 d apart from 1 of 3 imaging sites. A total of 411 bone lesions larger than 1.5 cm3 were automatically segmented using an SUV threshold of 15 g/mL. Two levels of analysis were performed: lesion-level, in which measures were extracted from individual-lesion regions of interest (ROI), and patient-level, in which all lesions within a patient were grouped into a patient ROI for analysis. Uptake was quantified with SUVmax, SUVmean, and SUVtotal Test-retest repeatability was assessed using Bland-Altman analysis, intraclass correlation coefficient (ICC), coefficient of variation, critical percentage difference, and repeatability coefficient. The 95% limit of agreement (LOA) of the ratio between test and retest measurements was calculated.ResultsAt the lesion level, the coefficient of variation for SUVmax, SUVmean, and SUVtotal was 14.1%, 6.6%, and 25.5%, respectively. At the patient level, it was slightly smaller: 12.0%, 5.3%, and 18.5%, respectively. ICC was excellent (>0.95) for all SUV metrics. Lesion-level 95% LOA for SUVmax, SUVmean, and SUVtotal was (0.76, 1.32), (0.88, 1.14), and (0.63, 1.71), respectively. Patient-level 95% LOA was slightly narrower, at (0.79, 1.26), (0.89, 1.10), and (0.70, 1.44), respectively. We observed significant differences in the variance and sample mean of lesion-level and patient-level measurements between imaging sites.ConclusionThe repeatability of SUVmax, SUVmean, and SUVtotal for 18F-NaF PET/CT was similar between lesion- and patient-level ROIs. We found significant differences in lesion-level and patient-level distributions between sites. These results can be used to establish 18F-NaF PET-based criteria for assessing treatment response at the lesion and patient levels. 18F-NaF PET demonstrates repeatability levels useful for clinically quantifying the response of bone lesions to therapy.

Dataset Information

Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer.

Publications

Optimizing an 18F-NaF and 18F-FDG cocktail for PET assessment of metastatic castration-resistant prostate cancer.

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