Exploratory study of 18F-fluciclovine pet/ct for response assessment to docetaxel in patients with metastatic castration-resistant prostate cancer.
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ABSTRACT:
SUBMITTER: Akintayo AA
PROVIDER: S-EPMC8255212 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBone flare has been observed on 99mTc-MDP bone scans of patients with metastatic castration-resistant prostate cancer (mCRPC). This exploratory study investigates bone flare in mCRPC patients receiving androgen receptor (AR) inhibitors using 18F-NaF PET/CT.MethodsTwenty-nine mCRPC patients undergoing AR-inhibiting therapy (abiraterone, orteronel, enzalutamide) received NaF PET/CT scans at baseline, week 6, and week 12 of treatment. SUV metrics were extracted globally for each patient (SUV) and for each individual lesion (iSUV). Bone flare was defined as increasing SUV metrics or lesion number at week 6 followed by subsequent week 12 decrease. Differences in metrics across timepoints were compared using Wilcoxon tests. Cox proportional hazard regression was conducted between global metrics and progression-free survival (PFS).ResultsTotal SUV was most sensitive for flare detection and was identified in 14/23 (61%) patients receiving CYP17A1-inhibitors (abiraterone, orteronel), and not identified in any of six patients receiving enzalutamide. The appearance of new lesions did not account for initial increases in SUV metrics. iSUV metrics followed patient-level trends: bone flare positive patients showed a median of 72% (range: 0-100%) of lesions with total iSUV flare. Increasing mean SUV at week 6 correlated with extended PFS (HR = 0.58, p = 0.02).ConclusionNaF PET bone flare was present on 61% of mCRPC patients in the first 6 weeks of treatment with CYP17A1-inhibitors. Characterization provided in this study suggests favorable PFS in patients showing bone flare. This characterization of NaF flare is important for guiding treatment assessment schedules to better distinguish between patients showing bone flare and those truly progressing, and should be performed for all emerging mCRPC treatments and imaging agents.
| S-EPMC7490782 | biostudies-literature
Project description:Anti-1-amino-3-18fluorine-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) positron emission tomography (PET) shows preferential glioma uptake but there is little data on how uptake correlates with post-contrast T1-weighted (Gd-T1) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) activity during adjuvant treatment. This pilot study aimed to compare 18F-fluciclovine PET, DCE-MRI and Gd-T1 in patients undergoing chemoradiotherapy for glioblastoma (GBM), and in a parallel pre-clinical GBM model, to investigate correlation between 18F-fluciclovine uptake, MRI findings, and tumour biology. 18F-fluciclovine-PET-computed tomography (PET-CT) and MRI including DCE-MRI were acquired before, during and after adjuvant chemoradiotherapy (60 Gy in 30 fractions with temozolomide) in GBM patients. MRI volumes were manually contoured; PET volumes were defined using semi-automatic thresholding. The similarity of the PET and DCE-MRI volumes outside the Gd-T1 volume boundary was measured using the Dice similarity coefficient (DSC). CT-2A tumour-bearing mice underwent MRI and 18F-fluciclovine PET-CT. Post-mortem mice brains underwent immunohistochemistry staining for ASCT2 (amino acid transporter), nestin (stemness) and Ki-67 (proliferation) to assess for biologically active tumour. 6 patients were recruited (GBM 1-6) and grouped according to overall survival (OS)-short survival (GBM-SS, median OS 249 days) and long survival (GBM-LS, median 903 days). For GBM-SS, PET tumour volumes were greater than DCE-MRI, in turn greater than Gd-T1. For GBM-LS, Gd-T1 and DCE-MRI were greater than PET. Tumour-specific 18F-fluciclovine uptake on pre-clinical PET-CT corresponded to immunostaining for Ki-67, nestin and ASCT2. Results suggest volumes of 18F-fluciclovine-PET activity beyond that depicted by DCE-MRI and Gd-T1 are associated with poorer prognosis in patients undergoing chemoradiotherapy for GBM. The pre-clinical model confirmed 18F-fluciclovine uptake reflected biologically active tumour.
| S-EPMC9315674 | biostudies-literature
Project description:The aim of this prospective investigation was to assess the association of 18F-FDG PET/CT with time to hormonal treatment failure (THTF) in men with metastatic castration-sensitive prostate cancer. Methods: 76 men with metastatic castration-sensitive prostate cancer recruited from 2005 to 2011 underwent 18F-FDG PET/CT and were followed prospectively for THTF, defined as treatment change to chemotherapy or death. Patients who had not switched to chemotherapy were censored at the last follow-up date (median of 36 mo; range, 12-108 mo). Cox regression analyses were performed to examine the association between PET/CT measurements: sum of SUVmax, maximum SUVmax, and average SUVmax for up to 10 of the most active lesions and THTF. Survival probabilities were based on the Kaplan-Meier method. Results: 43 patients had hormonal treatment failure, and 8 died without documented treatment failure. Median THTF was 26.5 mo (95% confidence interval [CI], 15.5-46.6 mo). The THTF-free probability at 5 y was 35% ± 6%. On univariate analysis, all PET parameters, including number of lesions, were statistically significant for THTF. In a reduced multivariate model accounting for clinical variables, only sum of SUVmax (hazard ratio, 1.01; 95% CI, 1.002-1.03; P = 0.024) and number of lesions (hazard ratio, 1.18; 95% CI, 1.08-1.29; P < 0.001) were independently associated with THTF. When sum of SUVmax was grouped into quartile ranges, there was a significantly worse survival probability for patients in the fourth-quartile range than in the first, with a univariate hazard ratio of 6.2 (95% CI, 2.8-13.6; P < 0.001). Conclusion: Sum of SUVmax and number of lesions derived from 18F-FDG PET/CT provide independent prognostic information on THTF in men with metastatic castration-sensitive prostate cancer.
| S-EPMC6836859 | biostudies-literature
Project description:ObjectivesWhole body [18F]-fluorodihydrotestosterone positron emission tomography ([18F]FDHT PET) imaging directly targets the androgen receptor and is a promising prognostic and predictive biomarker in metastatic castration-resistant cancer (mCRPC). To optimize [18F]FDHT PET-CT for diagnostic and response assessment purposes, we assessed how count statistics and reconstruction protocol affect its accuracy, repeatability, and lesion detectability.MethodsWhole body [18F]FDHT PET-CT scans were acquired on an analogue PET-CT on two consecutive days in 14 mCRPC patients harbouring a total of 336 FDHT-avid lesions. Images were acquired at 45 min post-injection of 200 MBq [18F]FDHT at 3 min per bed position. List-mode PET data were split on a count-wise basis, yielding two statistically independent scans with each 50% of counts. Images were reconstructed according to current EANM Research Ltd. (EARL1, 4 mm voxel) and novel EARL2 guidelines (4 mm voxel + PSF). Per lesion, we measured SUVpeak, SUVmax, SUVmean, and contrast-to-noise ratio (CNR). SUV was normalized to dose per bodyweight as well as to the parent plasma input curve integral. Variability was assessed with repeatability coefficients (RCs).ResultsCount reduction increased liver coefficient of variation from 9.0 to 12.5% and from 10.8 to 13.2% for EARL1 and EARL2, respectively. SUVs of EARL2 images were 12.0-21.7% higher than EARL1. SUVs of 100% and 50% count data were highly correlated (R2 > 0.98; slope = 0.97-1.01; ICC = 0.99-1.00). Intrascan variability was volume-dependent, and count reduction resulted in higher intrascan variability for EARL2 than EARL1 images. Intrascan RCs were lowest for SUVmean (8.5-10.6%), intermediate for SUVpeak (12.0-16.0%), and highest for SUVmax (17.8-22.2%). Count reduction increased test-retest variance non-significantly (p > 0.05) for all SUV types and normalizations. For SUVpeak at 50% of counts, RCs remained < 30% when small lesions were excluded. Splitting data reduced CNR by median 4.6% (interquartile range 1.2-8.7%) and 4.6% (interquartile range 1.2-8.7%) for EARL1 and EARL2 images, respectively.ConclusionsReducing [18F]FDHT PET acquisition time from 3 min to 1.5 per bed position resulted in a repeatability of SUVpeak (bodyweight) remaining ≤ 30%, which is generally acceptable for response monitoring purposes. However, EARL2 reconstruction was more affected, especially for SUVmax whose repeatability tended to exceed 30%. Lesion detectability was only slightly impaired by reducing acquisition time, which might not be clinically relevant in mCRPC.
| S-EPMC6667590 | biostudies-literature
Project description:Imaging with novel PET radiotracers has significantly influenced radiotherapy decision making and radiation planning in patients with recurrent prostate cancer (PCa). The purpose of this analysis was to report the final results for management decision changes based on 18F-fluciclovine PET/CT findings and determine whether the decision change trend remained after completion of accrual. Methods: Patients with detectable prostate-specific antigen (PSA) after prostatectomy were randomized to undergo either conventional imaging (CI) only (arm A) or CI plus 18F-fluciclovine PET/CT (arm B) before radiotherapy. In arm B, positivity rates on CI and 18F-fluciclovine PET/CT for detection of recurrent PCa were determined. Final decisions on whether to offer radiotherapy and whether to include only the prostate bed or also the pelvis in the radiotherapy field were based on 18F-fluciclovine PET/CT findings. Radiotherapy decisions before and after 18F-fluciclovine PET/CT were compared. The statistical significance of decision changes was determined using the Clopper-Pearson (exact) binomial method. Prognostic factors were compared between patients with and without decision changes. Results: All 165 patients enrolled in the study had standard-of-care CI and were initially planned to receive radiotherapy. Sixty-three of 79 (79.7%) patients (median PSA, 0.33 ng/mL) who underwent 18F-fluciclovine PET/CT (arm B) had positive findings. 18F-Fluciclovine PET/CT had a significantly higher positivity rate than CI did for the whole body (79.7% vs. 13.9%; P < 0.001), prostate bed (69.6% vs. 5.1%; P < 0.001), and pelvic lymph nodes (38.0% vs. 10.1%; P < 0.001). Twenty-eight of 79 (35.4%) patients had the overall radiotherapy decision changed after 18F-fluciclovine PET/CT; in 4 of 79 (5.1%), the decision to use radiotherapy was withdrawn because of extrapelvic disease detected on 18F-fluciclovine PET/CT. In 24 of 75 (32.0%) patients with a final decision to undergo radiotherapy, the radiotherapy field was changed. Changes in overall radiotherapy decisions and radiotherapy fields were statistically significant (P < 0.001). Overall, the mean PSA at PET was significantly different between patients with and without radiotherapy decision changes (P = 0.033). Conclusion: 18F-Fluciclovine PET/CT significantly altered salvage radiotherapy decisions in patients with recurrent PCa after prostatectomy. Further analysis to determine the impact of 18F-fluciclovine PET/CT guidance on clinical outcomes after radiotherapy is in progress.
| S-EPMC8833876 | biostudies-literature
Project description:Quantitative evaluation of radiolabeled prostate-specific membrane antigen (PSMA) PET scans may be used to monitor treatment response in patients with prostate cancer (PCa). To interpret longitudinal differences in PSMA uptake, the intrinsic variability of tracer uptake in PCa lesions needs to be defined. The aim of this study was to investigate the repeatability of quantitative PET/CT measurements using 18F-DCFPyL ([2-(3-(1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid], a second-generation 18F-PSMA-ligand) in patients with PCa. Methods: Twelve patients with metastatic PCa were prospectively included, of whom 2 were excluded from final analyses. Patients received 2 whole-body 18F-DCFPyL PET/CT scans (median dose, 317 MBq; uptake time, 120 min) within a median of 4 d (range, 1-11 d). After semiautomatic (isocontour-based) tumor delineation, the following lesion-based metrics were derived: mean, peak, and maximum tumor-to-blood ratio; SUVmean, SUVpeak, and SUVmax normalized to body weight; tumor volume; and total lesion uptake (TLU). Additionally, patient-based total tumor volume (TTV) (sum of PSMA-positive tumor volumes) and total tumor burden (TTB) (sum of all lesion TLUs) were derived. Repeatability was analyzed using repeatability coefficients (RC) and intraclass correlation coefficients. Additionally, the effect of point-spread function (PSF) image reconstruction on the repeatability of uptake metrics was evaluated. Results: In total, 36 18F-DCFPyL PET-positive lesions were analyzed (≤5 lesions per patient). The RCs for mean, peak, and maximum tumor-to-blood ratio were 31.8%, 31.7%, and 37.3%, respectively. For SUVmean, SUVpeak, and SUVmax, the RCs were 24.4%, 25.3%, and 31.0%, respectively. All intraclass correlation coefficients were at least 0.97. Tumor volume delineations were quite repeatable, with an RC of 28.1% for individual lesion volumes and 17.0% for TTV. TTB had an RC of 23.2% and 33.4% when based on SUVmean and mean tumor-to-blood ratio, respectively. Small lesions (<4.2 cm3) had worse repeatability for volume measurements. The repeatability of SUVpeak, TLU, and all patient-level metrics was not affected by PSF reconstruction. Conclusion: 18F-DCFPyL uptake measurements are quite repeatable and can be used for clinical validation in future treatment response assessment studies. Patient-based TTV may be preferred for multicenter studies because its repeatability was both high and robust to different image reconstructions.
| S-EPMC7456167 | biostudies-literature
Project description:BackgroundStereotactic radiosurgery (SRS) is often the primary treatment modality for patients with intracranial metastatic disease. Despite advances in magnetic resonance imaging, including use of perfusion and diffusion sequences and molecular imaging, distinguishing radiation necrosis from progressive tumor remains a diagnostic and clinical challenge. We investigated the sensitivity and specificity of 18F-fluciclovine PET to accurately distinguish radiation necrosis from recurrent intracranial metastatic disease in patients who had previously undergone SRS.MethodsFluciclovine PET imaging was performed in 8 patients with a total of 15 lesions that had previously undergone SRS and had subsequent MRI and clinical features suspicious for recurrent disease. The SUVmax of each lesion and the contralateral normal brain parenchyma were summated and evaluated at four different time points (5 min, 10 min, 30 min, and 55 min). Lesions were characterized as either recurrent disease (11 of 15 lesions) or radiation necrosis (4 of 15 lesions) and confirmed with histopathological correlation (7 lesions) or through serial MRI studies (8 lesions).ResultsTime activity curve analysis found statistically greater radiotracer accumulation for all lesions, including radiation necrosis, when compared to contralateral normal brain. While the mean and median SUVmax for recurrent disease were statistically greater than those of radiation necrosis at all time points, the difference was more significant at the earlier time points (p = 0.004 at 5 min-0.025 at 55 min). Using a SUVmax threshold of ≥ 1.3, fluciclovine PET demonstrated a 100% accuracy in distinguishing recurrent disease from radiation necrosis up to 30 min after injection and an accuracy of 87% (sensitivity = 0.91, specificity = 0.75) at the last time point of 55 min. However, tumor-to-background ratios (TBRmax) were not significantly different between recurrent disease and radiation necrosis at any time point due to variable levels of fluciclovine uptake in the background brain parenchyma.ConclusionsFluciclovine PET may play an important role in distinguishing active intracranial metastatic lesions from radiation necrosis in patients previously treated with SRS but needs to be validated in larger studies.
| S-EPMC7721921 | biostudies-literature
Project description:Purpose[18F]FDG PET/CT in multiple myeloma (MM) is currently the best technology to demonstrate patchy and extramedullary disease. However, [18F]FDG PET has some limitations, and imaging with alternative tracers should be explored. In this study, we aimed to evaluate the performance of [18F]fluciclovine PET compared to [18F]FDG PET in newly diagnosed MM patients.ProceduresThirteen newly diagnosed transplant eligible MM patients were imaged both with [18F]FDG PET/CT and [18F]fluciclovine PET/CT within 1 week in a prospective study. The subjects were visually assessed positive or negative for disease. The number of lesions and the SUVmax of selected lesions were measured for both tracers. Furthermore, tracer uptake ratios were obtained by dividing lesion SUVmax by blood or bone marrow SUVmax. Between-group differences and correlations were assessed with paired t-tests and Pearson tests. Bone marrow SUVs were compared to bone marrow plasma cell percentage in biopsy samples.ResultsNine subjects were assessed positively by [18F]FDG PET (69%) and 12 positives by [18F]fluciclovine PET (92%). All positive subjects had [18F]fluciclovine scans that were qualitatively scored as easier to interpret visually than the [18F]FDG scans. The number of lesions was also higher; seven of nine subjects with distinct hot spots on [18F]fluciclovine PET had fewer or no visible lesions on [18F]FDG PET. The mean lesion SUVmax values were 8.2 and 3.8 for [18F]fluciclovine and [18F]FDG, respectively. The mean tumour to blood values were 6.4 and 2.0 for [18F]fluciclovine and [18F]FDG, and the mean ratios between tumour and bone marrow were 2.1 and 1.5 for [18F]fluciclovine and [18F]FDG. The lesion SUVmax and ratios were significantly higher for [18F]fluciclovine (all p < 0.01). Local [18F]fluciclovine SUVmax or SUVmean values in os ilium and the percentage of plasma cells in bone marrow biopsies were linearly correlated (p = 0.048). There were no significant correlations between [18F]FDG SUVs and plasma cells (p = 0.82).ConclusionsBased on this pilot study, [18F]fluciclovine is a promising tracer for MM. The visual and semi-quantitative evaluations indicate that [18F]fluciclovine PET/CT can out-perform [18F]FDG PET/CT at diagnosis.
| S-EPMC9581841 | biostudies-literature
Project description:The purpose of this study was to evaluate 18F-fluciclovine PET/CT detection rates in the evaluation of biochemical recurrence in prostate cancer patients with very low (≤0.3 ng/mL) serum prostate-specific antigen (PSA) levels following definitive treatment. Prostate cancer patients with biochemical recurrence and very low serum PSA (≤0.3 ng/mL) who underwent clinical 18F-fluciclovine PET/CT were included in this single-institution retrospective study. PET/CT clinical reports at the time of interpretation were reviewed and categorized as positive or negative. In patients who had further evaluation with imaging and/or biopsy, the results were recorded to determine the true detection rate. Of the 64 eligible patients with very low serum PSA (median serum PSA of 0.17 ng/mL), 57.8% (37/64) scans were categorized as positive. Stratified by PSA levels, positivity rates were 43.8% (7/16), 60.0% (15/25) and 65.2% (15/23) for PSA<0.1 ng/mL, 0.1-<0.2 ng/mL and 0.2-≤0.3 ng/mL, respectively. The most common location of disease was the prostate bed (73%), followed by pelvic lymph nodes (22%) and distant disease (14%). In the small subset of patients who had further evaluation after a positive study (n=7), all had confirmed disease with a positive predictive value of 100%. In conclusion, among prostate cancer patients with biochemical recurrence, 18F-fluciclovine PET/CT is useful in patients with very low serum PSA of ≤0.3 ng/mL, with a 57.8% positivity rate, higher than previously reported. Though standard of truth could only be ascertained in 19% (7/37) of patients with a positive study, the positive predictive value was 100%.
| S-EPMC8569337 | biostudies-literature
Project description:The present explorative study was initiated to evaluate the clinical value of 18F-FES PET/CT in monitoring the change of estrogen receptor (ER) expression and potential predictive value in metastatic breast cancer patients. Twenty-two pathology-confirmed breast cancer patients were prospectively enrolled and randomly divided into two groups (T: docetaxel, n = 14 and TF: docetaxel + fulvestrant, n = 8). The percentage of patients without disease progression after 12 months (PFS > 12 months) was 62.5% in group TF compared with 21.4% in group T (P = 0.08). According to 18F-FES PET/CT scans, the SUVmax (maximum standard uptake value) of all the metastatic lesions decreased in group TF after 2 cycles of treatment (6 weeks ± 3 days). However, 6 of 9 patients in group T had at least one lesion with higher post-treatment SUVmax. There was a significant difference in the reduction of ER expression between these two groups (P = 0.028). In group TF, the patients with PFS > 12 months had significantly greater SUVmax changes of 18F-FES than those with PFS < 12 months (PFS > 12 months: 91.0 ± 12.0% versus PFS < 12 months: 20.7 ± 16.2%; t = -4.64, P = 0.01). Our preliminary study showed that 18F-FES PET/CT, as a noninvasive method to monitor ER expression, could be utilized to predict prognosis based on changes in SUVmax.
| S-EPMC5529439 | biostudies-literature