Real-world evidence of 18F-fluciclovine Positron emission tomography/computed tomography performance for recurrent prostate cancer in the Veterans Affairs Health System.

BACKGROUND: There are no population-level studies assessing 18F-fluciclovine (fluciclovine) utilization of Positron emission tomography/computed tomography (PET/CT) for biochemically recurrent prostate cancer (PC). We assessed fluciclovine PET/CT in the Veterans Affairs Health Care System. METHODS: Of 1153 men with claims suggesting receipt of fluciclovine PET/CT, we randomly reviewed charts of 300 who indeed underwent fluciclovine PET/CT. The primary outcome was fluciclovine PET/CT result (positive or negative). Comparison among groups stratified by androgen deprivation therapy (ADT) (yes vs. no) and prostate-specific antigen (PSA) (≤1 vs. >1 ng/mL) at imaging were performed. Logistic regression tested associations between PSA, ADT receipt, and race with fluciclovine PET/CT positive imaging. RESULTS: Fluciclovine PET/CT positivity rate was 33% for patients with PSA 0-0.5 ng/mL, 21% for >0.5-1.0, 54% for >1.0-2.0, and 66% for >2.0 (p < 0.01). A 59% positivity rate ocurred in patients treated with concurrent ADT versus 37% in those not on ADT (p < 0.01). White were more likely to have a positive scan versus Black patients (55% vs. 38%; p = 0.02). Patients whose primary treatment was radical prostatectomy had a lower positivity rate (33%) versus those treated with radiotherapy (55%) (p < 0.001). On multivariable logistic regression, PSA > 1 ng/mL (all men odds ratio [OR]: 4.06, 95% confidence interval [CI]: 2.07-7.96; men on ADT only OR: 4.42, 95% CI: 1.73-11.26) and use of ADT (OR: 3.94, 95% CI: 1.32-11.75), and White (all men OR: 2.22, 95% CI: 1.20-4.17) predicted positive fluciclovine PET/CT. CONCLUSION: This real-world study assessing 18F-fluciclovine PET/CT performance in an equal access health care system confirms higher detection rates than traditional imaging methods, but positivity is highly influenced by PSA at time of imaging. Additionally, patients currently receiving ADT have at least four times higher likelihood of a positive scan, showing that scan positivity isn't negatively affected by ADT status in this study. Finally, White men were more likely to have a positive scan, the reasons for which should be explored in future studies.

Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.

PURPOSE: To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT]. METHODS: 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test. RESULTS: The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021]. CONCLUSION: In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study. CLINICAL TRIAL REGISTRATION: Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).

Assessing the effectiveness of MRI, 18F-fluciclovine PET, SUVmax, and PSA in detecting local recurrence of prostate cancer after prostatectomy.

Purpose: The primary objective of this study was to evaluate the discriminatory utility of magnetic resonance imaging (MRI), 18F-fluciclovine positron emission tomography (PET), maximum standardized uptake value (SUVmax), prostate-specific antigen (PSA), and combinations of these diagnostic modalities for detecting local prostate cancer recurrence in the setting of rising PSA after radical prostatectomy. Material and methods: Patients were characterised for clinical features such as Gleason score, PSA at surgery, PSA at follow-up, follow-up MRI result, follow-up PET result, follow-up SUVmax, and follow-up disease status. The utility of diagnostic parameters for detecting disease recurrence at the prostatectomy bed was assessed using receiver operating characteristics (ROC) analysis to determine the area under the curve (AUC) for each model. Sensitivity, specificity, and positive/negative predictive values were also calculated. Optimal cut-off points for continuous variables were determined based on maximum Youden's J statistics. Results: The study found that MRI had the highest concordance (96%), sensitivity (100%), specificity (91%), positive predictive value (93%), and negative predictive value (100%) among the diagnostic modalities. The AUC for MRI was 0.9545, indicating a high discriminatory ability for detecting prostate cancer local recurrence. When combined, PET and SUVmax (cut-off value of 2.85) showed an improved performance compared to using them individually, with an AUC of 0.8925. Conclusions: The analysis suggests that MRI is the most effective imaging modality for detecting local prostate cancer recurrence, with 18F-fluciclovine PET and SUVmax also showing promising combined results. PSA has moderate discriminatory utility at follow-up but can still provide valuable information in detecting prostate cancer recurrence. Further research and recent references are needed to support these findings.

18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

PSA and PSA Kinetics as Predictors for 18F-Fluciclovine PET/CT Positivity in Biochemically Recurrent Prostate Cancer.

INTRODUCTION: 18F-Fluciclovine PET/CT is one of the imaging techniques currently employed to restage prostate cancer (PCa). Due to the conflicting results reported in the literature, it is not yet known at what PSA threshold 18F-fluciclovine PET/CT could reliably demonstrate the presence of recurring disease. We explored the association between 18F-fluciclovine PET/CT positivity and prescan PSA, PSA doubling time, and PSA velocity in patients with biochemical recurrence (BCR) of PCa after curative-intent treatment. METHODS: Data from 59 patients who underwent 18F-fluciclovine PET/CT for BCR after radical prostatectomy or radiotherapy were retrieved from a single institution database. Patients already undergone salvage treatments at the time of PET/CT, with newly diagnosed PCa or with initial diagnosis of metastatic PCa were excluded. A 2-sided independent samples Bayesian t test and Bayesian Mann-Whitney U test were used to assess the association between PET/CT and prescan PSA, PSA doubling time, and PSA velocity. RESULTS: Evidence for no difference between PET/CT-positive and -negative patients for log-transformed PSA was found (BF01 3.61, % error: 0.01). Robustness check and sequential analysis showed stability across a wide range of prior distribution specifications. The hypothesis of no difference in terms of PSA-dt and for PSA-vel between groups was found to be more likely compared to the alternative hypothesis (BF01 of 3.44 and 3.48, respectively). CONCLUSION: PSA and PSA kinetics are unlikely to be associated with 18F-fluciclovine PET/CT positivity in patients with BCR, and none of these serum biomarkers might be used as single predictors of PET/CT detection. Larger studies might be needed to evaluate the role of different predictors.

[18F]-Fluciclovine PET/CT for preoperative nodal staging in high-risk primary prostate cancer: final results of a prospective trial.

PURPOSE: The conventional imaging flowchart for prostate cancer (PCa) staging may fail in correctly detecting lymph node metastases (LNM). Pelvic lymph node dissection (PLND) represents the only reliable method, although invasive. A new amino acid PET compound, [18F]-fluciclovine, was recently authorized in suspected PCa recurrence but not yet included in the standard staging work-up of primary PCa. A prospective monocentric study was designed to evaluate [18F]-fluciclovine PET/CT diagnostic performance for preoperative LN staging in primary high-risk PCa. METHODS: Consecutive patients (pts) with biopsy-proven PCa, standard staging (including [11C]choline PET/CT), eligible for PLND, were enrolled to undergo an investigational [18F]-fluciclovine PET/CT. Nodal uptake higher than surrounding background was reported by at least two readers (blinded to [11C]choline) using a visual 5-point scale (1-2 probably negative; 4-5 probably positive; 3 equivocal); SUVmax, target-to-background (aorta-A; bone marrow-BM) ratios (TBRs), were also calculated. PET results were validated with PLND. [18F]-fluciclovine PET/CT performance using visual score and semi-quantitative indexes was analyzed both per patient and per LN anatomical region, compared to conventional [11C]choline and clinical predictive factors (to note that diagnostic performance of [18F]-fluciclovine was explored for LNM but not examined for intrapelvic or extrapelvic M1 lesions). RESULTS: Overall, 94 pts underwent [18F]-fluciclovine PET/CT; 72/94 (77%) high-risk pts were included in the final analyses (22 pts excluded: 8 limited PLND; 3 intermediate-risk; 2 treated with radiotherapy; 4 found to be M1; 5 neoadjuvant hormonal therapy). Median LNM risk by Briganti nomogram was 19%. LNM confirmed on histology was 25% (18/72 pts). Overall, 1671 LN were retrieved; 45/1671 (3%) LNM detected. Per pt, median no. of removed LN was 22 (mean 23 ± 10; range 8-51), of LNM was 2 (mean 3 ± 2; range 1-10). Median LNM size was 5 mm (mean 5 ± 2.5; range 2-10). On patient-based analyses (n = 72), diagnostic performance for LNM resulted significant with [18F]-fluciclovine (AUC 0.66, p 0.04; 50% sensitivity, 81% specificity, 47% PPV, 83% NPV, 74% accuracy), but not with [11C]choline (AUC 0.60, p 0.2; 50%, 70%, 36%, 81%, and 65% respectively). Briganti nomogram (OR = 1.03, p = 0.04) and [18F]-fluciclovine visual score (≥ 4) (OR = 4.27, p = 0.02) resulted independent predictors of LNM at multivariable analyses. On region-based semi-quantitative analyses (n = 576), PET/CT performed better using TBR parameters (TBR-A similar to TBR-BM; TBR-A fluciclovine AUC 0.61, p 0.35, vs choline AUC 0.57 p 0.54; TBR-BM fluciclovine AUC 0.61, p 0.36, vs choline AUC 0.58, p 0.52) rather than using absolute LN SUVmax (fluciclovine AUC 0.51, p 0.91, vs choline AUC 0.51, p 0.94). However, in all cases, diagnostic performance was not statistically significant for LNM detection, although slightly in favor of the experimental tracer [18F]-fluciclovine for each parameter. On the contrary, visual interpretation significantly outperformed PET semi-quantitative parameters (choline and fluciclovine: AUC 0.65 and 0.64 respectively; p 0.03) and represents an independent predictive factor of LNM with both tracers, in particular [18F]-fluciclovine (OR = 8.70, p 0.002, vs OR = 3.98, p = 0.03). CONCLUSION: In high-risk primary PCa, [18F]-fluciclovine demonstrates some advantages compared with [11C]choline but sensitivity for metastatic LN detection is still inadequate compared to PLND. Visual (combined morphological and functional), compared to semi-quantitative assessment, is promising but relies mainly on readers' experience rather than on unquestionable LN avidity. TRIAL REGISTRATION: EudraCT number: 2014-003,165-15.

A bicentric retrospective analysis of clinical utility of 18F-fluciclovine PET in biochemically recurrent prostate cancer following primary radiation therapy: is it helpful in patients with a PSA rise less than the Phoenix criteria?

PURPOSE: 18F-Fluciclovine PET imaging has been increasingly used in the restaging of prostate cancer patients with biochemical recurrence (BCR); however, its clinical utility in patients with low prostate-specific antigen (PSA) levels following primary radiation therapy has not been well-studied. This study aims to determine the detection rate and diagnostic accuracy of 18F-fluciclovine PET and the patterns of prostate cancer recurrence in patients with rising PSA after initial radiation therapy, particularly in patients with PSA levels below the accepted Phoenix definition of BCR (PSA nadir +2 ng/mL). METHODS: This retrospective study included patients from two tertiary institutions who underwent 18F-fluciclovine PET scans for elevated PSA level following initial external beam radiation therapy, brachytherapy, and/or proton therapy. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic accuracy of 18F-fluciclovine PET and associations of PSA kinetic parameters with 18F-fluciclovine PET outcome. RESULTS: One hundred patients were included in this study. The overall detection rate on a patient-level was 79% (79/100). 18F-Fluciclovine PET was positive in 62% (23/37) of cases with PSA below the Phoenix criteria. The positive predictive value of 18F-fluciclovine PET was 89% (95% CI: 80-94%). In patients with PSA below the Phoenix criteria, the PSA velocity had the highest predictive value of 18F-fluciclovine PET outcome. PSA doubling time (PSADT) and PSA velocity were associated with the presence of extra-pelvic metastatic disease. CONCLUSION: 18F-Fluciclovine PET can identify recurrent disease at low PSA level and PSA rise below accepted Phoenix criteria in patients with suspected BCR after primary radiation therapy, particularly in patients with low PSADT or high PSA velocity. In patients with low PSADT or high PSA velocity, there is an increased probability of extra-pelvic metastases. Therefore, these patients are more likely to benefit from PET/CT or PET/MRI than pelvic MRI alone.

Utility of 18F-Fluciclovine PET/MRI for Staging Newly Diagnosed High-Risk Prostate Cancer and Evaluating Response to Initial Androgen Deprivation Therapy: A Prospective Single-Arm Pilot Study.

BACKGROUND. Despite advances in prostate cancer treatment, rates of biochemical recurrence remain high, relating to lack of detection of small-volume metastatic disease using conventional imaging for initial staging. OBJECTIVE. The purpose of this study was to assess the potential use of 18F-fluciclovine PET/MRI for initial staging of high-risk prostate cancer and evaluating response to androgen deprivation therapy (ADT). METHODS. This prospective clinical trial enrolled 14 men with newly diagnosed high-risk prostate cancer and negative or equivocal conventional staging imaging for metastatic disease between January 2018 and February 2019. All patients underwent pretreatment 18F-fluciclovine PET/MRI including multiparametric prostate MRI; 12 underwent 18F-fluciclovine PET/MRI after surgery or between ADT and radiotherapy. Confidence in identification of the primary intraprostatic lesion and nodal metastases was independently rated on a 0-3 Likert scale by three readers with nuclear medicine experience for 18F-fluciclovine PET/MRI and three readers with abdominal imaging experience for MRI alone. Findings scored as 2 or 3 by at least two readers of a given modality were considered positive. A single reader measured SUVmean, SUVmax, and volume of the MRI-defined intraprostatic lesion and SUVmax of suspicious lymph nodes on PET before and after initiation of ADT. Changes in SUV were analyzed using nonparametric Wilcox-on signed-rank tests. RESULTS. The biopsy-proven lesion in the prostate gland was accurately identified in all 14 patients on both MRI and 18F-fluciclovine PET/MRI. Suspected nodal metastases were detected in three patients on MRI and seven patients on 18F-fluciclovine PET/MRI. After ADT, all patients showed decreased activity within the intraprostatic lesion and/or all suspicious lymph nodes. The primary lesion SUVmean was 4.5 ± 1.1 (range, 2.7-6.5) before treatment and 2.4 ± 1.1 (range, 0.0-3.6) after initiation of ADT (p = .008). For suspicious lymph nodes, the pretreatment SUVmax was 5.5 ± 3.7 (range, 2.8-12.7) and the post-treatment SUVmax was 2.8 ± 1.4 (range, 1.4-5.5) (p = .03). CONCLUSION.18F-labeled fluciclovine PET/MRI shows potential utility in initial staging of high-risk prostate cancer and in evaluating response to ADT. CLINICAL IMPACT. Given the FDA approval and widespread availability of 18F-fluciclovine, the findings could have an impact in the immediate future in guiding initial management of patients with prostate cancer. TRIAL REGISTRATION. ClinicalTrials.gov NCT03264456.

Role of 18F-Fluciclovine and Prostate-Specific Membrane Antigen PET/CT in Guiding Management of Oligometastatic Prostate Cancer: AJR Expert Panel Narrative Review.

Twenty-five years ago, oligometastatic disease was proposed as an intermediary clinical state of cancer with unique implications for therapies that may impact cancer evolution and patient outcome. Identification of limited metastases that are potentially amenable to targeted therapies fundamentally depends on the sensitivity of diagnostic tools, including new-generation imaging methods. For men with biochemical recurrence after definitive therapy of the primary prostate cancer, PET/CT using either the FDA-approved radiolabeled amino acid analogue 18F-fluciclovine or investigational radiolabeled agents targeting prostate-specific membrane antigen (PSMA) enables identification of early metastases at lower serum PSA levels than was previously feasible using conventional imaging. Evidence supports PSMA PET/CT as the most sensitive imaging modality available for identifying disease sites in oligometastatic prostate cancer. PSMA PET/CT will likely become the modality of choice after regulatory approval and will drive the development of trials of emerging metastasis-directed therapies such as stereotactic ablative body radiation and radioguided surgery. Indeed, numerous ongoing or planned clinical trials are studying advances in management of oligometastatic prostate cancer based on this heightened diagnostic capacity. In this rapidly evolving clinical environment, radiologists and nuclear medicine physicians will play major roles in facilitating clinical decision making and management of patients with oligometastatic prostate cancer.

[18F]Fluciclovine Positron Emission Tomography/Computerized Tomography for Preoperative Staging in Patients with Intermediate to High Risk Primary Prostate Cancer.

PURPOSE: Accurate preoperative staging of prostate cancer is essential for treatment planning. Conventional imaging is limited in detection of metastases. Our primary aim was to determine if [18F]fluciclovine positron emission tomography/computerized tomography is an early indicator of subclinical metastasis among patients with high risk prostate cancer. MATERIALS AND METHODS: A total of 68 patients with unfavorable intermediate to very high risk prostate cancer without systemic disease on conventional imaging were recruited before robotic radical prostatectomy with extended pelvic lymph node dissection. Diagnostic performance of [18F]fluciclovine positron emission tomography/computerized tomography and conventional imaging for detection of metastatic disease, and correlation of positivity to node and metastatic deposit size were determined. RESULTS: Overall 57 of 68 patients completed the protocol, of whom 31 had nodal metastasis on histology. [18F]Fluciclovine positron emission tomography/computerized tomography sensitivity and specificity in detecting nodal metastasis was 55.3% and 84.8% per patient, and 54.8% and 96.4% per region (right and left pelvis, presacral and nonregional), respectively. Compared with conventional imaging [18F]Fluciclovine positron emission tomography/computerized tomography had significantly higher sensitivity on patient based (55.3% vs 33.3%, p <0.01) and region based (54.8% vs 19.4%, p <0.01) analysis, detecting metastasis in 7 more patients and 22 more regions, with similar high specificity. Four additional patients had distant disease or other cancer detected on [18F] fluciclovine positron emission tomography/computerized tomography which precluded surgery. Detection of metastasis was related to size of metastatic deposits within lymph nodes and overall metastatic burden. CONCLUSIONS: [18F]Fluciclovine positron emission tomography/computerized tomography detects occult metastases not identified on conventional imaging and may help guide treatment decisions and lymph node dissection due to high specificity for metastatic disease.

Performance of 18F-fluciclovine PET/MR in the evaluation of osseous metastases from castration-resistant prostate cancer.

PURPOSE: 18F-Fluciclovine is indicated for evaluation of suspected prostate cancer (PCa) biochemical recurrence. There are few studies investigating fluciclovine with PET/MR and none evaluated osseous metastases. Our aim was to assess the performance of 18F-fluciclovine PET/MR (fluciclovine-PET/MR) for detecting osseous metastases in patients with castration-resistant prostate cancer (CRPC). We also investigated possible correlations between SUVmax and ADCmean. METHODS: We evaluated 8 patients with CRPC metastatic to bones, some before and some after radium therapy, who underwent 13 fluciclovine-PET/MR studies. We analyzed the performance of radionuclide bone scan (RBS), MR alone, fluciclovine-PET alone, and fluciclovine-PET/MR in detecting osseous metastases. Lesion size, characteristics (early sclerotic, late sclerotic, mixed, lytic), SUVmax, and ADCmean were assessed. The reference standard was a combination of clinical information and correlation with both prior and follow-up imaging. RESULTS: Of 347 metastatic bony lesions in 13 studies, 238/347 (68%) were detected by fluciclovine-PET alone, 286/347 (82%) by RBS, 344/347 (99%) by MR alone, and 347/347 (100%) by fluciclovine-PET/MR. Fluciclovine-PET/MR and MR had the best performance (p < 0.001). There was no statistically significant difference between fluciclovine-PET/MR and MR alone (p = 0.25). Fluciclovine-PET had a lower detection rate especially with late sclerotic lesions (p < 0.001). There was a moderate inverse correlation between lesion SUVmax and ADCmean (r = - 0.49; p < 0.001). CONCLUSIONS: This study suggests that fluciclovine-PET/MR and MR have high sensitivity for detecting osseous metastases in CRPC. Fluciclovine-PET alone underperformed in detecting late sclerotic lesions. The inverse correlation between SUVmax and ADCmean suggests a possible relationship between tumor metabolism and cellularity.

Deep learning detection of prostate cancer recurrence with 18F-FACBC (fluciclovine, Axumin®) positron emission tomography.

PURPOSE: To evaluate the performance of deep learning (DL) classifiers in discriminating normal and abnormal 18F-FACBC (fluciclovine, Axumin®) PET scans based on the presence of tumor recurrence and/or metastases in patients with prostate cancer (PC) and biochemical recurrence (BCR). METHODS: A total of 251 consecutive 18F-fluciclovine PET scans were acquired between September 2017 and June 2019 in 233 PC patients with BCR (18 patients had 2 scans). PET images were labeled as normal or abnormal using clinical reports as the ground truth. Convolutional neural network (CNN) models were trained using two different architectures, a 2D-CNN (ResNet-50) using single slices (slice-based approach) and the same 2D-CNN and a 3D-CNN (ResNet-14) using a hundred slices per PET image (case-based approach). Models' performances were evaluated on independent test datasets. RESULTS: For the 2D-CNN slice-based approach, 6800 and 536 slices were used for training and test datasets, respectively. The sensitivity and specificity of this model were 90.7% and 95.1%, and the area under the curve (AUC) of receiver operating characteristic curve was 0.971 (p < 0.001). For the case-based approaches using both 2D-CNN and 3D-CNN architectures, a training dataset of 100 images and a test dataset of 28 images were randomly allocated. The sensitivity, specificity, and AUC to discriminate abnormal images by the 2D-CNN and 3D-CNN case-based approaches were 85.7%, 71.4%, and 0.750 (p = 0.013) and 71.4%, 71.4%, and 0.699 (p = 0.053), respectively. CONCLUSION: DL accurately classifies abnormal 18F-fluciclovine PET images of the pelvis in patients with BCR of PC. A DL classifier using single slice prediction had superior performance over case-based prediction.

[18F]Fluciclovine PET/CT: joint EANM and SNMMI procedure guideline for prostate cancer imaging-version 1.0.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [18F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [18F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors.

PURPOSE: The aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection. METHODS: Twenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI. RESULTS: 18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5 ± 2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0 ± 2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p < 0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5 ± 0.2 compared to 1.3 ± 0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7 ± 2.3 h), and achieving a consistent final distribution volume averaging 1.4 ± 0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57 ± 51 min), with an average distribution volume of 3.2 ± 1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine. CONCLUSION: Tumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.

Utility of 18F-Fluciclovine PET/CT for Detecting Prostate Cancer Recurrence in Patients With Low (< 1 ng/mL) or Very Low (< 0.3 ng/mL) Prostate-Specific Antigen Levels.

OBJECTIVE. We reviewed a retrospective series of 126 18F-fluciclovine PET/CT studies of patients with biochemically recurrent prostate cancer at low (< 1 ng/mL) and very low (< 0.3 ng/mL) prostate-specific antigen (PSA) levels. CONCLUSION. The rate of PET/CT positivity was 33% (15/46) in patients with low PSA levels and 0% (0/17) in patients with very low PSA levels. Our results suggest that 18F-fluciclovine PET/CT can be helpful for localizing recurrence in patients with PSA levels between 0.3 and 1 ng/mL and that 18F-fluciclovine PET/CT is not recommended in patients with PSA levels less than 0.3 ng/mL.

Fluorine-18-Labeled Fluciclovine PET/CT in Primary and Biochemical Recurrent Prostate Cancer Management.

OBJECTIVE. The purpose of this article is to review the utility of 18F-fluciclovine PET/CT in the evaluation of recurrent prostate cancer. CONCLUSION. Fluorine-18-labeled fluciclovine PET/CT has shown promise in the evaluation of recurrent prostate cancer. Its performance has been superior to that of other imaging modalities. It has had good diagnostic accuracy, especially in the detection of extra-prostatic disease recurrence, and the findings have an impact on treatment planning. Gallium-68-labeled prostate-specific membrane antigen PET/CT has also had excellent performance in the detection of biochemically recurrent prostate cancer with detection rates superior to those of fluciclovine PET/CT.

Extraprostatic Uptake of 18F-Fluciclovine: Differentiation of Nonprostatic Neoplasms From Metastatic Prostate Cancer.

OBJECTIVE. Fluciclovine is a synthetic radiolabeled amino acid analog used for imaging of biochemical recurrent prostate cancer. Uptake of fluciclovine is mediated by several amino acid transporters, including alanine-serine-cysteine transporter 2 and large neutral amino acid transporters, which are known to be overexpressed in other malignancies. CONCLUSION. Knowledge of the common patterns of prostate cancer recurrence, in addition to what other neoplasms can show uptake, is critical for accurate study interpretation.

Atypical gynecomastia mimicking breast malignancy on mammography, sonography, and 18F-fluciclovine PET/CT in the setting of biochemical recurrence of prostate cancer.

A 60-year-old man with metastatic prostate cancer presented with breast swelling for one year. Suspicious breast masses were identified in both breasts with mammography and ultrasound. Biopsy of both masses showed florid gynecomastia without malignancy. Sixteen months later, the patient underwent 18F-fluciclovine PET/CT for biochemical recurrence of prostate cancer; this showed focal radiotracer uptake in both breasts. Repeat mammogram and ultrasound showed these areas to correspond with the previously biopsied masses, which were stable. To our knowledge, this is the first reported case of gynecomastia mimicking malignancy on 18F-fluciclovine PET/CT.

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Prostate cancer is the most common malignancy tumor among men in developed countries. The incidence rate in recent years is also increasing in China. With the development of technology, the application of PET/CT examination has been augmented in the diagnosis of prostate cancer. In order to detect prostate cancer more safely and effectively, new types of targeted tracer for PET/CT has been developed, including 18F-fluiclovine. 18F-fluiclovine has the characteristics of fast uptake, rapid development and fast metabolism, which has a good diagnostic rate for the recurrence and metastasis of prostate cancer. However, at present, there are few researches and its security, diagnosis efficiency, and application value still need further research to verify.

Fluorine-18-Labeled Fluciclovine PET/CT in Clinical Practice: Factors Affecting the Rate of Detection of Recurrent Prostate Cancer.

OBJECTIVE. The purpose of this study is to show the performance and evaluate the factors influencing the positivity rate (PR) of commercially produced 18F-fluciclovine PET/CT in the detection of recurrent prostate cancer in clinical practice. MATERIALS AND METHODS. We performed a retrospective cohort study of 152 men who had suspected biochemical recurrence of prostate cancer after receiving initial treatment and underwent fluciclovine PET/CT. PRs were calculated for whole-body, prostate and prostate bed, and extraprostatic locations. The influence of different factors, such as the absolute prostate-specific antigen (PSA) level, PSA kinetics, the Gleason score, and Gleason grade groups, on the PR was evaluated. RESULTS. The overall PR was 81% (123/152) for the whole body, 61% (92/152) for the prostate and prostate bed, and 55% (83/152) for extraprostatic locations. There was a linear increase in the PR with an increasing PSA level (p < 0.001). For the whole body, the PR for PSA levels of less than 1 ng/mL, 1 to less than 2 ng/mL, 2 to less than 5 ng/mL, and 5 or more ng/mL were 58% (32/55), 87% (13/15), 100% (39/39), and 92% (35/38), respectively. No statistically significant linear trend was found between the PR and the PSA level doubling time (p > 0.05). In addition, no statistically significant linear trend was found between the PR and increasing Gleason grade group. However, for every 1-unit increase in a patient's Gleason score, the odds of a positive finding in the extraprostatic location increased by 49% (p < 0.05). CONCLUSION. Commercially produced fluciclovine PET/CT has a high PR for detection of prostate cancer recurrence and is positively correlated with increasing PSA levels. For extraprostatic disease, the PR increases with higher Gleason scores.