18F-fluciclovine Positron Emission Tomography Research Articles

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

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. 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. 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. 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.

Exploratory Analysis of Serial 18F-fluciclovine PET-CT and Multiparametric MRI during Chemoradiation for Glioblastoma.

Simple SummaryGlioblastoma (GBM), the most common malignant adult primary brain tumour, has a prognosis of ~12–15 months. Poor prognosis is partly due to the inability to accurately define the extent of tumour infiltration; currently demarcated using magnetic resonance imaging (MRI) sequences (e.g., post-contrast T1-weighted (Gd-T1) and dynamic contrast-enhanced (DCE-MRI)). Anti-1-amino-3-18fluorine-fluorocyclobutane-1-carboxylic acid (18F-fluciclovine) positron emission tomography (PET) may depict GBM better than MRI. This prospective pilot study aimed to explore the relationship of 18F-fluciclovine PET, DCE-MRI and Gd-T1 in patients with GBM undergoing standard-of-care adjuvant chemoradiotherapy. A parallel mouse glioma model was used to investigate the relationship between 18F-fluciclovine PET, MRI and tumour biology. Clinical results showed that GBM volume on 18F-fluciclovine PET tended to be larger than Gd-T1 and DCE-MRI in patients with shorter overall survival (OS) but smaller in patients with longer OS. The preclinical study confirmed that 18F-fluciclovine uptake reflected biologically active tumour. Results suggest that 18F-fluciclovine PET may better define GBM infiltration than MRI.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.

Effect of Androgen Deprivation Therapy on the Results of PET/CT with 18F-Fluciclovine in Patients with Metastatic Prostate Cancer.

Background: 18F-fluciclovine is a positron emission tomography (PET) radiotracer approved for the detection of prostate cancer recurrence. No effect of androgen deprivation therapy (ADT) on its performance has been established. Purpose: To study the impact of concurrent ADT on disease detection with 18F-fluciclovine PET in patients with prostate cancer. Materials and Methods: Data from patients with prostate cancer who had been receiving ADT for ≥3 months at the time of undergoing an 18F-fluciclovine PET/CT at our institution were retrospectively reviewed. Seventy-three scans from 71 patients were included. The scans indicated rising prostate-specific antigen (n = 58), staging advanced disease (n = 4) or therapeutic monitoring (n = 9). Patients’ medical records provided baseline clinical data and post-scan outcomes (median follow-up 40 months). Results: Malignant lesions with increased uptake of 18F-fluciclovine were detected in 60/73 (82%) scans; 33 (45%) had lesions in the prostate/bed and 46 (63%) in extraprostatic sites. Patients received ADT for a median of 2 years (range 3 months to >10 years) pre-scan. The time on ADT did not influence detection; the detection rates were 89% for patients who had received ADT for <1 year, 63% for a treatment period of 1–<2 years, 83% for 2–4 years, 78% for >4–10 years, and 67% for a treatment period of >10 years. Conclusion: 18F-fluciclovine detected recurrent or metastatic lesions in 82% of patients with prostate cancer receiving ADT. The rates achieved in the present study are consistent with widely reported data for 18F-fluciclovine PET/CT, suggesting that withdrawal of ADT before scanning is not necessary.

Validating Modern NRG Oncology Pelvic Nodal and Groupe Francophone de Radiothérapie Urologique Prostate Bed Contouring Guidelines for Post-Prostatectomy Salvage Radiation: A Secondary Analysis of the LOCATE Trial

We used the patterns of recurrence on 18F-fluciclovine positron emission tomography (PET)-computed tomography (CT) in patients enrolled in the LOCATE trial after prostatectomy to evaluate how well the most recent NRG Oncology and Groupe Francophone de Radiothérapie Urologique (GFRU) contouring recommendations encompassed all sites of recurrence in the prostate fossa and pelvic nodes in comparison to former Radiation Therapy Oncology Group (RTOG) recommendations. Patients with biochemically recurrent prostate cancer after radical prostatectomy with a positive finding within the prostate fossa or pelvic nodes on 18F-fluciclovine PET/CTs were identified from the LOCATE patient population. Areas of gross disease were delineated. Prostate fossa contours were delineated using both the 2010 RTOG consensus guidelines and the recently published 2020 GFRU consensus guidelines. Pelvic nodes were contoured with both the 2009 RTOG consensus guidelines and the 2020 NRG consensus guidelines. The performance of the contouring guidelines was assessed by determining what proportion of gross recurrent lesions were encompassed completely or marginally. Of the 213 patients within the LOCATE trial, 45 patients were eligible for analysis with positive 18F-fluciclovine PET findings. Of the 30 total prostate fossa recurrences, the 2010 RTOG contour covered 20 (67%) and missed or marginally covered 10 (33%). The 2020 GFRU contour covered 27 recurrences (90%), and missed or marginally covered 3 (10%). Of the 43 total nodal recurrences, the 2009 RTOG pelvic nodal contour covered 29 nodes (67%), and missed or marginally covered 14 (32%). The 2020 NRG pelvic nodal contour covered 43 nodes (100%), with no misses or marginal coverage. This secondary analysis of the LOCATE trial exemplifies the improved coverage of the latest prostate fossa contouring recommendations from the GFRU. Similarly, it also validates the updated 2020 NRG pelvic nodal contouring guidelines by demonstrating improved coverage of recurrent disease in this patient population.

18F-fluciclovine positron emission tomography (PET) in metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate.

TPS171 Background: Conventional imaging of prostate cancer has limitations in staging, restaging after biochemical relapse, and response assessment. Functional imaging with positron emission tomography (PET) can target various aspects of tumor biology and has shown to be superior in the detection of prostate cancer compared with conventional computed tomography (CT) and bone scans. 18F-Fluciclovine, a synthetic amino acid transported across mammalian cell membranes by amino acid transporters that is upregulated to a greater extent in prostate cancer cells than in surrounding tissue, is currently approved for PET imaging for patients with biochemical recurrence. The role of 18F-Fluciclovine PET scans in monitoring response to novel hormonal therapies such as abiraterone acetate is unclear. We hypothesize that 1) using 18F-Fluciclovine PET scanning will allow a more sensitive assessment of mCRPC patients at the initiation of systemic therapy with abiraterone acetate and 2) the changes observed in 18F-Fluciclovine PET will correlate better with the serologic changes in PSA, allowing superior disease monitoring, than conventional imaging modalities. Methods: This single-arm, pilot study (NCT04158245) will describe the changes in 18F-Fluciclovine PET scan and compare these results with PSA and conventional computerized tomography (CT) and bone scans, in mCRPC patients treated with abiraterone acetate plus prednisone. Patients must have a detectable baseline PSA of ≥ 2 ng/mL and metastatic disease detected on conventional CT and bone scans. The use of docetaxel in the hormone-sensitive setting is allowed. Twelve patients will be treated with abiraterone 1000 mg daily plus prednisone 5 mg (or dexamethasone 0.5 mg) daily for mCRPC and get 18F-Fluciclovine PET and conventional CT and bone scans at baseline and 12 weeks after starting abiraterone therapy or at disease progression. PSA progression will be defined as a repeated increase in PSA of at least 2 ng/dL and 25% from nadir values, at least 1 week apart, according to PCWG3 criteria and clinical or radiographic progression by RECIST version 1.1. The co-primary objectives of the study include the 18F-Fluciclovine PET changes at baseline and 12 weeks after abiraterone acetate for mCRPC and the comparison between 18F-Fluciclovine PET and conventional scans. Secondary and exploratory endpoints include PSA response, PSA progression and genomic alterations by next-generation sequencing. As of 12 September 2020, this trial is actively enrolling. Clinical trial information: NCT04158245.

18F-Fluciclovine Positron Emission Tomography in Prostate Cancer: A Systematic Review and Diagnostic Meta-Analysis.

Background: to explore the diagnostic accuracy of 18F-Fluciclovine positron-emission tomography (PET) in prostate cancer (PCa), considering both primary staging prior to radical therapy, biochemical recurrence, and advanced setting. Methods: A systematic web search through Embase and Medline was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies performed from 2011 to 2020 were evaluated. The terms used were “PET” or “positron emission tomography” or “positron emission tomography/computed tomography” or “PET/CT” or “positron emission tomography-computed tomography” or “PET-CT” and “Fluciclovine” or “FACBC” and “prostatic neoplasms” or “prostate cancer” or “prostate carcinoma”. Only studies reporting about true positive (TP), true negative (TN), false positive (FP) and false negative (FN) findings of 18F-fluciclovine PET were considered eligible. Results: Fifteen out of 283 studies, and 697 patients, were included in the final analysis. The pooled sensitivity for 18F-Fluciclovine PET/CT for diagnosis of primary PCa was 0.83 (95% CI: 0.80–0.86), the specificity of 0.77 (95% CI: 0.74–0.80). The pooled sensitivity for preoperative LN staging was 0.57 (95% CI: 0.39–0.73) and specificity of 0.99 (95% CI: 0.94–1.00). The pooled sensitivity for the overall detection of recurrence in relapsed patients was 0.68 (95% CI: 0.63–0.73), and specificity of 0.68 (95% CI: 0.60–0.75). Conclusion: This meta-analysis showed promising results in term of sensitivity and specificity for 18F-Fluciclovine PET/CT to stage the primary lesion and in the assessment of nodal metastases, and for the detection of PCa locations in the recurrent setting. However, the limited number of studies and the broad heterogeneity in the selected cohorts and in different investigation protocols are limitation affecting the strength of these results.

18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy

BackgroundProstate cancer is highly prevalent worldwide. Androgen deprivation therapy (ADT) remains the treatment of choice for incurable prostate cancer, but majority of patients develop disease recurrence following ADT. There is therefore an urgent need for early detection of treatment resistance.MethodsIsogenic androgen-responsive (CWR22Res) and castration-resistant (22Rv1) human prostate cancer cells were implanted into the anterior lobes of the prostate in CD-1 Nu mice to generate prostate orthografts. Castrated mice bearing CWR22Res and 22Rv1 orthografts mimic clinical prostate cancer following acute and chronic ADT, respectively. 18F-Fluciclovine (1-amino-3-fluorocyclobutane-1-carboxylic acid) with a radiochemical purity of > 99% was produced on a FASTlab synthesiser. Ki67 staining in endpoint orthografts was studied. Western blot, quantitative RT-PCR and next-generation sequencing transcriptomic analyses were performed to assess the expression levels of amino acid transporters (including LAT1 and ASCT2, which have been implicated for Fluciclovine uptake). Longitudinal metabolic imaging with 18F-Fluciclovine-based positron emission tomography (PET) was performed to study tumour response following acute and chronic ADT.ResultsBoth immunohistochemistry analysis of endpoint prostate tumours and longitudinal 18F-Fluciclovine imaging revealed tumour heterogeneity, particularly following ADT, with in vivo 18F-Fluciclovine uptake correlating to viable cancer cells in both androgen-proficient and castrated environment. Highlighting tumour subpopulation following ADT, both SUVpeak and coefficient of variation (CoV) values of 18F-Fluciclovine uptake are consistent with tumour heterogeneity revealed by immunohistochemistry. We studied the expression of amino acid transporters (AATs) for 18F-Fluciclovine, namely LAT1 (SLC7A5 and SLC3A2) and ASCT2 (SLC1A5). SLC7A5 and SLC3A2 were expressed at relatively high levels in 22Rv1 castration-resistant orthografts following chronic ADT (modelling clinical castration-resistant disease), while SLC1A5 was preferentially expression in CWR22Res tumours following acute ADT. Additional AATs such as SLC43A2 (LAT4) were shown to be upregulated following chronic ADT by transcriptomic analysis; their role in Fluciclovine uptake warrants investigation.ConclusionWe studied in vivo 18F-Fluciclovine uptake in human prostate cancer orthograft models following acute and chronic ADT. 18F-Fluciclovine uptakes highlight tumour heterogeneity that may explain castration resistance and can be exploited as a clinical biomarker.

Abstract 15754: Coronary Calcification is Associated With Prior GnRH Agonist Therapy in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Gonadotropin releasing hormone (GnRH) agonist therapy is associated with major adverse cardiovascular (CV) events in men with prostate cancer. The effect of GnRH agonists on vascular calcification is not known. Methods: Consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET) /computed tomography (CT) at our institution for recurrent prostate cancer were retrospectively identified. Clinical and demographic data were obtained from the medical record. Patients without available data on prior prostate cancer therapies received were excluded (n=25). Coronary calcification was qualitatively assessed on non-gated CT scans using a published scoring system. The association of prior GnRH agonist therapy with coronary calcification was evaluated using stratified odds ratio (OR) analysis in a 2x2 contingency table. Results: Among 186 men included, median age was 69.0 years (IQR 64.3, 74.5) and CV comorbidities were common (72% hypertension, 68% hyperlipidemia, 43% current or former smoking, and 21% diabetes mellitus). 55 patients (30%) received prior hormone therapy, 50 of whom received a GnRH agonist either as single- or multi-agent therapy. Men with prior GnRH agonists were older than those without prior GnRH agonists (71.4 vs. 68.4 years, p=0.025). There were no significant differences in prevalence of CV comorbidities between the two groups. Men with at least mild coronary calcification were more likely to have received prior GnRH agonist therapy (OR=3.0, 95% CI 1.2-7.1, p=0.015 by Fisher’s exact test), with a stronger association seen in younger men (OR=3.9, age &lt;69 years) than in older men (OR=1.8, age ≥69). Conclusions: Coronary calcification is associated with prior GnRH agonist therapy in men with recurrent prostate cancer undergoing PET/CT imaging. The utility of vascular protective therapies including aspirin and statin to mitigate the adverse CV effects of GnRH agonists requires further study.

Abstract 14548: Coronary and Aortic Calcification Are Common in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Men who receive androgen deprivation therapy for prostate cancer may be at increased risk for cardiovascular events. Vascular calcification is predictive of coronary events in the general population. The prevalence of vascular calcification in men with prostate cancer is not known. Methods: 211 consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET) /computed tomography (CT) at Washington University School of Medicine for recurrent prostate cancer were retrospectively identified. Clinical, demographic, and cardiac biomarker data were obtained from the medical record. Coronary and aortic calcification were qualitatively assessed on non-gated CT scans using standardized scoring systems. Results: Among 211 men with recurrent prostate cancer, median age was 69 (IQR 64, 75) years. Cardiovascular comorbidities were common (70% hypertension, 65% hyperlipidemia, 20% diabetes mellitus, 47% current or former smoking). 21% carried a clinical diagnosis of coronary artery disease while 6% had peripheral vascular disease. On CT imaging, 147 patients (70%) had coronary artery calcification of whom 29 (20%) had severe calcification. Additionally, 189 patients (90%) had aortic calcification on CT imaging of whom 48 (25%) had severe thoracic aortic calcification and 109 (58%) had severe calcification at the aortoiliac bifurcation. Conclusions: Coronary and peripheral vascular calcification are common on PET/CT imaging in men with prostate cancer. Vascular calcification on CT imaging may have utility for cardiovascular risk stratification and guiding implementation of cardiovascular therapies in men receiving androgen deprivation therapy.

Abstract 14602: Vascular Calcification is Associated With Major Adverse Cardiovascular Events and Mortality in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Hormone therapy is a front-line therapy for men with prostate cancer and is associated with adverse cardiovascular events. The utility of vascular calcification for cardiovascular risk stratification in men with prostate cancer is unknown. Methods: 211 consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET)/computed tomography (CT) at a single institution for recurrent prostate cancer were retrospectively identified. Clinical and demographic data were obtained from the medical record. Coronary and aortic calcification were qualitatively assessed on non-gated CT scans using standardized scoring systems. The primary outcome was a composite of subsequent major adverse cardiovascular event (MACE; myocardial infarction, stroke, coronary or peripheral revascularization, heart failure hospitalization) or all-cause mortality. Results: Median age was 69 (IQR 64, 75) years and cardiovascular comorbidities were common (70% hypertension, 65% hyperlipidemia, 47% current or former smoking, 20% diabetes mellitus). Over a median of 16.5 months, 8 patients (4%) met the primary outcome. Patients with MACE or death were older and had higher prevalence of traditional cardiovascular comorbidities (risk ratio [RR] 1.3 for hypertension, 1.4 for hyperlipidemia, 1.3 for diabetes mellitus; p&gt;0.05 for all). Coronary and aortic calcification were more common in patients with MACE or death. Severe coronary calcification (RR=6.1, 95% CI 1.6-23.2, p=0.008) and severe thoracic aortic calcification (RR=9.9, 95% CI 2.0-47.6, p=0.004) were associated with significantly increased risk of MACE or death. Conclusions: Coronary and aortic calcification on PET/CT imaging are associated with significantly increased risk of MACE or death in men with recurrent prostate cancer. Vascular calcification may have utility for cardiovascular risk stratification in men receiving hormone therapy for prostate cancer.

Synchronous Malignancies Identified by 18F-fluciclovine Positron Emission Tomography for Prostate Cancer: Case Series and Mini-Review.

Positron emission tomography using the fluorine-18 (18F) fluciclovine radiotracer has been approved for use in recurrent prostate cancer and is a useful tool for clinical decision making. However, 18F-fluciclovine is not specific for prostate cancer tumor cells, and false-positive results have been reported. In the present study, we have reported our experience with synchronous malignancies identified using 18F-fluciclovine and reviewed other reported cases, with a special emphasis on highlighting the clinical decisions that led to the correct diagnosis.

18F-Fluciclovine Positron Emission Tomography in Men With Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy and Planning to Undergo Salvage Radiation Therapy: Results from LOCATE

PurposeConventional imaging rarely localizes the site(s) of prostate cancer recurrence in patients undergoing evaluation for salvage radiation therapy (sRT) after radical prostatectomy (RP). LOCATE (NCT02680041) was a prospective, multicenter study investigating the impact of 18F-fluciclovine positron emission tomography and computed tomography (PET/CT) on the management of patients with biochemical recurrence of prostate cancer after curative-intent radiation or RP and negative or equivocal conventional imaging. Our objective was to determine the impact of 18F-fluciclovine PET/CT on treatment decisions for men planning to undergo sRT for biochemical recurrence post-RP. Methods and MaterialsWe conducted a subgroup analysis of post-RP patients enrolled in LOCATE who were planning to undergo sRT with or without hormonal therapy based on prescan documentation. 18F-Fluciclovine PET/CT was performed according to standardized procedures. The treatment plan postscan was compared with the prescan plan, and Fisher exact test was used to determine the impact of prescan prostate-specific antigen (PSA) and Gleason sum (GS) on positivity and anatomic patterns of uptake. ResultsA total of 114 patients (median prescan PSA 0.42 [interquartile range, 0.3-1.1] ng/mL) met selection criteria (54% of patients in LOCATE). Forty-eight (42%) had 18F-fluciclovine-avid lesions. Twelve patients (11%) had positive findings only in the prostate bed, 24 (21%) had positivity only in the pelvis (prostate bed or pelvic nodes), and 24 (21%) had extrapelvic findings. PSA >0.5 ng/mL and GS ≥8 were associated with a higher risk of extrapelvic positivity (P < .05).Postscan, 55 (48%) patients had a management change; 37 (32%) had a change in overall treatment approach (ie, omission of sRT); and 18 (16%) had sRT target modification. Conclusions18F-Fluciclovine PET/CT is positive in nearly half of patients planning to undergo post-RP sRT with negative/equivocal conventional imaging, with findings frequently leading to changes in management. PSA >0.5 ng/mL and GS ≥8 are associated with a higher risk of extrapelvic positive findings.

Effect of 18F-Fluciclovine Positron Emission Tomography on the Management of Patients With Recurrence of Prostate Cancer: Results From the FALCON Trial

Early and accurate localization of lesions in patients with biochemical recurrence (BCR) of prostate cancer may guide salvage therapy decisions. The present study, 18F-Fluciclovine PET/CT in biochemicAL reCurrence Of Prostate caNcer (FALCON; NCT02578940), aimed to evaluate the effect of 18F-fluciclovine on management of men with BCR of prostate cancer. Men with a first episode of BCR after curative-intent primary therapy were enrolled at 6 UK sites. Patients underwent 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) according to standardized procedures. Clinicians documented management plans before and after scanning, recording changes to treatment modality as major and changes within a modality as other. The primary outcome measure was record of a revised management plan postscan. Secondary endpoints were evaluation of optimal prostate specific antigen (PSA) threshold for detection, salvage treatment outcome assessment based on 18F-fluciclovine-involvement, and safety. 18F-Fluciclovine was well tolerated in the 104 scanned patients (median PSA = 0.79 ng/mL). Lesions were detected in 58 out of 104 (56%) patients. Detection was broadly proportional to PSA level; ≤1 ng/mL, 1 out of 3 of scans were positive, and 93% scans were positive at PSA >2.0 ng/mL. Sixty-six (64%) patients had a postscan management change (80% after a positive result). Major changes (43 out of 66; 65%) were salvage or systemic therapy to watchful waiting (16 out of 66; 24%); salvage therapy to systemic therapy (16 out of 66; 24%); and alternative changes to treatment modality (11 out of 66, 17%). The remaining 23 out of 66 (35%) management changes were modifications of the prescan plan: most (22 out of 66; 33%) were adjustments to planned brachytherapy/radiation therapy to include a 18F-fluciclovine-guided boost. Where 18F-fluciclovine guided salvage therapy, the PSA response rate was higher than when 18F-fluciclovine was not involved (15 out of 17 [88%] vs 28 out of 39 [72%]). 18F-Fluciclovine PET/CT located recurrence in the majority of men with BCR, frequently resulting in major management plan changes. Incorporating 18F-fluciclovine PET/CT into treatment planning may optimize targeting of recurrence sites and avoid futile salvage therapy.

18F-fluciclovine PET or PSMA PET for prostate cancer imaging?

Data from a new study suggests that prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging is superior to 18F-fluciclovine PET for detecting biochemical recurrence in men with prostate cancer. However, whether one of these radiotracers improves patient survival over the other is unknown and further research is needed to determine which has the greater effect.

Diagnostic Value and Reproducibility of Positron Emission Tomography with 18f-Fluciclovine in High- and Low-Grade Glioma

Positron emission tomography (PET) with amino acid analogs is a useful tool in the diagnostics and therapy planning of gliomas. PET-based delineation of the tumor volume enables delivery of a more targeted radiation dose and sparing of normal brain tissue, with potential consequences for patient survival. PET tracer, 18F-fluciclovine, has Orphan Drug designation in the US and Europe for imaging gliomas. Here, we explored its diagnostic performance and reproducibility in high- and low-grade gliomas when interpreted in combination with contrast-enhanced T1-weighted MRI (hereafter referred to as “18F-fluciclovine + CE-T1W”). In a previous prospective study, 18F-fluciclovine PET and MRI (CE-T1W and fluid-attenuated inversion recovery [FLAIR]) were performed in patients with suspected gliomas (Anaplastic astrocytoma (7), Anaplastic oligodendroglioma (1), Diffuse astrocytoma (7), Glioblastoma (14), Oligoastrocytoma (2), Oligodendroglioma (3), other: Anaplastic ependymoma (1)) Imaging data from thirty five individuals with a histopathologically confirmed diagnosis of glioma were analyzed. A neuroradiologist read the MRI images, while three blinded, 18F-fluciclovine-naïve, experienced nuclear medicine physicians interpreted 18F-fluciclovine + CE-T1W. Diagnostic performance was determined for CE-T1W, FLAIR and 18F-fluciclovine + CE-T1W. Inter- and intra-reader reproducibility (via a re-read of a random 20% of images) were assessed using Cohen’s kappa and Fleiss’ kappa statistics. Results were stratified by tumor grade, i.e. high and low. Across the three readers, the positive predictive value (PPV) for 18F-fluciclovine + CE-T1W was 96%, the negative predictive value (NPV) was 38-42%, the sensitivity was 66−71%, and specificity was 89%. For high-grade tumors (n = 15), the PPV, NPV, sensitivity and specificity for 18F-fluciclovine + CE-T1W for the three readers overall were 100.0%, 40.0%, 83.3% and 100.0%, respectively. In low-grade tumors (n = 11), these were 100.0%, 45.5%, 50.0% and 100.0%, respectively. The biopsy samples for the remainder (n=9) demonstrated malignancy but the neuro-pathologist could not confidently assign a grade. Inter-reader concordance was 89% (Fleiss’ Kappa = 0.86) overall, 100% (Fleiss’ Kappa=1.00) for high-grade, and 82.4% (Fleiss’ Kappa = 0.74) for low-grade gliomas. All pair-wise inter-reader comparisons showed 100% agreement (Cohen’s Kappa = 1.0) for high-grade gliomas and ranged from 82.4−94.1% (Cohen’s Kappa = 0.6−0.87) for low-grade. Intra-reader concordance was 83.3−100% (Cohen’s Kappa =0.66−1.00) with no discernible differences when stratifying by high- or low-grade gliomas. 18F-Fluciclovine PET + CE-T1W MRI show reproducible results and good diagnostic performance for imaging gliomas, a prerequisite for accurate PET-guided radiotherapy planning.

The role of 18F-fluciclovine PET in the management of prostate cancer: a systematic review and meta-analysis

To investigate the diagnostic performance of 18F-fluciclovine positron-emission tomography (PET) or combined PET and computed tomography (PET/CT) for diagnosis of primary cancer, preoperative lymph node (LN) staging, and detection of recurrent disease of prostate cancer (PCa) through a systematic review and meta-analysis. The PubMed and EMBASE databases were searched from the earliest available date of indexing through 31 December 2018, for studies evaluating the diagnostic performance of 18F-fluciclovine PET or PET/CT for the management of PCa patients. The sensitivities, specificities, and positive and negative likelihood ratios (LR+ and LR-) across the studies were calculated and summary receiver operating characteristic curves were constructed. Across 13 studies (563 patients), the pooled sensitivity for 18F-fluciclovine PET or PET/CT for diagnosis of primary PCa was 0.87 (95% confidence interval [CI]: 0.77-0.93) and a pooled specificity of 0.84 (95% CI: 0.68-0.93). For LN staging, the pooled sensitivity was 0.56 (95% CI: 0.37-0.74) and a pooled specificity of 0.98 (95% CI: 0.88-1.00). For detection of recurrent disease, the pooled sensitivity was 0.79 (95% CI: 0.60-0.91) and a pooled specificity of 0.69 (95% CI: 0.59-0.77). In meta-regression analysis, no definite variable was the source of the study heterogeneity. The current meta-analysis showed the moderate sensitivity and specificity of 18F-fluciclovine PET or PET/CT for the diagnosis of primary cancer, preoperative LN staging, and detection of recurrent PCa. Further large multicentre studies will be necessary to substantiate the diagnostic accuracy of 18F-fluciclovine PET/CT for management of PCa patients.

Simultaneous 18F-fluciclovine Positron Emission Tomography and Magnetic Resonance Spectroscopic Imaging of Prostate Cancer.

Purpose: To investigate the associations of metabolite levels derived from magnetic resonance spectroscopic imaging (MRSI) and 18F-fluciclovine positron emission tomography (PET) with prostate tissue characteristics.Methods: In a cohort of 19 high-risk prostate cancer patients that underwent simultaneous PET/MRI, we evaluated the diagnostic performance of MRSI and PET for discrimination of aggressive cancer lesions from healthy tissue and benign lesions. Data analysis comprised calculations of correlations of mean standardized uptake values (SUVmean), maximum SUV (SUVmax), and the MRSI-derived ratio of (total choline + spermine + creatine) to citrate (CSC/C). Whole-mount histopathology was used as gold standard.Results: The results showed a moderate significant correlation between both SUVmean and SUVmax with CSC/C ratio.Conclusions: We demonstrated that the simultaneous acquisition of 18F-fluciclovine PET and MRSI with an integrated PET/MRI system is feasible and a combination of these imaging modalities has potential to improve the diagnostic sensitivity and specificity of prostate cancer lesions.

The Impact of 18F-Fluciclovine Positron Emission Tomography on Salvage Radiation Therapy Decisions for Patients with Post-Radical Prostatectomy Recurrence of Prostate Cancer: Results from LOCATE

The Impact of 18F-Fluciclovine Positron Emission Tomography on Salvage Radiation Therapy Decisions for Patients with Post-Radical Prostatectomy Recurrence of Prostate Cancer: Results from LOCATE

Fluciclovine positron emission tomography in the setting of biochemical recurrence following local therapy of prostate cancer.

Approximately one in five men will demonstrate biochemical recurrence (BCR) following local therapy for prostate cancer (PCa). Advanced imaging modalities including positron emission tomography (PET) imaging of various radiotracers have become more commonplace to visualize foci of disease recurrence. We performed a systematic review of the literature to describe current evidence in support of 18F-fluciclovine (Axumin) PET imaging in this clinical setting. An English literature search was conducted on PubMed/Medline for original investigations on 18F-fluciclovine PET for PCa. Boolean criteria included the terms: prostate, fluciclovine, FACBC and Axumin. Published articles meeting these criteria and their respective bibliographies and diagnostic modalities were included after review, when appropriate. Our literature review identified 93 articles. Among these, 18 met our inclusion criteria. Evidence suggests 18F-fluciclovine PET imaging is safe, well-tolerated and offers acceptable sensitivity and specificity for the detection of localized intraglandular and extraprostatic PCa foci in the setting of persistence or recurrence after primary treatment. Compared to other available PET radiotracers available, evidence suggests that 18F-fluciclovine may outperform ProstaScint and 11C-choline in this clinical setting. Furthermore, 18F-fluciclovine PET may aid guiding decision-making in regards to salvage therapy planning. Further investigation is warranted to validate these early findings and to further compare this agent to other available radiotracers in this setting.

Comparison of time curves from dynamic 18F-fluciclovine positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging for primary prostate carcinomas.

Multimodal imaging is increasingly included in the assessment of prostate cancer patients, and there is a need to study whether different techniques provide similar or complementary information. In the initial perfusion phase contrast agents and radioactive labelled tracers act as blood-pool agents and may show similar characteristics. The purpose of the current work was to compare time-activity- and time-concentration-curves (TCs) of dynamic 18F-fluciclovine (18F-anti-1-amino-2-[F]-fluorocyclobutane-1-carboxylic acid, FACBC) positron emission tomography (PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Dynamic FACBC PET and DCE MRI were performed on 22 patients with intermediate or high-risk prostate cancer within 23 days prior to robot-assisted laparoscopic prostatectomy. Index tumour was delineated in the images using whole mount tissue sections as reference standard. Tumour TCs from PET and MRI were compared visually and quantitatively by calculating correlation coefficients between the curves at different time points after injection. For the first minute post injection, the mean correlation coefficient between the TCs from PET and MRI was 0.92 (range; 0.75-0.99). After the first minute, MRI showed washout while PET showed plateau kinetics. Dynamic FACBC and DCE MRI showed similar wash-in time curve characteristics. At later time points, FACBC plateaued whereas MR contrast medium washed out. In DCE MRI, the usefulness of wash-in information is well documented. Whether wash-in information from dynamic FACBC can provide added value remains to be documented.