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).

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.

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.

Initial Experience with the Radiotracer 18F-Fluciclovine PET/CT in Ovarian Cancer.

OBJECTIVE: Early and accurate staging of ovarian cancer is paramount to disease survival. Conventional imaging including FDG PET/CT are limited in the evaluation of small metastatic lesions. 18F-Fluciclovine has minimal urine and bowel excretion allowing optimal visualization of the abdomen and pelvis. This study examines 18F-fluciclovine uptake in known primary and recurrent ovarian cancer. METHODS: Seven patients with a confirmed diagnosis of epithelial ovarian cancer underwent 18F-fluciclovine PET/CT imaging. Forty-one (41) lesions were identified with 18F-fluciclovine and confirmed to be true positive (n = 41). We aim to explore if 18F-fluciclovine uptake in ovarian lesions were greater than background uptake of bone marrow, blood pool, and bladder. Quantification analysis was performed to determine max and mean standard uptake values (SUVmax and SUVmean) of known and suspected lesions compared to SUVmean uptake of background structures. RESULTS: 18F-Fluciclovine demonstrated 100% sensitivity (41/41) for uptake in known ovarian lesions. The average SUVmax (±SD) uptake of known ovarian lesions was 5.9 (±2.6) and 5.1 (±2.0) on early and delayed images, respectively. The average tumor SUVmax to SUVmean of background (±SD) (T:B) ratios on early and delay were 1.9 (±0.8), 2.1 (±0.9) for marrow; 3.8 (±1.8), 3.4 (±1.5) for aorta; and 8.4 (±4.3), 1.5 (±1.7) for bladder, respectively. CONCLUSION: 18F-Fluciclovine uptake in malignant ovarian lesions was above background levels suggesting its feasibility in the imaging of ovarian cancer. Due to increasing tracer washout via the urinary bladder over time, early imaging at 4 min post injection is favorable.

Prostate Cancer Skeletal Metastasis: A Spontaneous Evolution from Osteolytic to Osteoblastic Morphology without Treatment.

Skeletal metastases due to prostate cancer (PCa) are more commonly osteoblastic than osteolytic. In the rarer cases of osteolytic skeletal metastasis of PCa, transition to osteoblastic phenotype occurs following treatment, which indicates successful healing. In this report, we present a case of spontaneous osteolytic to osteoblastic evolution of PCa skeletal metastasis without treatment in a patient with recurrence of PCa. Our patient is a 59-year-old male who had a robotic radical prostatectomy in July 2014 for a T2c adenocarcinoma of the prostate gland (Gleason score = 4 + 3). He had adjuvant pelvic radiotherapy in January 2015 due to prostate-specific antigen (PSA) persistence. PSA began to rise in October 2015. An 18 F-fluciclovine positron emission tomography/computed tomography (PET/CT) scan obtained in June 2017 at a PSA of 0.5 ng/mL was negative. Repeat 18 F-fluciclovine PET/CT of February 2020 at PSA of 3.72 ng/mL showed prostate bed recurrence and a nonavid osteolytic left inferior pubic ramus lesion. 18F radiohybrid prostate-specific membrane antigen ( 18 F-rhPSMA) PET/CT scan of August 2020 performed as part of an ongoing clinical trial confirmed local prostate bed recurrence with a low-grade radiotracer uptake in the osteolytic left inferior pubic ramus bone lesion. Without salvage therapy, 18 F-fluciclovine PET/CT of October 2020 and March 2022 shows progressive sclerosis in the left pubic ramus lesion. An osteolytic to osteoblastic transition of a bone lesion as shown in this patient calls for a rethink in our understanding of untreated PCa skeletal metastasis progression. This case provides novel insight into the understanding of the temporal evolution of skeletal metastasis and calls for further research.

Diagnostic Accuracy of PET with 18F-Fluciclovine ([18F]FACBC) in Detecting High-Grade Gliomas: A Systematic Review and Meta-Analysis.

BACKGROUND: 18F-Fluciclovine ([18F]FACBC) has been recently proposed as a synthetic radiolabeled amino acid for positron emission tomography (PET) imaging in patients with brain neoplasms. Our aim is to evaluate the diagnostic performance of [18F]FACBC PET in high-grade glioma (HGG) patients, taking into account the literature data. METHODS: A comprehensive literature search was performed. We included original articles evaluating [18F]FACBC PET in the detection of HGG before therapy and for the suspicion of tumor recurrence. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratios (DOR), including 95% confidence intervals (95% CI), were measured. Statistical heterogeneity and publication bias were also assessed. RESULTS: ten studies were included in the review and eight in the meta-analysis (113 patients). Regarding the identification of HGG, the sensitivity of [18F]FACBC PET ranged between 85.7% and 100%, with a pooled estimate of 92.9% (95% CI: 84.4-96.9%), while the specificity ranged from 50% to 100%, with a pooled estimate of 70.7% (95% CI: 47.5-86.5%). The pooled LR+, LR-, and DOR of [18F]FACBC PET were 2.5, 0.14, and 37, respectively. No significant statistical heterogeneity or publication bias were found. CONCLUSIONS: evidence-based data demonstrate the good diagnostic accuracy of [18F]FACBC PET for HGG detection. Due to the still limited data, further studies are warranted to confirm the promising role of [18F]FACBC PET in this context.

18F-Fluciclovine Uptake in an Incidentally Discovered Meningioma in a Patient With a History of Metastatic Prostate Cancer: A Case Report.

Meningiomas are common, benign tumors found in the dural layers of the central nervous system (CNS) that are often found incidentally. 18F-fluciclovine is an amino acid radiotracer that is used to monitor the recurrence of prostate cancer due to its high uptake in prostate cancer cells. This case report outlines a patient with a retinoblastoma tumor suppressor gene (RB1) mutation and prostate cancer metastasis to the bone incidentally noted to have an enhancing, extra-axial mass on a screening MRI. On prior scans, the mass displayed increased 18F-fluciclovine uptake. Because prostate cancer can metastasize to the meninges, especially in older patients with advanced disease, consideration was given to the progression of his oncological disease. However, additional imaging validated the existence and size of the mass, making a meningioma the final diagnosis. Meningeal metastases can be virtually indistinguishable from other CNS tumors, including meningiomas appearing as single or multiple dural-based, enhancing masses, and without prior imaging, further investigation is warranted.

Other Novel PET Radiotracers for Breast Cancer.

Many novel PET radiotracers have demonstrated potential use in breast cancer. Although not currently approved for clinical use in the breast cancer population, these innovative imaging agents may one day play a role in the diagnosis, staging, management, and even treatment of breast cancer.

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.

ACR Appropriateness Criteria® Post-Treatment Follow-up of Prostate Cancer: 2022 Update.

Prostate cancer has a wide spectrum ranging between low-grade localized disease and castrate-resistant metastatic disease. Although whole gland and systematic therapies result in cure in the majority of patients, recurrent and metastatic prostate cancer can still occur. Imaging approaches including anatomic, functional, and molecular modalities are continuously expanding. Currently, recurrent and metastatic prostate cancer is grouped in three major categories: 1) Clinical concern for residual or recurrent disease after radical prostatectomy, 2) Clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments, and 3) Metastatic prostate cancer treated by systemic therapy (androgen deprivation therapy, chemotherapy, immunotherapy). This document is a review of the current literature regarding imaging in these settings and the resulting recommendations for imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Amino Acid PET in Neurooncology.

For decades, several amino acid PET tracers have been used to optimize diagnostics in patients with brain tumors. In clinical routine, the most important clinical indications for amino acid PET in brain tumor patients are differentiation of neoplasm from nonneoplastic etiologies, delineation of tumor extent for further diagnostic and treatment planning (i.e., diagnostic biopsy, resection, or radiotherapy), differentiation of treatment-related changes such as pseudoprogression or radiation necrosis after radiation or chemoradiation from tumor progression at follow-up, and assessment of response to anticancer therapy, including prediction of patient outcome. This continuing education article addresses the diagnostic value of amino acid PET for patients with either glioblastoma or metastatic brain cancer.

Impact of 18F-fluciclovine PET/CT on plans for androgen deprivation therapy in patients with biochemical recurrence of prostate cancer: data analysis from two prospective clinical trials.

INTRODUCTION: Despite early detection and primary therapy improvements, biochemical recurrence (BCR) of prostate cancer remains common. The advent of highly sensitive molecular imaging has facilitated identification of men with limited metastatic disease burden that might be more optimally treated with metastases-directed therapy than with androgen deprivation therapy (ADT). The LOCATE (NCT02680041) and FALCON (NCT02578940) trials assessed the impact of 18F-fluciclovine PET/CT on the management of patients with BCR after curative-intent primary therapy. We performed a secondary analysis of LOCATE and FALCON data to characterize sites of recurrence and management decisions for BCR patients who had an intended management plan including ADT prior to undergoing 18F-fluciclovine PET/CT. METHODS: Data from 317 LOCATE/FALCON patients who underwent 18F-fluciclovine PET/CT were analyzed and those with a prescan plan for ADT (± another treatment) were selected. 18F-Fluciclovine detection rates were determined at the patient level and for the prostate/prostate bed region, pelvic and extra-pelvic lymph nodes (LN), soft tissues, and bones. The patients' pre- and postscan treatment plans were compared and were stratified by imaging results. RESULTS: A total of 146 patients had a prescan plan for ADT (60 as monotherapy and 86 in combination with another modality). 18F-Fluciclovine detected lesions in 85 of 146 (58%) patients planned for ADT. Detection rates in the prostate/bed, pelvic LN, extra-pelvic LN, soft tissues and bone were 30%, 25%, 13%, 2.1%, and 13%, respectively. Twenty-five (17%) patients had positivity confined to the prostate/bed, 21 (14%) had 18F-fluciclovine-positive pelvic LN (±prostate/bed) but no other involvement and 39 (27%) had involvement outside the prostate/bed and pelvic LN. Postscan, 93 of 146 (64%) patients had a management change, 55 (59%) of which were to abort ADT. Only 25% of the patients originally planned for ADT monotherapy still had an unaltered plan for ADT monotherapy postscan. Patients with a postscan plan for ADT monotherapy had the most disseminated disease. Disease in the prostate/bed only was most common in those whose plan was altered to abort ADT. CONCLUSIONS: 18F-Fluciclovine-PET/CT influenced management plans for the majority of patients with a prescan plan for ADT. Plans were commonly amended to target salvage therapy for lesions identified with 18F-fluciclovine PET/CT, and consequently likely spared/delayed patients the morbidity associated with ADT.

Distinguishing Progression from Pseudoprogression in Glioblastoma Using 18F-Fluciclovine PET.

Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. 18F-fluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of 18F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative 18F-fluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP (≥50% viable tumor), mixed TP (<50% and >10% viable tumor), or pseudoprogression (≤10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40- to 50-min SUVmax (6.64 + 1.88 vs. 4.11 ± 1.52, P = 0.009) than patients with pseudoprogression. A 40- to 50-min SUVmax cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40- to 50-min SUVmax cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: 18F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of 18F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with 18F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.

Differences in Failure-Free Survival After Salvage Radiotherapy Guided by Conventional Imaging Versus 18F-Fluciclovine PET/CT in Postprostatectomy Patients: A Post Hoc Substratification Analysis of the EMPIRE-1 Trial.

The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement 1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by 18F-fluciclovine PET/CT versus conventional imaging. We performed a post hoc analysis of the EMPIRE-1 cohort stratified by protocol-specified criteria, comparing failure-free survival (FFS) between study arms. Methods: EMPIRE-1 randomized patients to SRT planning via either conventional imaging only (bone scanning plus abdominopelvic CT or MRI) (arm A) or conventional imaging plus 18F-fluciclovine PET/CT (arm B). Randomization was stratified by prostate-specific antigen (PSA) level (<2.0 vs. ≥ 2.0 ng/mL), adverse pathology, and androgen-deprivation therapy (ADT) intent. We subdivided patients in each arm using the randomization stratification criteria and compared FFS between patient subgroups across study arms. Results: Eighty-one and 76 patients received per-protocol SRT in study arms A and B, respectively. The median follow-up was 3.5 y (95% CI, 3.0-4.0). FFS was 63.0% and 51.2% at 36 and 48 mo, respectively, in arm A and 75.5% at both 36 and 48 mo in arm B. Among patients with a PSA of less than 2 ng/mL (mean, 0.42 ± 0.42 ng/mL), significantly higher FFS was seen in arm B than arm A at 36 mo (83.2% [95% CI, 70.0-91.0] vs. 66.5% [95% CI, 51.6-77.8], P < 0.001) and 48 mo (83.2% [95% CI, 70.0-91.0] vs. 56.2% [95% CI, 40.5-69.2], P < 0.001). No significant difference in FFS between study arms in patients with a PSA of at least 2 ng/mL was observed. Among patients with adverse pathology, significantly higher FFS was seen in arm B than arm A at 48 mo (68.9% [95% CI, 52.1-80.8] vs. 42.8% [95% CI, 26.2-58.3], P < 0.001) though not at the 36-mo follow-up. FFS was higher in patients without adverse pathology in arm B versus arm A (90.2% [95% CI, 65.9-97.5] vs. 73.1% [95% CI, 42.9-89.0], P = 0.006) at both 36 and 48 mo. Patients in whom ADT was intended in arm B had higher FFS than those in arm A, with the difference reaching statistical significance at 48 mo (65.2% [95% CI, 40.3-81.7] vs. 29.1 [95% CI, 6.5-57.2], P < 0.001). Patients without ADT intent in arm B had significantly higher FFS than patients in arm A at 36 mo (80.7% [95% CI, 64.9-90.0] vs. 68.0% [95% CI, 51.1-80.2]) and 48 mo (80.7% [95% CI, 64.9-90.0] vs. 58.6% [95% CI, 41.0-72.6]). Conclusion: The survival advantage due to the addition of 18F-fluciclovine PET/CT to SRT planning is maintained regardless of the presence of adverse pathology or ADT intent. Including 18F-fluciclovine PET/CT to SRT leads to survival benefits in patients with a PSA of less than 2 ng/mL but not in patients with a PSA of 2 ng/mL or higher.

18F-Fluciclovine PET Imaging of Glutaminase Inhibition in Breast Cancer Models.

Aggressive cancers such as triple-negative breast cancer (TNBC) avidly metabolize glutamine as a feature of their malignant phenotype. The conversion of glutamine to glutamate by the glutaminase enzyme represents the first and rate-limiting step of this pathway and a target for drug development. Indeed, a novel glutaminase inhibitor (GLSi) has been developed and tested in clinical trials but with limited success, suggesting the potential for a biomarker to select patients who could benefit from this novel therapy. Here, we studied a nonmetabolized amino acid analog, 18F-fluciclovine, as a PET imaging biomarker for detecting the pharmacodynamic response to GLSi. Methods: Uptake of 18F-fluciclovine into human breast cancer cells was studied in the presence and absence of inhibitors of glutamine transporters and GLSi. To allow 18F-fluciclovine PET to be performed on mice, citrate in the tracer formulation is replaced by phosphate-buffered saline. Mice bearing triple-negative breast cancer (TNBC) xenografts (HCC38, HCC1806, and MBA-MD-231) and estrogen receptor-positive breast cancer xenografts (MCF-7) were imaged with dynamic PET at baseline and after a 2-d treatment of GLSi (CB839) or vehicle. Kinetic analysis suggested reversible uptake of the tracer, and the distribution volume (VD) of 18F-fluciclovine was estimated by Logan plot analysis. Results: Our data showed that cellular uptake of 18F-fluciclovine is mediated by glutamine transporters. A significant increase in VD was observed after CB839 treatment in TNBC models exhibiting high glutaminase activity (HCC38 and HCC1806) but not in TNBC or MCF-7 exhibiting low glutaminase. Changes in VD were corroborated with changes in GLS activity measured in tumors treated with CB839 versus vehicle, as well as with changes in VD of 18F-(2S,R4)-fluoroglutamine, which we previously validated as a measure of cellular glutamine pool size. A moderate, albeit significant, decrease in 18F-FDG PET signal was observed in HCC1806 tumors after CB839 treatment. Conclusion: 18F-fluciclovine PET has potential to serve as a clinically translatable pharmacodynamic biomarker of GLSi.

F-18 Fluciclovine PET-CT Findings and Pseudoprogression on Immunotherapy.

Immunotherapy plays a vital role in the treatment of several types of malignancies. While the molecular targets of immunotherapy differ, the desired goal is to increase the host immune response against neoplastic tissue. This upregulated immune state results in infiltration of the tumor with activated immune cells and may be misinterpreted as disease progression in anatomical and metabolic imaging studies, known as pseudoprogression. We present a case of pseudoprogression demonstrated on a fluoride-18 (F-18) fluciclovine positron emission tomography-computed tomography (PET-CT) scan of an 85-year-old male with metastatic castrate-resistant prostate cancer who underwent treatment with sipuleucel-T. An understanding of the pseudoprogression phenomenon and its manifestations is critical for both treating physicians and imaging specialists to facilitate decision-making regarding treatment.

[18F]fluciclovine vs. [18F]fluorocholine Positron Emission Tomography/Computed Tomography: A Head-to-Head Comparison for Early Detection of Biochemical Recurrence in Prostate Cancer Patients.

Nowadays, there is still no consensus on the most accurate PET radiopharmaceutical to early detect prostate cancer (PCa) relapse. A tailored radiotracer choice based on a specific patient's profile could ensure prompt disease detection and an improvement in patients management. We aimed to compare the [18F]fluciclovine and [18F]fluorocholine PET/CT detection rate (DR) in PCa patients restaged for early biochemical recurrence (BCR), according to clinical and biochemical features. A cohort of 138 PCa patients with early BCR (mean age: 71 y, range: 50-87 y) were homogeneously randomized 1:1 to a [18F]fluciclovine or a [18F]fluorocholine PET/CT group. The respective PET/CT DR, according to per-patient and per-region analysis, and the impact of the biochemical, clinical, and histological parameters, were compared. The PSA cut-off values predictive of a positive scan were also calculated. Overall, the [18F]fluciclovine PET/CT DR was 64%, significantly higher than the [18F]fluorocholine PET/CT DR of 35% (p = 0.001). Similarly, in the per-region analysis, the [18F]fluciclovine PET/CT DR was 51% in the prostate region, significantly higher compared to 15% of [18F]fluorocholine (p < 0.0001). Furthermore, a statistically significant higher DR in per-patient and per-region (prostate/prostate bed) analysis was observed in the [18F]fluciclovine group for 0.5-1 ng/mL (p = 0.018, p = 0.049) and >1 ng/mL (p = 0.040, p < 0.0001) PSA values. A PSA of 0.45 ng/mL for [18F]fluciclovine and of 0.94 ng/mL for [18F]fluorocholine was identified as the optimal cut-off value in predicting a positive PET/CT scan. Our results demonstrated a better [18F]fluciclovine PET/CT DR compared to [18F]fluorocholine for restaging PCa patients in early BCR, particularly in the detection of locoregional recurrence. The significantly higher [18F]fluciclovine DR for low PSA values (PSA < 1 ng/mL) supports its use in this setting of patients.

Prostate Cancer Imaging with 18F-Fluciclovine.

18F-Fluciclovine PET is approved for the evaluation of patients with suspected prostate cancer recurrence. 18F-Fluciclovine PET is highly specific for the localization of extraprostatic disease even with negative conventional images and low prostate-specific antigen and has been reported to influence patients' management and improve outcome. With the recent Food and Drug Administration approval of prostate-specific membrane antigen (PSMA) PET, 18F-Fluciclovine is likely to be used as an adjunct modality in patients with suspected occult local recurrence and/or negative PSMA findings.

Digital PET/CT with 18F-FACBC in early castration-resistant prostate cancer: our preliminary results.

BACKGROUND: We assessed the role of digital PET/CT (dPET/CT) with 18F-FACBC in patients affected by castration-resistant prostate cancer with PSA levels ≤ 3 ng/mL (early CRPC), no lesions detectable at cross-sectional imaging (CIM) and bone scan (BS). METHODS: Clinical data of patients submitted to 18F-FACBC dPET/CT were retrospectively reviewed. PET/CT results were analyzed: lesions' number, location, and, in case of positive lymph nodes, largest node's short axis (i.e. SA) were annotated. According to PET/CT's results, patients with 18F-FACBC-avid lesions were further stratified into 1) unifocal; 2) oligometastatic (≤ 5 lesions); 3) disseminated (> 6 lesions). RESULTS: Twenty-four patients were enrolled. 18F-FACBC dPET/CT was positive in 21 out of 24 patients (87.5%). Thirteen patients (54.1%) showed recurrence in pelvic region, seven of whom with pelvic nodes' involvement, while eight cases (33.3%) presented 18F-FACBC-avid metastases to extra-pelvic nodes or bone. Average SA of PET-positive nodes resulted in 8.9 ± 3 mm. Patients were categorized as unifocal in four cases (26.6%), oligometastatic in 10 subjects (66.6%) and disseminated in 1 case (0.6%). PET/CT impacted on clinical management in 14 cases (58.3%). CONCLUSIONS: 18F-FACBC dPET/CT detected M1 status in 33.3% of early CRPC patients, significantly impacting on clinical management.

A Prospective Pilot Study Investigating Performance of 18F-Fluciclovine PET Imaging for Detection of Prostate Cancer 2 Years Following Primary Partial Gland Cryoablation.

Purpose: The goal of partial gland ablation (PGA) is to eradicate focal lesions of clinically significant prostate cancer (csPCa) with minimal adverse impact on functional outcomes. The primary objective of this study is to characterize the performance of 18F-Fluciclovine PET imaging for detection of prostate cancer following PGA. Materials and Methods: Subjects 2 years following primary partial gland cryoablation (PPGCA) were invited to participate in an IRB-approved study providing they met the following inclusion criteria: a single reported mpMRI region of interest (ROI) concordant with biopsy Gleason Grade Group (GGG) < 4, no gross extra-prostatic extension on mpMRI, and no GGG > 1 or GGG 1 with a core length > 6 mm on contralateral systematic biopsy. 18F-Fluciclovine PET MRI imaging of the prostate was performed followed by in and out-of-field biopsies. Results: Twenty-seven men who met eligibility criteria participated in the prospective study. In-field and out-of-field csPCa recurrence rate was 7.4% and 22.2%, respectively. The sensitivity and positive predictive value of mpMRI and PET imaging did not reach performance to reliably inform who should undergo prostate biopsy. Conclusion: At 2 years following PPGCA, the rate of in-field csPCa was exceedingly low indicating a limited role for imaging to inform in-field biopsy decisions. The csPCa detection rate of out-of-field recurrence was 22% which provides an opportunity for imaging to inform out-of-field biopsy decisions. Based on our findings, 18F-Fluciclovine PET MRI cannot be used to inform who should undergo out-of-field prostate biopsy at 2 years following PPGCA.