82Rubidium chloride positron emission tomography discrimination of recurrent intracranial malignancy from radiation necrosis.

BACKGROUND: Accurate identification and discrimination of post treatment changes from recurrent disease remains a challenge for patients with intracranial malignancies despite advances in molecular and magnetic resonance imaging. We have explored the ability of readily available Rubidium-82 chloride (82RbCl) positron emission tomography (PET) to identify and distinguish progressive intracranial disease from radiation necrosis in patients previously treated with radiation therapy. METHODS: Six patients with a total of 9 lesions of either primary (N.=3) or metastatic (N.=6) intracranial malignancies previously treated with stereotactic radiation surgery (SRS) and persistent contrast enhancement on MRI underwent brain 82RbCl PET imaging. Two patients with arteriovenous malformations previously treated with SRS, also had brain 82RbCl PET imaging for a total of 11 lesions studied. Histological confirmation via stereotactic biopsy/excisional resection was obtained for 9 lesions with the remaining 2 classified as either recurrent tumor or radiation necrosis based on subsequent MRI examinations. 82RbCl PET time activity curve analysis was performed which comprised lesion SUVmax, contralateral normal brain SUVmax, and tumor to background ratios (TBmax). RESULTS: 82RbCl demonstrates uptake greater than normal brain parenchyma in all lesions studied. Time activity curves demonstrated progressive uptake of 82RbCl in all lesions without evidence of washout. While recurrent disease demonstrated a greater mean SUVmax compared to radiation necrosis, no statistically significant difference between lesion SUVmax nor TBmax was found (P>0.05). CONCLUSIONS: 82RbCl PET produces high-contrast uptake of both recurrent disease and radiation necrosis compared to normal brain. However, no statistically significant difference was found between recurrent tumor and radiation necrosis.

Salvage Radiotherapy Management Decisions in Postprostatectomy Patients with Recurrent Prostate Cancer Based on 18F-Fluciclovine PET/CT Guidance.

Imaging with novel PET radiotracers has significantly influenced radiotherapy decision making and radiation planning in patients with recurrent prostate cancer (PCa). The purpose of this analysis was to report the final results for management decision changes based on 18F-fluciclovine PET/CT findings and determine whether the decision change trend remained after completion of accrual. Methods: Patients with detectable prostate-specific antigen (PSA) after prostatectomy were randomized to undergo either conventional imaging (CI) only (arm A) or CI plus 18F-fluciclovine PET/CT (arm B) before radiotherapy. In arm B, positivity rates on CI and 18F-fluciclovine PET/CT for detection of recurrent PCa were determined. Final decisions on whether to offer radiotherapy and whether to include only the prostate bed or also the pelvis in the radiotherapy field were based on 18F-fluciclovine PET/CT findings. Radiotherapy decisions before and after 18F-fluciclovine PET/CT were compared. The statistical significance of decision changes was determined using the Clopper-Pearson (exact) binomial method. Prognostic factors were compared between patients with and without decision changes. Results: All 165 patients enrolled in the study had standard-of-care CI and were initially planned to receive radiotherapy. Sixty-three of 79 (79.7%) patients (median PSA, 0.33 ng/mL) who underwent 18F-fluciclovine PET/CT (arm B) had positive findings. 18F-Fluciclovine PET/CT had a significantly higher positivity rate than CI did for the whole body (79.7% vs. 13.9%; P < 0.001), prostate bed (69.6% vs. 5.1%; P < 0.001), and pelvic lymph nodes (38.0% vs. 10.1%; P < 0.001). Twenty-eight of 79 (35.4%) patients had the overall radiotherapy decision changed after 18F-fluciclovine PET/CT; in 4 of 79 (5.1%), the decision to use radiotherapy was withdrawn because of extrapelvic disease detected on 18F-fluciclovine PET/CT. In 24 of 75 (32.0%) patients with a final decision to undergo radiotherapy, the radiotherapy field was changed. Changes in overall radiotherapy decisions and radiotherapy fields were statistically significant (P < 0.001). Overall, the mean PSA at PET was significantly different between patients with and without radiotherapy decision changes (P = 0.033). Conclusion:18F-Fluciclovine PET/CT significantly altered salvage radiotherapy decisions in patients with recurrent PCa after prostatectomy. Further analysis to determine the impact of 18F-fluciclovine PET/CT guidance on clinical outcomes after radiotherapy is in progress.

Best Practices for 18F-Fluciclovine PET/CT Imaging of Recurrent Prostate Cancer: A Guide for Technologists.

18F-fluciclovine is a Food and Drug Administration-approved PET tracer indicated for patients suspected to have recurrent prostate cancer based on a prostate-specific antigen rise after prior therapy. 18F-fluciclovine PET/CT is performed significantly differently from 18F-FDG PET/CT and requires special attention to patient preparation, injection technique, and imaging time. This article aims to provide nuclear medicine technologists with the best-practice guidelines for the 18F-fluciclovine PET/CT protocol.

18F-Fluciclovine Parameters on Targeted Prostate Biopsy Associated with True Positivity in Recurrent Prostate Cancer.

We evaluated 18F-fluciclovine uptake parameters that correlate with true positivity for local recurrence in non-prostatectomy-treated patients. Methods: Twenty-one patients (prostate-specific antigen level, 7.4 ± 6.8 ng/mL) with biochemical recurrence after nonprostatectomy local therapy (radiotherapy and cryotherapy) underwent dual-time-point 18F-fluciclovine (364.1 ± 37.7 MBq) PET/CT from pelvis to diaphragm. Prostatic uptake over background was delineated and coregistered to a prostate-biopsy-planning ultrasound. Transrectal biopsies of 18F-fluciclovine-defined targets were completed using a 3-dimensional visualization and navigation platform. Histologic analyses of lesions were completed. Lesion characteristics including SUVmax, target-to-background ratio (TBR), uptake pattern, and subjective reader's suspicion level were compared between true-positive (malignant) and false-positive (benign) lesions. Univariate analysis was used to determine the association between PET and histologic findings. Receiver-operating-characteristic curves were plotted to determine discriminatory cutoffs for TBR. Statistical significance was set at a P value of less than 0.05. Results: Fifty lesions were identified in 21 patients on PET. Seventeen of 50 (34.0%) targeted lesions in 10 of 21 patients were positive for malignancy. True-positive lesions had a significantly higher SUVmax (6.62 ± 1.70 vs. 4.92 ± 1.27), marrow TBR (2.57 ± 0.81 vs. 1.69 ± 0.51), and blood-pool TBR (4.10 ± 1.17 vs. 2.99 ± 1.01) than false-positive lesions at the early time point (P < 0.01) and remained significant at the delayed time point, except for blood-pool TBR. Focal uptake (odds ratio, 12.07; 95% confidence interval, 2.98-48.80; P < 0.01) and subjective highest suspicion level (odds ratio, 10.91; 95% confidence interval, 1.19-99.69; P = 0.03) correlated with true positivity. Using the receiver-operating-characteristic curve, optimal cutoffs for marrow TBR were 1.9 (area under the curve, 0.82) and 1.8 (area under the curve, 0.85) at early and delayed imaging, respectively. With these cutoffs, 15 of 17 malignant lesions were identified at both time points; however, fewer false-positive lesions were detected at the delayed time point (5/33) than at the early time point (11/33). Conclusion: True positivity of 18F-fluciclovine-targeted prostate biopsy in non-prostatectomy-treated patients correlates with focal uptake, TBR (blood pool and marrow), and subjective highest suspicion level. A marrow TBR of 1.9 at the early time point and 1.8 at the delayed time point had optimal discriminating capabilities. Despite the relatively low intraprostate positive predictive value (34.0%) with 18F-fluciclovine, application of these parameters to interpretative criteria may improve true positivity in the treated prostate.

Feasibility and Initial Results: Fluciclovine Positron Emission Tomography/Ultrasound Fusion Targeted Biopsy of Recurrent Prostate Cancer.

PURPOSE: We assessed the feasibility and cancer detection rate of fluciclovine (18F) positron emission tomography-ultrasound fusion targeted biopsy vs standard template biopsy in the same patient with biochemical failure after nonsurgical therapy for prostate cancer. MATERIALS AND METHODS: A total of 21 patients with a mean ± SD prostate specific antigen of 7.4 ± 6.8 ng/ml and biochemical failure after nonoperative prostate cancer treatment underwent fluciclovine (18F) positron emission tomography-computerized tomography (mean 364.1 ± 37.7 MBq) and planning transrectal prostate ultrasound with 3-dimensional image reconstruction. Focal prostatic activity on positron emission tomography was delineated and co-registered with planning ultrasound. During the subsequent biopsy session computer generated 12-core template biopsies were performed and then fluciclovine defined targets were revealed and biopsied. Histological analysis of template and targeted cores were completed. RESULTS: Template biopsy was positive for malignancy in 6 of 21 patients (28.6%), including 10 of 124 regions and 11 of 246 cores, vs targeted biopsy in 10 of 21 (47.6%), including 17 of 50 regions and 40 of 125 cores. Five of 21 patients had positive findings on targeted biopsy only and 1 of 21 had positive findings on template biopsy only. An additional case was upgraded from Grade Group 2 to 3 on targeted biopsy. Extraprostatic disease was detected in 8 of 21 men (38.1%) with histological confirmation in all 3 who underwent lesion biopsy. CONCLUSIONS: Fluciclovine positron emission tomography real-time ultrasound fusion guidance for biopsy is feasible in patients with biochemical failure after nonsurgical therapy for prostate cancer. It identifies more recurrent prostate cancer using fewer cores compared with template biopsy in the same patient. Further study is required to determine in what manner targeted biopsy may augment template biopsy of recurrent prostate cancer.

Prospective evaluation of fluciclovine (18F) PET-CT and MRI in detection of recurrent prostate cancer in non-prostatectomy patients.

PURPOSE: To investigate the disease detection rate, diagnostic performance and interobserver agreement of fluciclovine (18F) PET-CT and multiparametric magnetic resonance imaging (mpMR) in recurrent prostate cancer. METHODS: Twenty-four patients with biochemical failure after non-prostatectomy definitive therapy, 16/24 of whom had undergone brachytherapy, underwent fluciclovine PET-CT and mpMR with interpretation by expert readers blinded to patient history, PSA and other imaging results. Reference standard was established via a multidisciplinary truth panel utilizing histology and clinical follow-up (22.9 ±â€¯10.5 months) and emphasizing biochemical control. The truth panel was blinded to investigative imaging results. Diagnostic performance and interobserver agreement (kappa) for the prostate and extraprostatic regions were calculated for each of 2 readers for PET-CT (P1 and P2) and 2 different readers for mpMR (M1 and M2). RESULTS: On a whole body basis, the detection rate for fluciclovine PET-CT was 94.7% (both readers), while it ranged from 31.6-36.8% for mpMR. Kappa for fluciclovine PET-CT was 0.90 in the prostate and 1.0 in the extraprostatic regions. For mpMR, kappa was 0.25 and 0.74, respectively. In the prostate, 22/24 patients met the reference standard with 13 malignant and 9 benign results. Sensitivity, specificity and positive predictive value (PPV) were 100.0%, 11.1% and 61.9%, respectively for both PET readers. For mpMR readers, values ranged from 15.4-38.5% for sensitivity, 55.6-77.8% for specificity and 50.0-55.6% for PPV. For extraprostatic disease determination, 18/24 patients met the reference standard. Sensitivity, specificity and PPV were 87.5%, 90.0% and 87.5%, respectively, for fluciclovine PET-CT, while for mpMR, sensitivity ranged from 50 to 75%, specificity 70-80% and PPV 57-75%. CONCLUSION: The disease detection rate for fluciclovine PET-CT in non-prostatectomy patients with biochemical failure was 94.7% versus 31.6-36.8% for mpMR. For extraprostatic disease detection, fluciclovine PET-CT had overall better diagnostic performance than mpMR. For the treated prostate, fluciclovine PET-CT had high sensitivity though low specificity for disease detection, while mpMR had higher specificity, though low sensitivity. Interobserver agreement was also higher with fluciclovine PET-CT compared with mpMR.

Metastatic Male Breast Cancer With Increased Uptake on 18F-Fluciclovine PET/CT Scan.

Prostate imaging with F-labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC, F-fluciclovine) PET/CT scan (Axumin) was recently approved by the US Food and Drug Administration for men with suspected prostate cancer recurrence based on elevated blood prostate-specific antigen levels following prior treatment. We present a rare case of a 77-year-old man with suspected recurrent prostate cancer with an incidental finding of advanced-stage breast cancer showing different degrees of F-fluciclovine uptake.

Automatic segmentation of the prostate on CT images using deep learning and multi-atlas fusion.

Automatic segmentation of the prostate on CT images has many applications in prostate cancer diagnosis and therapy. However, prostate CT image segmentation is challenging because of the low contrast of soft tissue on CT images. In this paper, we propose an automatic segmentation method by combining a deep learning method and multi-atlas refinement. First, instead of segmenting the whole image, we extract the region of interesting (ROI) to delete irrelevant regions. Then, we use the convolutional neural networks (CNN) to learn the deep features for distinguishing the prostate pixels from the non-prostate pixels in order to obtain the preliminary segmentation results. CNN can automatically learn the deep features adapting to the data, which are different from some handcrafted features. Finally, we select some similar atlases to refine the initial segmentation results. The proposed method has been evaluated on a dataset of 92 prostate CT images. Experimental results show that our method achieved a Dice similarity coefficient of 86.80% as compared to the manual segmentation. The deep learning based method can provide a useful tool for automatic segmentation of the prostate on CT images and thus can have a variety of clinical applications.

Multisite Experience of the Safety, Detection Rate and Diagnostic Performance of Fluciclovine (18F) Positron Emission Tomography/Computerized Tomography Imaging in the Staging of Biochemically Recurrent Prostate Cancer.

PURPOSE: Sensitive detection of cancer foci in men experiencing biochemical recurrence following initial treatment of prostate cancer is of great clinical significance with a possible impact on subsequent treatment choice. We describe a multisite experience of the efficacy and safety of the positron emission tomography/computerized tomography agent fluciclovine (18F) after biochemical recurrence. MATERIALS AND METHODS: A total of 596 patients underwent fluciclovine (18F) positron emission tomography/computerized tomography at 4 clinical sites. Detection rate determinations were stratified by the baseline prostate specific antigen value. Diagnostic performance was assessed against a histological reference standard in 143 scans. RESULTS: The subject level fluciclovine (18F) positron emission tomography/computer tomography detection rate was 67.7% (403 of 595 scans). Positive findings were detected in the prostate/bed and pelvic lymph node regions in 38.7% (232 of 599) and 32.6% of scans (194 of 596), respectively. Metastatic involvement outside the pelvis was detected in 26.2% of scans (155 of 591). The subject level detection rate in patients in the lowest quartile for baseline prostate specific antigen (0.79 ng/ml or less) was 41.4% (53 of 128). Of these patients 13 had involvement in the prostate/bed only, 16 had pelvic lymph node involvement without distant disease and 24 had distant metastases. The positive predictive value of fluciclovine (18F) positron emission tomography/computerized tomography scanning for all sampled lesions was 62.2%, and it was 92.3% and 71.8% for extraprostatic and prostate/bed involvement, respectively. Fluciclovine (18F) was well tolerated and the safety profile was not altered following repeat administration. CONCLUSIONS: Fluciclovine (18F) is well tolerated and able to detect local and distant prostate cancer recurrence across a wide range of prostate specific antigen values.

Change in Salvage Radiotherapy Management Based on Guidance With FACBC (Fluciclovine) PET/CT in Postprostatectomy Recurrent Prostate Cancer.

PURPOSE: We explored the influence of FACBC (fluciclovine) PET/CT on the decision to offer radiotherapy and radiotherapy treatment field recommendations in postprostatectomy patients with recurrent prostate cancer. PATIENTS AND METHODS: After obtaining institutional review board approval and informed consent, 87 patients with detectable prostate-specific antigen (PSA) levels were recruited into a prospective clinical trial. After an initial provider-determined radiotherapy plan based on conventional imaging, 44 of 87 patients were randomized to additionally undergo fluciclovine PET/CT. Pre- and post-fluciclovine radiotherapy decisions were compared and changes were noted. Statistical significance of these decision changes was determined. RESULTS: Two of 44 patients in the experimental arm dropped out before fluciclovine scanning. Thirty-four (81.0%) of 42 had positive results on fluciclovine. Overall radiotherapy decision was changed in 17 (40.5%) of 42. Mean PSA, original Gleason score, and prostatectomy-PET interval did not differ significantly between patients with and without radiotherapy decision changes. Two (4.8%) of 42 had the decision for radiotherapy withdrawn due to positive extrapelvic findings. Radiotherapy field decision was changed in 15 (35.7%) of 42. Eleven (73.3%) of 15 had fields changed from prostate bed only to both prostate bed and pelvis, while 4 (26.7%) of 15 had fields changed from both prostate bed and pelvis to prostate bed only. Changes in overall radiotherapy decision and field were statistically significant (P < 0.0001). However, the change in the decision to offer radiotherapy or not was not statistically significant (P = 0.15). CONCLUSIONS: Fluciclovine PET/CT significantly changed radiotherapy management decisions in postprostatectomy patients with recurrent prostate cancer. Further work in determining differences in PSA-free survival is ongoing.

Combining Population and Patient-Specific Characteristics for Prostate Segmentation on 3D CT Images.

Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy.

Anti-3-18F-FACBC (18F-Fluciclovine) PET/CT of Breast Cancer: An Exploratory Study.

UNLABELLED: The purpose of this study was to explore the uptake of the synthetic amino acid analog PET radiotracer anti-3-(18)F-FACBC ((18)F-fluciclovine) in breast lesions with correlation to histologic and immunohistochemical characteristics. METHODS: Twelve women with breast lesions underwent 45-min dynamic PET/CT of the thorax after intravenous administration of 366.3 ± 14.8 (337.44-394.05) MBq of (18)F-fluciclovine. Uptake in the primary lesions at 4 representative time points (5, 17, 29, and 41 min) after injection were correlated with histologic, imaging, and clinical findings. The significance of differences in SUVmax and tumor-to-background ratios between malignant and benign tissue were calculated. Correlations of activity to histologic and immunohistochemical cancer subtypes were made including Ki-67 intensity and Nottingham grade (NG). RESULTS: There were 17 breast lesions (4 benign, 13 malignant) including 7 of 13 invasive ductal, 5 of 13 invasive lobular, and 1 of 13 metaplastic carcinomas. There was a significant difference in mean SUVmax ± SD of malignant (6.2 ± 3.2, 6.0 ± 3.2, 5.7 ± 2.8, and 5.6 ± 3.0) versus benign (1.3 ± 0.6, 1.2 ± 0.5, 1.2 ± 0.6, and 1.1 ± 0.5) lesions at 5, 17, 29, and 41 min, respectively (all P ≤ 0.0001). Tumor-to-background (aorta, normal breast, and marrow) ratios were also significantly higher in malignant than benign breast lesions (all P ≤ 0.02). The highest (18)F-fluciclovine activity seems to be present in triple-negative and NG3 subtypes. Across time points, quantitative Ki-67 had weak positive correlation with SUVmax (R1 = 0.48 [P = 0.03], R2 = 0.44 [P = 0.03], R3 = 0.46 [P = 0.03], R4 = 0.43 [0.06]). In 7 patients, (18)F-fluciclovine PET visualized locoregional and distant spread including that of lobular cancer, though identification of hepatic metastases was limited by physiologic background activity. CONCLUSION: The uptake characteristics of (18)F-fluciclovine are reflective of the histologic and immunohistochemical characteristics in suspected breast lesions with greater activity in malignant versus benign etiology. The data from this exploratory study may be useful to design future studies using (18)F-fluciclovine PET for breast tumor imaging as well as for detection of locoregional and distant spread.

Recurrent prostate cancer detection with anti-3-[(18)F]FACBC PET/CT: comparison with CT.

PURPOSE: To compare the diagnostic performance of the synthetic amino acid analogue PET radiotracer anti-3-[(18)F]FACBC (fluciclovine) with that of CT in the detection of recurrent prostate carcinoma. METHODS: This was a retrospective analysis of 53 bone scan-negative patients with suspected recurrent prostate carcinoma who underwent fluciclovine PET/CT and routine clinical CT within 90 days of each other. The correlation between imaging findings and histology and clinical follow-up was evaluated. Positivity rates and diagnostic performance were calculated for fluciclovine PET/CT and CT. RESULTS: Of 53 fluciclovine PET/CT and 53 CT examinations, 41 (77.4 %) and 10 (18.9 %), respectively, had positive findings for recurrent disease. Positivity rates were higher with fluciclovine PET/CT than with CT at all prostate-specific antigen (PSA) levels, PSA doubling times and original Gleason scores. In the prostate/bed, fluciclovine PET/CT was true-positive in 31 and CT was true-positive in 4 of 51 patients who met the reference standard. In extraprostatic regions, fluciclovine PET/CT was true-positive in 12 and CT was true-positive in 3 of 41 patients who met the reference standard. Of the 43 index lesions used to prove positivity, 42 (97.7 %) had histological proof. In 51 patients with sufficient follow-up to calculate diagnostic performance in the prostate/bed, fluciclovine PET/CT demonstrated a sensitivity of 88.6 %, a specificity of 56.3 %, an accuracy of 78.4 %, a positive predictive value (PPV) of 81.6 %, and a negative predictive value (NPV) of 69.2 %; the respective values for CT were 11.4 %, 87.5 %, 35.3 %, 66.7 % and 31.1 %. In 41 patients with sufficient follow-up to calculate diagnostic performance in extraprostatic regions, fluciclovine PET/CT demonstrated a sensitivity of 46.2 %, a specificity of 100 %, an accuracy of 65.9 %, a PPV of 100 %, and an NPV of 51.7 %; the respective values for CT were 11.5 %, 100 %, 43.9 %, 100 % and 39.5 %. CONCLUSION: The diagnostic performance of fluciclovine PET/CT in recurrent prostate cancer is superior to that of CT and fluciclovine PET/CT provides better delineation of prostatic from extraprostatic recurrence.

Reproducibility and reliability of anti-3-[¹8F]FACBC uptake measurements in background structures and malignant lesions on follow-up PET-CT in prostate carcinoma: an exploratory analysis.

PURPOSE: The aim of this study is to examine the reproducibility of anti-1-amino-3-[(18)F]fluorocyclobutane-1-carboxylic acid (anti-3-[(18)F]FACBC) quantitative measurements in key background structures and untreated malignant lesions. PROCEDURES: Retrospective review of 14 patients who underwent follow-up anti-3-[(18)F]FACBC positron emission tomography-X-ray computed tomography (PET-CT) for prostate carcinoma recurrence. Standard uptake values (SUV) were measured in both original and follow-up scans in key background structures and untreated malignant lesions. Absolute and percent mean difference in SUV between scans and interclass correlation coefficients (ICC) were also computed. RESULTS: Mean (±SD, range) scan interval was 17.4 months (±7.1, 4-29). %Mean difference in SUVmean was <20 % in background structures with low absolute differences. ICCs were >0.6 except for early-phase blood pool (ICC = 0.4). SUVmax in malignant lesions without interim therapy increased or remained stable over time. CONCLUSIONS: Despite variable time interval between scans, FACBC PET-CT demonstrates acceptable reproducibility in key background structures. Untreated malignant lesions showed stable or increased uptake over time. A formal test-retest study is planned.