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Segmentation of the prostate in computed tomography (CT) is used for planning and guidance of prostate treatment procedures. However, due to the low soft-tissue contrast of the images, manual delineation of the prostate on CT is a time-consuming task with high interobserver variability. We developed an automatic, three-dimensional (3-D) prostate segmentation algorithm based on a customized U-Net architecture. Our dataset contained 92 3-D abdominal CT scans from 92 patients, of which 69 images were used for training and validation and the remaining for testing the convolutional neural network model. Compared to manual segmentation by an expert radiologist, our method achieved [Formula: see text] for Dice similarity coefficient (DSC), [Formula: see text] for mean absolute distance (MAD), and [Formula: see text] for signed volume difference ([Formula: see text]). The average recorded interexpert difference measured on the same test dataset was 92% (DSC), 1.1 mm (MAD), and [Formula: see text] ([Formula: see text]). The proposed algorithm is fast, accurate, and robust for 3-D segmentation of the prostate on CT images.

TPS179 Background: Node-positive prostate cancer comprises for approximately 13% of newly-diagnosed patients and represents an aggressive form of the disease, but has been historically understudied in therapeutic clinical trials. Cure rates remain suboptimal for these patients with early stage IV disease, so clinical trials to intensify systemic treatment are warranted. Abiraterone and apalutamide have each demonstrated efficacy in improving metastasis-free survival and/or overall survival in the advanced stage setting, including both castrate-resistant and metastatic castration-sensitive prostate cancer. The mechanisms of action of abiraterone and apalutamide are complementary, and combination therapy has been shown in a prior Phase Ib trial to be safe and well-tolerated. Methods: Patients with pathologic node-positive disease by radical prostatectomy and who subsequently have a detectable PSA are eligible for this randomized controlled trial. All patients are required to receive molecular imaging (FACBC, PSMA, or choline PET scan) at trial entry and must have no radiographic evidence of distant metastasis in order to remain eligible. Eligible patients are randomized 1:1 to (control arm) salvage radiation therapy with 2 years of ADT vs (experimental arm) addition of 2 years of abiraterone/prednisone and apalutamide. The primary endpoint is metastasis-free survival. With a sample size of 586 and with a potential for 10% loss to follow-up, the trial has 90% power with one-sided alpha=0.025 to detect a HR of 0.53 for the experimental arm vs control arm for the primary endpoint. Secondary endpoints include quality of life (EPIC-26, EQ5D-5L, Brief Pain Inventory, PROMIS-Fatigue), overall survival, time to castrate resistance, and other disease-related outcomes. In addition, data will be collected to validate the Decipher score and PAM50-based classification as predictive biomarkers in this node-positive patient population. Trial was activated on March 5, 2020, and is currently enrolling patients. This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA196067 (NRG Oncology Specimen Bank) from the National Cancer Institute (NCI) and Janssen and GenomeDX. Clinical trial information: NCT04134260.

Conventional imaging of prostate cancer has limitations related to the frequently indolent biology of the disease. PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Radiotracers that are in use or under investigation for targeting salient features of prostate cancer include those directed to glucose, choline, acetate, prostate-specific membrane antigen, bombesin, and amino acids. The tumor imaging features of this last class of radiotracers mirror the upregulation of transmembrane amino acid transport that is necessary in carcinomas because of increased amino acid use for energy requirements and protein synthesis. Natural and synthetic amino acids radiolabeled for PET imaging have been investigated in prostate cancer patients. Early work with naturally occurring amino acid-derived radiotracers, such as L-C-11-methionine and L-1-C-11-5-hydroxytryptophan, demonstrated promising results, including greater sensitivity than F-18-FDG for intraprostatic and extraprostatic cancer detection. However, limitations with naturally occurring amino acid-derived compounds, including metabolism of the radiotracer itself, led to the development of synthetic amino acid radiotracers, which are not metabolized and therefore more accurately reflect transmembrane amino acid transport. Of the synthetic amino acid-derived PET radiotracers, anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid (F-18-FACBC or F-18-fluciclovine) has undergone the most promising translation to human use, including the availability of simplified radiosynthesis. Several studies have indicated advantageous biodistribution in the abdomen and pelvis with little renal excretion and bladder activity characteristics beneficial for prostate cancer imaging. Studies have demonstrated improved lesion detection and diagnostic performance of 18F-fluciclovine in comparison with conventional imaging, especially for recurrent prostate cancer, although issues with nonspecific uptake limit the potential role of F-18-fluciclovine in the diagnosis of primary prostate cancer. Although work is ongoing, recently published intrapatient comparisons of F-18-fluciclovine with C-11-choline reported higher overall diagnostic performance of the former, especially for the detection of disease relapse. This review is aimed at providing a detailed overview of amino acid-derived PET compounds that have been studied for use in prostate cancer imaging.

Purpose 18 F-Fluciclovine (anti-1-amino-3-[ 18 F]fluorocyclobutane-1-carboxylic acid) is a novel positron emission tomography (PET)/computed tomography (CT) radiotracer that has demonstrated utility for detection of prostate cancer. Our goal is to report the initial results from a randomized controlled trial of the integration of 18 F-fluciclovine PET-CT into treatment planning for defining prostate bed and lymph node target volumes. Methods and Materials We report our initial findings from a cohort of 41 patients, of the first enrolled on a randomized controlled trial, who were randomized to the 18 F-fluciclovine arm. All patients underwent 18 F-fluciclovine PET-CT for the detection of metabolic abnormalities and high-resolution CT for treatment planning. The 2 datasets were registered first by use of a rigid registration. If soft tissue displacement was observable, the rigid registration was improved with a deformable registration. Each 18 F-fluciclovine abnormality was segmented as a percentage of the maximum standard uptake value (SUV) within a small region of interest around the lesion. The percentage best describing the SUV falloff was integrated in planning by expanding standard target volumes with the PET abnormality. Results In 21 of 55 abnormalities, a deformable registration was needed to map the 18 F-fluciclovine activity into the simulation CT. The most selected percentage was 50% of maximum SUV, although values ranging from 15% to 70% were used for specific patients, illustrating the need for a per-patient selection of a threshold SUV value. The inclusion of 18 F-fluciclovine changed the planning volumes for 46 abnormalities (83%) of the total 55, with 28 (51%) located in the lymph nodes, 11 (20%) in the prostate bed, 10 (18%) in the prostate, and 6 (11%) in the seminal vesicles. Only 9 PET abnormalities were fully contained in the standard target volumes based on the CT-based segmentations and did not necessitate expansion. Conclusions The use of 18 F-fluciclovine in postprostatectomy radiation therapy planning was feasible and led to augmentation of the target volumes in the majority (30 of 41) of the patients studied.

The purpose of this study was to explore the uptake of the synthetic amino acid analog PET radiotracer anti-3-18F-FACBC (18F-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 18F-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 18F-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, 18F-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 18F-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 18F-fluciclovine PET for breast tumor imaging as well as for detection of locoregional and distant spread.

Background Assessment of thyroid cartilage invasion (tumor extension through inner cortex) and thyroid cartilage penetration (tumor involving both the inner and outer cortices of thyroid cartilage) may be challenging with CT (Computed Tomography) and MR imaging (Magnetic Resonance Imaging). Positron Emission Tomography/Computed Tomography (PET/CT) is a non invasive imaging modality that provides both anatomic and metabolic information. Quantitative data obtained from PET/CT, also known as PET/CT parameters, include maximum, mean or peak standardized uptake values (SUVmax, SUVmean, SUVpeak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM) and normalized standardized added metabolic activity (NSAM). Our aim was to examine if FDG PET/CT parameters could differentiate thyroid cartilage invasion from penetration. Methods 50 patients who underwent PET/CT before laryngectomy for squamous cell carcinoma of the larynx, had SUVmax, SUVmean, SUVpeak, TLG, MTV, SAM and NSAM calculated on a dedicated workstation. Univariate and multivariate analysis was performed. ROC analysis was used to determine the ability of PET/CT parameters to predict pathologically proven thyroid cartilage invasion or penetration. Results Of the 50 patients, 50% (25/50 patients) had history of prior radiation therapy. Among the previously irradiated group, 24% had thyroid cartilage invasion and penetration. 8% of the patients in this group had thyroid cartilage invasion only. Among the non-irradiated group, 76% had thyroid cartilage invasion and penetration, 8% had thyroid cartilage invasion without penetration. ROC analysis revealed that none of the PET/CT parameters had enough power to predict thyroid cartilage penetration, but TLG, MTV and SAM had enough power to predict thyroid cartilage invasion in non-irradiated patients. TLG, MTV, SAM and NSAM had enough power to predict thyroid cartilage invasion and penetration in irradiated group. Conclusion TLG, MTV and SAM have enough power to predict thyroid cartilage invasion and penetration in irradiated patients. PET/CT parameters do not have enough potential to differentiate thyroid cartilage invasion from penetration.

The aim of this study was to investigate pre-90Y lung shunt fraction (LSF) as a prognostic factor for overall survival (OS) in 90Y (resin/glass) planning 99mTc-MAA hepatopulmonary shunt studies for primary (hepatocellular carcinoma [HCC], intrahepatic cholangiocarcinoma) and metastatic liver tumors.A total of 366 consecutive patients with primary and metastatic liver tumors underwent pre-90Y shunt study and 90Y radioembolization (mean age, 59.2 years; 55% were male). MAA (mean activity, 3.65 mCi) was administered via the proper hepatic artery. Shunted lung activity was obtained by planar scintigraphy. Median LSF values for primary tumors and metastases were compared with OS from first 90Y therapy via Kaplan-Meier estimation and log-rank test. Correlations between LSF and tumor involvement on baseline cross-sectional imaging were analyzed using Pearson coefficient (r). Patients with LSF of greater than 20% were deemed unsuitable for 90Y.The study included 79 (21.5%) colorectal, 73 (20%) neuroendocrine, 70 (19.1%) HCC, 40 (10.9%) intrahepatic cholangiocarcinoma, 40 (10.9%) melanoma, 20 (5.5%) breast, and 44 (12%) other tumors including lung and pancreatic cancers. Lung shunt fractions of less than 10% and 10% to 20% were observed in 235 patients (64.2%) and 131 patients (35.8%), respectively. Median LSFs were as follows: colorectal cancer (7.60%), neuroendocrine tumor (7.01%), HCC (11.47%), cholangiocarcinoma (7.00%), melanoma (6.00%), breast cancer (7.00%), and others, including lung and pancreatic metastases to the liver (8.36%). The HCC median LSF was significantly higher than that in non-HCC tumors, 11.47% versus 7.10% (P0.001). High LSF (≥ 10%) in HCC correlated with poorer survival from first 90Y compared with low LSF (10%; 4.5 vs 16.4 months, P = 0.003). Similarly, for metastatic disease, high LSF demonstrated significantly poorer survival compared with low LSF in colorectal liver metastases (13.5 vs 7.0 months, P = 0.013), neuroendocrine liver metastases (33.0 vs 9.1 months, P0.001), and melanoma liver metastases (12.0 vs 5.0 months, P = 0.03). No correlation between tumor burden on cross-sectional imaging and LSF was observed (r = 0.35).In patients who are candidates for 90Y therapy, higher LSF is a poor prognostic factor for OS in HCC and metastatic liver tumors.

217 Background: Neuroendocrine transformation (NE) of prostate cancer is difficult to diagnose and treat. 68Ga-DOTATATE PET is useful to detect well-differentiated neuroendocrine tumors, but its application in prostate cancer is not well understood. We evaluated DOTATATE PET in patients with mCRPC and suspected or known NE. Methods: DOTATATE PET/CT were performed in 17 patients with mCRPC. Summed SUVmax of up to 5 bone and 5 soft tissue lesions in each patient were correlated with histologic presence of NE and response to standard of care treatment and clinical outcome (NCT03448458). Results: Mean age was 62.3±9.2 years. Median PSA was 39.0 ng/ml. 2/17 patients had biopsy proven NE. 1/17 was found to have squamous cell cancer and therefore excluded from analysis. 2 patients with NE had platinum-based chemotherapy. Of the 14 patients without NE, 7/14 received enzalutamide or abiraterone, and 7/14 received taxane based chemotherapy after DOTATATE PET. On PET, all patients had at least one lesion (median 7 [interquartile range 6-9]) with uptake. 11/16 patients had bone and visceral/nodal lesions, 4/16 had only bone lesions, and 1 had only nodal disease. Summed SUVmax was significantly higher in 2/16 patients with proven NE compared to the 14/16 non-NE patients (99.1± 16.5 ng/ml vs 48.4± 40.6 ng/ml; p=0.04). There was no correlation between summed SUVmax and PSA. Follow-up was available in 15/16 patients. SUVmax was higher in patients who did not respond to treatment, however, the trend was non-significant (69.5 ± 46.6 vs 39.3 ± 29.6; p=0.20). There was no significant association between survival and DOTATATE uptake. 6/16 patients had next generation sequencing. Of these, 1 patient without NE had BRCA2 mutation, and also had the highest summed uptake in this study. Conclusions: DOTATATE uptake is higher in mCRPC patients with NE or with BRCA mutation. Uptake was higher in patients who did not respond to standard of care treatment, though this was a nonsignificant trend, possibly due to small sample size. Larger studies are therefore recommended. Clinical trial information: NCT03448458.

PURPOSE: To develop an automated cone-beam computed tomography (CBCT) multi-organ segmentation method for potential CBCT-guided adaptive radiation therapy workflow. METHODS AND MATERIALS: The proposed method combines the deep leaning-based image synthesis method, which generates magnetic resonance images (MRIs) with superior soft-tissue contrast from on-board setup CBCT images to aid CBCT segmentation, with a deep attention strategy, which focuses on learning discriminative features for differentiating organ margins. The whole segmentation method consists of 3 major steps. First, a cycle-consistent adversarial network (CycleGAN) was used to estimate a synthetic MRI (sMRI) from CBCT images. Second, a deep attention network was trained based on sMRI and its corresponding manual contours. Third, the segmented contours for a query patient was obtained by feeding the patient’s CBCT images into the trained sMRI estimation and segmentation model. In our retrospective study, we included 100 prostate cancer patients, each of whom has CBCT acquired with prostate, bladder and rectum contoured by physicians with MRI guidance as ground truth. We trained and tested our model with separate datasets among these patients. The resulting segmentations were compared with physicians’ manual contours. RESULTS: The Dice similarity coefficient and mean surface distance indices between our segmented and physicians’ manual contours (bladder, prostate, and rectum) were 0.95±0.02, 0.44±0.22 mm, 0.86±0.06, 0.73±0.37 mm, and 0.91±0.04, 0.72±0.65 mm, respectively. CONCLUSION: We have proposed a novel CBCT-only pelvic multi-organ segmentation strategy using CBCT-based sMRI and validated its accuracy against manual contours. This technique could provide accurate organ volume for treatment planning without requiring MR images acquisition, greatly facilitating routine clinical workflow.

The American College of Radiology (ACR) and American College of Nuclear Medicine (ACNM) collaborated to develop a clinical practice document for the performance of fluciclovine positron-emission tomography (PET) / computed tomography (CT) in the evaluation of patients with suspected prostate cancer recurrence based on the elevation of prostate-specific antigen (PSA) level (biochemical recurrence) after prior therapy. Prostate cancer is the third leading cause of cancer death in the United States. Up to 50% of patients diagnosed with prostate cancer will develop biochemical failure after initial therapy. The differentiation of local from extraprostatic recurrence plays a critical role in patient management. The use of functional imaging targeting features of cancer metabolism has proven highly useful in this regard. Amino acid transport is upregulated in prostate cancer. Fluciclovine (anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid, FACBC, Axumin™) is an artificial amino acid PET tracer which demonstrates utility in the diagnosis of recurrent prostate cancer with significant added value to conventional imaging.

This review summarizes novel imaging in the management of prostate cancer including multiparametric MRI, PET-CT scans with different radiotracers including 11C-acetate, 11C-choline, 18F-choline, 18F sodium fluoride, prostate-specific membrane antigen, and anti-1-amino-3-[18F] fluorocyclobutane-1-carboxylic acid (fluciclovine).

Prostate segmentation in computed tomography (CT) images is useful for planning and guidance of the diagnostic and therapeutic procedures. However, the low soft-tissue contrast of CT images makes the manual prostate segmentation a time-consuming task with high inter-observer variation. We developed a semi-automatic, three-dimensional (3D) prostate segmentation algorithm using shape and texture analysis and have evaluated the method against manual reference segmentations. In a training data set we defined an inter-subject correspondence between surface points in the spherical coordinate system. We applied this correspondence to model the globular and smoothly curved shape of the prostate with 86, well-distributed surface points using a point distribution model that captures prostate shape variation. We also studied the local texture difference between prostate and non-prostate tissues close to the prostate surface. For segmentation, we used the learned shape and texture characteristics of the prostate in CT images and we used a set of user inputs for prostate localization. We trained our algorithm using 23 CT images and tested it on 10 images. We evaluated the results compared with those of two experts' manual reference segmentations using different error metrics. The average measured Dice similarity coefficient (DSC) and mean absolute distance (MAD) were 88 ± 2% and 1.9 ± 0.5 mm, respectively. The averaged inter-expert difference measured on the same dataset was 91 ± 4% (DSC) and 1.3 ± 0.6 mm (MAD). With no prior intra-patient information, the proposed algorithm showed a fast, robust and accurate performance for 3D CT segmentation.

PURPOSE: The prospective, multicenter LOCATE ((18)F Fluciclovine [FACBC] PET/ CT in Patients with Rising PSA after Initial Prostate Cancer Treatment) trial assessed the impact of positron emission tomography/computerized tomography with (18)F-fluciclovine on treatment plans in patients with biochemical recurrence of prostate cancer after primary therapy with curative intent. MATERIALS AND METHODS: Men who had undergone curative intent treatment of histologically confirmed prostate cancer but who were suspected to have recurrence based on rising prostate specific antigen levels were enrolled prospectively. Each man had negative or equivocal findings on standard of care imaging. (18)F-fluciclovine positron emission tomography/computerized tomography was performed according to standardized protocols. Treating physicians completed a questionnaire regarding the patient treatment plan before and after scanning, recording changes to the treatment modality (eg salvage radiotherapy to systemic androgen deprivation therapy) as major and changes in a modality (eg modified radiotherapy fields) as other. RESULTS: Between June 2016 and May 2017, 213 evaluable patients with a median age of 67 years and median prostate specific antigen 1.00 ng/ml were enrolled in study. (18)F-fluciclovine avid lesions were detected in 122 of the 213 patients (57%). Overall 126 of the 213 patients (59%) had a change in management after the scan, which were major in 98 of 126 (78%) and in 88 (70%) were informed by positive positron emission tomography/computerized tomography findings. The most frequent major changes were from salvage or noncurative systemic therapy to watchful waiting (32 of 126 cases or 25%), from noncurative systemic therapy to salvage therapy (30 of 126 or 24%) and from salvage therapy to noncurative systemic therapy (11 of 126 or 9%). CONCLUSIONS: (18)F-fluciclovine positron emission tomography/computerized tomography detected 1 or more recurrence sites in the majority of men with biochemical recurrence, frequently resulting in major changes to management plans. Future studies will be planned to determine whether a management change leads to improved outcomes.

Amino acids are an alternate energy source to glucose and amino acid metabolism is upregulated in multiple malignancies, including breast cancers. Multiple amino acid radiotracers have been utilized to image breast cancer with unique strengths and weaknesses. (11)C-Methionine uptake correlates with S phase fraction in breast cancer and may be useful for evaluation of treatment response. Invasive lobular breast cancers may demonstrate greater (18)F-fluciclovine avidity than (18)F-FDG avidity. Thus, different histologic subtypes of breast cancer may utilize diverse metabolic pathways and may be better imaged by different tracers.

The objective of our study was to study patterns of services rendered by U.S. physicians who self-identify as nuclear medicine (NM) specialists.Recent Medicare physician claims and demographic files were obtained and linked. NM specialists were defined as physicians self-identifying NM as their primary specialty on claims or as any of their specialties during enrollment. Using other self-identified specialties, we classified physicians as nuclear radiologists, nuclear cardiologists, exclusively NM physicians, or Others. Our primary outcome measure was the percentage of NM effort (in work relative value units [WRVUs]) per physician per specialty group. Secondary outcome measures included physician sociodemographic parameters and most common uniquely rendered services.Nationally, 1583 physicians self-identified as NM specialists during the calendar years 2012 through 2015. The distribution of WRVUs attributed to NM varied widely by specialty group; most nuclear radiologists and nuclear cardiologists devoted 10% or less of their effort to NM services whereas most NM physicians devoted 90% or more of their effort to NM services. NM specialists were most commonly nuclear radiologists (52.2%) and men (80.3%) and practiced in urban (98.4%) and nonacademic settings (62.9%). NM physicians interpreted more general NM studies, nuclear radiologists interpreted more cross-sectional imaging studies, and nuclear cardiologists interpreted mostly nuclear cardiology studies, with a majority of their overall work attributed to clinical evaluation and management (E/M). E/M services accounted for less than 2% of WRVUs for both nuclear radiologists and NM physicians.The work patterns of U.S. NM specialists is highly variable. Most NM physicians practice 90% or more NM, whereas most nuclear radiologists and nuclear cardiologists practice 10% or less NM. Commonly performed services vary considerably by specialty group.

Background The ability to accurately and non-invasively distinguish high-grade glioma from low-grade glioma remains a challenge despite advances in molecular and magnetic resonance imaging. We investigated the ability of fluciclovine (18F) PET as a means to identify and distinguish these lesions in patients with known gliomas and to correlate uptake with Ki-67. Results Sixteen patients with a total of 18 newly diagnosed low-grade gliomas (n = 6) and high grade gliomas (n = 12) underwent fluciclovine PET imaging after histopathologic assessment. Fluciclovine PET analysis comprised tumor SUVmax and SUVmean, as well as metabolic tumor thresholds (1.3*, 1.6*, 1.9*) to normal brain background (TBmax, and TBmean). Comparison was additionally made to the proliferative status of the tumor as indicated by Ki-67 values. Fluciclovine uptake greater than normal brain parenchyma was found in all lesions studied. Time activity curves demonstrated statistically apparent flattening of the curves for both high-grade gliomas and low-grade gliomas starting 30 min after injection, suggesting an influx/efflux equilibrium. The best semiquantitative metric in discriminating HGG from LGG was obtained utilizing a metabolic 1 tumor threshold of 1.3* contralateral normal brain parenchyma uptake to create a tumor: background (TBmean1.3) cutoff of 2.15 with an overall sensitivity of 97.5% and specificity of 95.5%. Additionally, using a SUVmax > 4.3 cutoff gave a sensitivity of 90.9% and specificity of 97.5%. Tumor SUVmean and tumor SUVmax as a ratio to mean normal contralateral brain were both found to be less relevant predictors of tumor grade. Both SUVmax (R = 0.71, p = 0.0227) and TBmean (TBmean1.3: R = 0.81, p = 0.00081) had a high correlation with the tumor proliferative index Ki-67. Conclusions Fluciclovine PET produces high-contrast images between both low-grade and high grade gliomas and normal brain by visual and semiquantitative analysis. Fluciclovine PET appears to discriminate between low-grade glioma and high-grade glioma, but must be validated with a larger sample size. Electronic supplementary material The online version of this article (10.1186/s13550-018-0415-3) contains supplementary material, which is available to authorized users.

We investigated if previously demonstrated inhibition of fluciclovine ((18)F) in vitro could be replicated in a PC3-Luc xenograft mouse model. Following intratumoral injection of 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), alpha-(methylamino)isobutyric acid (MeAIB) or saline, fluciclovine PET tumor-to-background activity was 43.6 (± 5.4)% and 25.3 (± 5.2)% lower in BCH (n = 6) and MeAIB (n = 5) injected PC3 Luc xenografts, respectively, compared to saline-injected controls (n = 2). Partial inhibition of fluciclovine uptake by BCH and MeAIB can be demonstrated in vivo similar to previous in vitro modeling.

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 ± 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.

Muscle-invasive bladder cancer (MIBC) has a tendency toward urothelial multifocality and is at risk for local and distant spread, most commonly to the lymph nodes, bone, lung, liver, and peritoneum. Pretreatment staging of MIBC should include imaging of the urothelial upper tract for synchronous lesions; imaging of the chest, abdomen, and pelvis for metastases; and MRI pelvis for local staging. CT abdomen and pelvis without and with contrast (CT urogram) is recommended to assess the urothelium and abdominopelvic organs. Pelvic MRI can improve local bladder staging accuracy. Chest imaging is also recommended with chest radiograph usually being adequate. FDG-PET/CT may be appropriate to identify nodal and metastatic disease. Chest CT may be useful in high-risk patients and those with findings on chest radiograph. Nonurogram CT and MRI of the abdomen and pelvis are usually not appropriate, and neither is radiographic intravenous urography, Tc-99m whole body bone scan, nor bladder ultrasound for pretreatment staging of MIBC. 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.

PET is a functional imaging method that can exploit various aspects of tumor biology to enable greater detection of prostate cancer than can be provided by morphologic imaging alone. Anti-1-amino-3-(18)F-flurocyclobutane-1-carboxylic acid ((18)F-fluciclovine) is a nonnaturally occurring amino acid PET radiotracer that was recently approved by the U.S. Food and Drug Administration for detection of suspected recurrent prostate cancer. The tumor-imaging features of this radiotracer mirror the upregulation of transmembrane amino acid transport that occurs in prostate cancer because of increased amino acid metabolism for energy and protein synthesis. This continuing medical education article provides an overview on (18)F-fluciclovine PET diagnostic capabilities for primary and metastatic disease, including reviews of published comparisons to conventional imaging and other molecular imaging agents. Additionally, the imaging procedure and image interpretation are detailed, including physiologic and pathologic uptake patterns and pitfalls.

We developed a longitudinal care coordination service to proactively deliver high-quality and family-centered care in patients receiving radioiodine therapy for thyroid cancer. In an iterative, multidisciplinary team manner, a pretherapy consultation service, which included scripted interactions, documentation, and checklists for quality control, evolved over time into a robust patient-centered longitudinal care coordination nuclear medicine service. Radiation safety precautions, the rationale for therapy, and management of patient expectations were addressed through the initial consultation, and discharge and posttreatment care were managed during subsequent follow-up. The patient-physician relationship created during longitudinal nuclear medicine therapy care is one tool to help counteract the growing commoditization of radiology. This article describes the process that the nuclear medicine specialists in our department established to enhance radiologist value by providing both exceptional thyroid cancer treatment and continuity of care.

This study was designed to seek associations between positron emission tomography/computed tomography (PET/CT) parameters, contrast enhanced neck computed tomography (CECT) and pathological findings, and to determine the potential prognostic value of PET/CT and CECT parameters in oral cavity squamous cell carcinoma (OCSCC).36 OCSCC patients underwent staging PET/CT and 30/36 of patients had CECT. PET/CT parameters were measured for the primary tumor and the hottest involved node, including maximum, mean, and peak standardized uptake values (SUV max, SUV mean, and SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), standardized added metabolic activity (SAM), and normalized standardized added metabolic activity (N SAM). Qualitative assessment of PET/CT and CECT were also performed. Pathological outcomes included: perineural invasion, lymphovascular invasion, nodal extracapsular spread, grade, pathologic T and N stages. Multivariable logistic regression models were fit for each parameter and outcome adjusting for potentially confounding variables. Multivariable Cox proportional hazards models were used for progression free survival (PFS), locoregional recurrence free survival (LRFS), overall survival (OS) and distant metastasis free survival (DMFS).In multivariable analysis, patients with high (≥ median) tumor SUV max (OR 6.3), SUV mean (OR 6.3), MTV (OR 19.0), TLG (OR 19.0), SAM (OR 11.7) and N SAM (OR 19.0) had high pathological T-stage (T3/T4) (p0.05). Ring/heterogeneous pattern on CECT qualitative assessment was associated with worse DMFS and OS.High PET/CT parameters were associated with pathologically advanced T stage (T3/T4). Qualitative assessment of CECT has prognostic value. PET/CT parameters did not predict clinical outcome.

Clinicians may order Octreoscan or positron emission tomography (PET) scan for staging patients with neuroendocrine tumors (NETs). (111)In-Octreoscan (Octreoscan) identifies tumors by radiolabeled targeting of somatostatin receptors, while 18F-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) measures differential tissue glucose transport. We assessed the sensitivity of both nuclear imaging modalities with pathologic correlation to define the best initial choice for NET staging after standard cross-sectional imaging.We identified all patients diagnosed with NETs of gastrointestinal or pancreatic origin who underwent nuclear imaging staging by Octreoscan and/or PET from 2000 to 2013. Imaging results were correlated with tumor differentiation and grade of pathology specimens.Imaging and pathology results were identified for 153 patients. Of these, 131 underwent Octreoscan, 43 underwent PET, and 21 patients had both performed. Overall sensitivity of Octreoscan and PET for NET detection was similar (77 vs. 72 %; p = not significant). For well-differentiated NETs, Octreoscan (n = 124) demonstrated sensitivity of 80 vs. 60 % (p = 0.28) for PET (n = 30). For poorly-differentiated NETs, Octreoscan (n = 7) proved significantly less sensitive than PET (n = 13) (57 vs. 100 %; p = 0.02). The sensitivity of Octreoscan versus PET varied similarly when analyzed by WHO tumor grade: Grade 1 (79 vs. 52 %; p = 0.16), Grade 2 (85 vs. 86 %; p = not significant), and Grade 3 (57 vs. 100 %; p = 0.02).Tumor differentiation can be used to guide selection of nuclear imaging modalities for staging gastrointestinal and pancreatic NETs. Octreoscan appears more sensitive than (18)FDG-PET for well-differentiated NETs, whereas (18)FDG-PET demonstrates superior sensitivity for poorly-differentiated NETs.

Advanced prostate cancer presents a diagnostic challenge to clinicians. Although prostate cancer prevalence may be declining, it still remains the second highest cause of cancer death. The treatment of prostate cancer in advanced stages requires significant intervention, including surgery, chemotherapy, radiotherapy, and supportive care, and remains a major public health problem. Earlier detection and identification of advanced prostate cancer is a diagnostic dilemma. In this summary, we review the status and future direction of molecular imaging for advanced prostate cancer (Figs. 1 and 2). Clinical imaging tools employed in the diagnosis of prostate cancer include transrectal ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and bone scans. Unfortunately, the likelihood of disease detection with these modalities is low. Surgical series have shown that transrectal ultrasound may understage disease 30% of the time. Ultrasound is a mainstay of therapy, but the accuracy in cancer diagnosis is between 52% and 62%, suggesting limitations to universalize this technique for many clinical scenarios. Transrectal ultrasound may also be used when patients have failed initial therapy and other imaging has not detected disease, but similar limitations persist. MRI is commonly used at diagnosis and on recurrence. The T2 sequence is best suited for evaluating disease in the prostate, with areas of low intensity suggestive of prostate cancer vs benign tissue. Overall, MRI is effective in delineating soft tissue and can be an excellent technique for targeted therapy; however, the sensitivity and specificity is variable, especially in the posttherapy and postbiopsy settings. The reported data of diagnostic efficacy are dependent on the study population's methods and the sequencing and programming protocols used. Dynamic contrast-enhanced MRI exhibits improved sensitivity and specificity and may be helpful in delineating tumor from scar but may also be confounded by blood product remnants within the prostate. When evaluating for metastatic disease, a Technetium-99m bone scan is the mainstay of imaging. Published data indicate that routine whole-body bone scan underestimates disease and has low sensitivity and specificity. Choueiri et al reported in the scenario where prostrate-specific antigen (PSA) rises following therapy, and a bone scan, conventional CT, and MRI are used, the chance of detecting disease increases when the PSA is more than 5 ng/mL and the doubling time is

PET Response Criteria for Solid Tumors (PERCIST) were assessed and correlated with survival analysis after resin-based 90Yttrium (90Y) radioembolization therapy for intrahepatic cholangiocarcinoma (ICC).Target and overall PERCIST and Response Criteria for Solid Tumors (RECIST) treatment responses were assessed in consecutive patients treated with Y radioembolization for ICC refractory to standard chemotherapy. Significant measurable tumor was defined as 1 cm or greater in diameter and SUVpeak of 2.5 or greater in targeted and nontargeted lesions. The PERCIST defines complete response as resolution of 18F-FDG uptake within measurable lesions, and partial response as 30% reduction in 18F-FDG peak standardized uptake value in measurable lesions. Objective response included partial response and complete response. Survival analysis by Kaplan-Meier and log-rank proportional models was performed using SPSS software version 20.0 (IBM, Armonk, NY), and significance was set at P0.05.Median overall survival (OS) of 9 consecutive patients (56% women; mean age, 58 years) from 90Y therapy was 21.7 months. At 3 months, PERCIST objective response rate of target lesions was 77.7%, and target objective response on PERCIST correlated significantly to prolonged OS (P = 0.022). Overall objective PERCIST response at 3 months had significant correlation with OS (P = 0.011). Probability of death was significantly higher in overall nonresponders by PERCIST (hazard ratio, 12.3). No objective response was seen with RECIST.In patients with unresectable ICC refractory to standard chemotherapy, PERCIST at 3 months for assessment of imaging response after 90Y radioembolization therapy predict OS.

This paper provides a review on molecular imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI) for prostate cancer detection and its applications in fusion targeted biopsy of the prostate.Literature search was performed through the PubMed database using the keywords "prostate cancer", "MRI/ultrasound fusion", "molecular imaging", and "targeted biopsy". Estimates in autopsy studies indicate that 50% of men older than 50 years of age have prostate cancer. Systematic transrectal ultrasound (TRUS) guided prostate biopsy is considered the standard method for prostate cancer detection and has a significant sampling error and a low sensitivity. Molecular imaging technology and new biopsy approaches are emerging to improve the detection of prostate cancer.Molecular imaging with PET and MRI shows promising results in the early detection of prostate cancer. MRI/TRUS fusion targeted biopsy has become a new clinical standard for the diagnosis of prostate cancer. PET molecular image-directed, three-dimensional ultrasound-guided biopsy is a new technology that has great potential for improving prostate cancer detection rate and for distinguishing aggressive prostate cancer from indolent disease.Molecular imaging and fusion targeted biopsy are active research areas in prostate cancer research.

Qualitative assessment of PET/CT results in post therapy is very important to provide a reproducible and systemic reporting. A recently introduced response criteria, known as the Hopkins criteria showed promising results. Our aim is to externally validate the Hopkins interpretation system to assess therapy response in head and neck squamous cell cancer (HNSCC). The study included 69 biopsy proven HNSCC patients who underwent post therapy PET/CT between 5-24 weeks after completion of therapy. PET/CT images were interpreted by one nuclear medicine physician and one nuclear radiologist, independently. The studies were scored according to the Hopkins criteria for right neck, left neck, primary tumor site, and overall assessment. Scores 1, 2, 3 were considered as negative and scores 4 and 5 were considered as positive for tumors. Inter-reader variability was assessed using percent agreement and Kappa statistics. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and analyzed using Cox proportional hazards regression. Of the 69 patients, 59 (85.5%) were males, with a mean age of 62.8 years. The percent agreement between readers for overall, right neck, left neck, and primary tumor site were 91.3%, 97.6%, 97.6%, 91.3% respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the overall therapy assessment were 66.7%, 87.3%, 33%, 96.5% respectively. Cox univariate regression analysis showed positive primary tumor site scores and overall scores were associated with a higher risk of progression (p

OBJECTIVE. The purpose of this review is to summarize the applications of PET molecular imaging–directed biopsy of a variety of organs in the management of various diseases with a focus on cancers. CONCLUSION. PET can yield metabolic information at the cellular and molecular levels, and PET-directed biopsy is playing an increasing role in the diagnosis and staging of diseases.

18F-fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid) is an amino acid positron emission tomography (PET) tracer used for cancer staging (e.g., prostate and breast). Patients scheduled to undergo amino acid-PET are usually required to fast before PET tracer administration. However, there have been no reports addressing whether fasting improves fluciclovine-PET imaging. In this study, the authors investigated the influence of fasting on fluciclovine-PET using triple-tracer autoradiography with 14C-fluciclovine, [5,6-³H]-2-fluoro-2-deoxy-d-glucose (³H-FDG), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) in a rat breast cancer model of mixed osteolytic/osteoblastic bone metastases in which the animals fasted overnight. Lesion accumulation of each tracer was evaluated using the target-to-background (muscle) ratio. The mean ratios of 14C-fluciclovine in osteolytic lesions were 4.6 ± 0.8 and 2.8 ± 0.6, respectively, with and without fasting, while those for ³H-FDG were 6.9 ± 2.5 and 5.1 ± 2.0, respectively. In the peri-tumor bone formation regions (osteoblastic), where 99mTc-HMDP accumulated, the ratios of 14C-fluciclovine were 4.3 ± 1.4 and 2.4 ± 0.7, respectively, and those of ³H-FDG were 6.2 ± 3.8 and 3.3 ± 2.2, respectively, with and without fasting. These results suggest that fasting before 18F-fluciclovine-PET improves the contrast between osteolytic and osteoblastic bone metastatic lesions and background, as well as 18F-FDG-PET.

18F-fluciclovine (trans-1-amino-3-18F-fluorocyclobutanecarboxylic acid) is an amino acid positron emission tomography (PET) tracer used for cancer staging (e.g., prostate and breast). Patients scheduled to undergo amino acid-PET are usually required to fast before PET tracer administration. However, there have been no reports addressing whether fasting improves fluciclovine-PET imaging. In this study, the authors investigated the influence of fasting on fluciclovine-PET using triple-tracer autoradiography with 14C-fluciclovine, [5,6-3H]-2-fluoro-2-deoxy-d-glucose (3H-FDG), and 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) in a rat breast cancer model of mixed osteolytic/osteoblastic bone metastases in which the animals fasted overnight. Lesion accumulation of each tracer was evaluated using the target-to-background (muscle) ratio. The mean ratios of 14C-fluciclovine in osteolytic lesions were 4.6 ± 0.8 and 2.8 ± 0.6, respectively, with and without fasting, while those for 3H-FDG were 6.9 ± 2.5 and 5.1 ± 2.0, respectively. In the peri-tumor bone formation regions (osteoblastic), where 99mTc-HMDP accumulated, the ratios of 14C-fluciclovine were 4.3 ± 1.4 and 2.4 ± 0.7, respectively, and those of 3H-FDG were 6.2 ± 3.8 and 3.3 ± 2.2, respectively, with and without fasting. These results suggest that fasting before 18F-fluciclovine-PET improves the contrast between osteolytic and osteoblastic bone metastatic lesions and background, as well as 18F-FDG-PET.

The purpose of this study was to evaluate the role of the synthetic amino acid PET radiotracer 18F-fluciclovine in modifying the defined clinical and treatment-planning target volumes in postprostatectomy patients undergoing salvage radiotherapy and to evaluate the resulting dosimetric consequences to surrounding organs at risk. Methods: Ninety-six patients were enrolled in a randomized, prospective intention-to-treat clinical trial for potential salvage radiotherapy for recurrent prostate cancer after prostatectomy. The initial treatment plan was based on the results from conventional abdominopelvic CT and MRI. The 45 patients in the experimental arm also underwent abdominopelvic 18F-fluciclovine PET/CT, and the images were registered with the conventional images to determine whether the results would modify the initial treatment plan. The 51 patients in the control arm did not undergo 18F-fluciclovine PET/CT. For each patient, the clinical and treatment-planning target volumes that would have been treated before 18F-fluciclovine registration were compared with those after registration. For organs at risk (rectum, bladder, and penile bulb), the volumes receiving 40 Gy and 65 Gy before registration were compared with those after registration. Statistical comparisons were made using the paired t test. Acute genitourinary and gastrointestinal toxicity as defined by the Radiation Therapy Oncology Group was compared between the control and experimental arms using the χ2 test. Results: In 24 cases, radiotherapy was planned to a clinical target volume consisting of the prostate bed alone (CTV) (64.8-66.6 Gy). In 21 cases, radiotherapy was planned to a clinical target volume consisting of the pelvis (CTV1) (45.0 Gy) followed by a boost to the prostate bed (CTV2) (19.8-25.2 Gy). In each case, the respective treatment-planning target volume expansion (PTV, PTV1, or PTV2) was 0.8 cm (0.6 cm posterior). With the exception of PTV2, all postregistration volumes were significantly larger than the corresponding preregistration volumes. Analysis of the rectum, bladder, and penile bulb volumes receiving 40 Gy and 60 Gy demonstrated that only the penile bulb volumes were significantly higher after registration. No significant differences in acute genitourinary or gastrointestinal toxicity were observed. Conclusion: Including information from 18F-fluciclovine PET in the treatment-planning process led to significant differences in the defined target volume, with higher doses to the penile bulb but no significant differences in rectal or bladder dose or in acute genitourinary or gastrointestinal toxicity. Longer follow-up is needed to determine the impact of 18F-fluciclovine PET on cancer control and late toxicity endpoints.

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.

Despite the frequent statement that "most men die with prostate cancer, not of it," the reality is that prostate cancer is second only to lung cancer as a cause of death from malignancy in American men. The primary goal during baseline evaluation of prostate cancer is disease characterization, that is, establishing disease presence, extent (local and distant), and aggressiveness. Prostate cancer is usually diagnosed after the finding of a suspicious serum prostate-specific antigen level or digital rectal examination. Tissue diagnosis may be obtained by transrectal ultrasound-guided biopsy or MRI-targeted biopsy. The latter requires a preliminary multiparametric MRI, which has emerged as a powerful and relatively accurate tool for the local evaluation of prostate cancer over the last few decades. Bone scintigraphy and CT are primarily used to detect bone and nodal metastases in patients found to have intermediate- or high-risk disease at biopsy. 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.

Purpose The aim of this study is to examine the reproducibility of anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) quantitative measurements in key background structures and untreated malignant lesions.

Androgens play a crucial role in prostate cancer progression, and trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (anti-[(18) F]FACBC) are used for visualization of prostate cancer. We examined the effect of androgen on the expression of amino acid transporters related to anti-[(18)F]FACBC transport and uptake of trans-1-amino-3-fluoro-[1-(14)C]cyclobutanecarboxylic acid (anti-[(14)C]FACBC).Expression of amino acid transporters and uptake of anti-[(14)C]FACBC in androgen receptor (AR)-positive LNCaP and AR-negative DU145 human prostate cancer cells cultured with/without 5α-dihydrotestosterone (DHT) and the effect of bicalutamide, an AR antagonist, on DHT-associated changes were investigated.DHT stimulated the expression of amino acid transporters ASCT2, SNAT5, 4F2 heavy chain, and LAT3 in LNCaP but not in DU145 cells. Anti-[(14)C]FACBC uptake was enhanced, in a DHT-dependent manner, in LNCaP cells only.DHT enhanced the expression of ASCT2, the transporter responsible for anti-[(18)F]FACBC uptake, thereby increasing anti-[(14)C]FACBC uptake in AR-positive LNCaP cells. Androgen-mediated induction may contribute to the distinct anti-[(18)F]FACBC accumulation pattern in prostate cancer.

Purpose: We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[18F]FACBC compared to ProstaScint® (111In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma.Materials and Methods: A total of 93 patients met study inclusion criteria who underwent anti-3-[18F]FACBC positron emission tomography-computerized tomography plus 111In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease.Results: In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[18F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to 111In-capromab pend...

Purpose To assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases. Methods and Materials Yttrium-90 ( 90 Y) bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) acquired after 90 Y radioembolization was convolved with published 90 Y Monte Carlo estimated dose deposition kernels to create a three-dimensional dose distribution. Dose-volume histograms were calculated for tumor volumes manually defined from magnetic resonance imaging or PET/CT imaging. Tumor response was assessed by absolute reduction in maximum standardized uptake value (SUV max ) and total lesion glycolysis (TLG). Results Seven patients with 30 tumors treated with 90 Y for hepatic metastatic melanoma with available 90 Y SPECT/CT and PET/CT before and after treatment were identified for analysis. The median (range) for minimum, mean, and maximum dose per tumor volume was 16.9 Gy (5.7–43.5 Gy), 28.6 Gy (13.8–65.6 Gy) and 36.6 Gy (20–124 Gy), respectively. Response was assessed by fluorodeoxyglucose PET/CT at a median time after treatment of 2.8 months (range, 1.2–7.9 months). Mean tumor dose ( P = .03) and the percentage of tumor volume receiving ≥ 50 Gy ( P max , whereas maximum tumor dose predicted for decrease in tumor TLG ( P Conclusions Volumetric dose calculations showed a statistically significant association with metabolic tumor response. The significant dose-response relationship points to the clinical utility of patient-specific absorbed dose calculations for radionuclide therapy.

Purpose To investigate a simple semiquantitative method to estimate yttrium-90 ( 90 Y) dose delivered with radioembolization to infiltrative hepatocellular carcinoma (HCC). Materials and Methods In a prospective study, patients with infiltrative HCC and portal vein thrombosis (PVT) underwent glass-based 90 Y radioembolization including technetium-99m macroaggregated albumin ( 99m Tc-MAA) hepatopulmonary shunt study before therapy and bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) after 90 Y radioembolization. Baseline magnetic resonance imaging was coregistered with 99m Tc-MAA and bremsstrahlung SPECT/CT imaging separately. Unit tumor activity ( 90 Y radioactivity delivered to each cubic centimeter of tumor) was estimated based on a lobar infusion approach. Correlation between proportions of 99m Tc-MAA and 90 Y delivered to the tumor was investigated. Survival analysis was performed using Kaplan-Meier estimations. Results 90 Y therapy was administered in 18 consecutive patients (median age, 55.3 y; mean tumor volume, 588 cm 3 ). Higher intratumoral 90 Y dose predicted prolonged survival, with 13.2-month median survival in patients with HCC and mean 90 Y dose of ≥ 100 Gy versus 4.6-month median survival for other patients ( P 90 Y dose, 51.9% was delivered to the targeted tumors compared with 74.1% of 99m Tc-MAA with linear correlation between biodistribution of 99m Tc-MAA and 90 Y observed (Pearson r = 0.774, P Conclusions The findings in this study suggest that approximately 50% of administered 90 Y dose is taken up by targeted infiltrative HCC with PVT. Intratumoral 90 Y dose ≥ 100 Gy in unresectable infiltrative HCC via a lobar intraarterial approach is a positive prognostic factor for survival.

Conventional anatomical imaging with CT and MRI has limitations in the evaluation of prostate cancer. PET is a powerful imaging technique, which can be directed toward molecular targets as diverse as glucose metabolism, density of prostate-specific membrane antigen receptors, and skeletal osteoblastic activity. Although 2-deoxy-2- 18 F-FDG-PET is the mainstay of molecular imaging, FDG has limitations in typically indolent prostate cancer. Yet, there are many useful and emerging PET tracers beyond FDG, which provide added value. These include radiotracers interrogating prostate cancer via molecular mechanisms related to the biology of choline, acetate, amino acids, bombesin, and dihydrotestosterone, among others. Choline is used for cell membrane synthesis and its metabolism is upregulated in prostate cancer. 11 C-choline and 18 F-choline are in wide clinical use outside the United States, and they have proven most beneficial for detection of recurrent prostate cancer. 11 C-acetate is an indirect biomarker of fatty acid synthesis, which is also upregulated in prostate cancer. Imaging of prostate cancer with 11 C-acetate is overall similar to the choline radiotracers yet is not as widely used. Upregulation of amino acid transport in prostate cancer provides the biologic basis for amino acid–based radiotracers. Most recent progress has been made with the nonnatural alicyclic amino acid analogue radiotracer anti -1-amino-3- 18 F-fluorocyclobutane-1-carboxylic acid (FACBC or fluciclovine) also proven most useful for the detection of recurrent prostate cancer. Other emerging PET radiotracers for prostate cancer include the bombesin group directed to the gastrin-releasing peptide receptor, 16β- 18 F-fluoro-5α-dihydrotestosterone (FDHT) that binds to the androgen receptor, and those targeting the vasoactive intestinal polypeptide receptor 1 (VPAC-1) and urokinase plasminogen activator receptor (uPAR), which are also overexpressed in prostate cancer.

Positron emission tomography (PET) with amino acid tracers is useful for the visualization and assessment of therapeutic effects on gliomas. Our purpose is to elucidate the transport mechanisms of trans-1-amino-3-[¹⁸F]fluorocyclobutanecarboxylic acid (anti-[¹⁸F]FACBC) and L-[methyl-¹¹C]methionine ([¹¹C]Met) in normal human astrocytes (NHA), low-grade (Hs683, SW1088), and high-grade (U87MG, T98G) human glioma cell lines. Because the short half-lives of fluorine-18 and carbon-11 are inconvenient for in vitro experiments, trans-1-amino-3-fluoro[1-¹⁴C]cyclobutanecarboxylic acid (anti-[¹⁴C]FACBC) and L-[methyl-¹⁴C]methionine ([¹⁴C]Met) were used instead of the PET tracers. Time-course uptake experiments showed that uptake of anti-[¹⁴C]FACBC was 1.4-2.6 times higher than that of [¹⁴C]Met in NHA and low-grade glioma cells, and was almost equal to that of [¹⁴C]Met in high-grade glioma cells. To identify the amino acid transporters (AATs) involved in the transport of anti-[¹⁴C]FACBC and [¹⁴C]Met, we carried out competitive inhibition experiments using synthetic/naturally-occurring amino acids as inhibitors. We found that anti-[¹⁴C]FACBC uptake in the presence of Na⁺ was strongly inhibited by L-glutamine and L-serine (the substrates for ASC system AATs), whereas L-phenylalanine and 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (BCH, the substrates for L system AATs) robustly inhibited Na⁺-independent anti-[¹⁴C]FACBC uptake. Regardless of Na⁺, [¹⁴C]Met uptake was inhibited strongly by L-phenylalanine and BCH. Moreover, the exchange transport activity of L-glutamine for anti-[¹⁴C]FACBC was stronger than that of BCH in the presence of Na⁺, whereas that for [¹⁴C]Met was almost equal to BCH. These results demonstrate that ASC and L are important transport systems for anti-[¹⁸F]FACBC uptake, while system L is predominantly involved in [¹¹C]Met transport in human astrocytes and glioma cells.