TMTV-Net: fully automated total metabolic tumor volume segmentation in lymphoma PET/CT images - a multi-center generalizability analysis.

PURPOSE: Total metabolic tumor volume (TMTV) segmentation has significant value enabling quantitative imaging biomarkers for lymphoma management. In this work, we tackle the challenging task of automated tumor delineation in lymphoma from PET/CT scans using a cascaded approach. METHODS: Our study included 1418 2-[18F]FDG PET/CT scans from four different centers. The dataset was divided into 900 scans for development/validation/testing phases and 518 for multi-center external testing. The former consisted of 450 lymphoma, lung cancer, and melanoma scans, along with 450 negative scans, while the latter consisted of lymphoma patients from different centers with diffuse large B cell, primary mediastinal large B cell, and classic Hodgkin lymphoma cases. Our approach involves resampling PET/CT images into different voxel sizes in the first step, followed by training multi-resolution 3D U-Nets on each resampled dataset using a fivefold cross-validation scheme. The models trained on different data splits were ensemble. After applying soft voting to the predicted masks, in the second step, we input the probability-averaged predictions, along with the input imaging data, into another 3D U-Net. Models were trained with semi-supervised loss. We additionally considered the effectiveness of using test time augmentation (TTA) to improve the segmentation performance after training. In addition to quantitative analysis including Dice score (DSC) and TMTV comparisons, the qualitative evaluation was also conducted by nuclear medicine physicians. RESULTS: Our cascaded soft-voting guided approach resulted in performance with an average DSC of 0.68 ± 0.12 for the internal test data from developmental dataset, and an average DSC of 0.66 ± 0.18 on the multi-site external data (n = 518), significantly outperforming (p < 0.001) state-of-the-art (SOTA) approaches including nnU-Net and SWIN UNETR. While TTA yielded enhanced performance gains for some of the comparator methods, its impact on our cascaded approach was found to be negligible (DSC: 0.66 ± 0.16). Our approach reliably quantified TMTV, with a correlation of 0.89 with the ground truth (p < 0.001). Furthermore, in terms of visual assessment, concordance between quantitative evaluations and clinician feedback was observed in the majority of cases. The average relative error (ARE) and the absolute error (AE) in TMTV prediction on external multi-centric dataset were ARE = 0.43 ± 0.54 and AE = 157.32 ± 378.12 (mL) for all the external test data (n = 518), and ARE = 0.30 ± 0.22 and AE = 82.05 ± 99.78 (mL) when the 10% outliers (n = 53) were excluded. CONCLUSION: TMTV-Net demonstrates strong performance and generalizability in TMTV segmentation across multi-site external datasets, encompassing various lymphoma subtypes. A negligible reduction of 2% in overall performance during testing on external data highlights robust model generalizability across different centers and cancer types, likely attributable to its training with resampled inputs. Our model is publicly available, allowing easy multi-site evaluation and generalizability analysis on datasets from different institutions.

PSMA-Hornet: Fully-automated, multi-target segmentation of healthy organs in PSMA PET/CT images.

BACKGROUND: Prostate-specific membrane antigen (PSMA) PET imaging represents a valuable source of information reflecting disease stage, response rate, and treatment optimization options, particularly with PSMA radioligand therapy. Quantification of radiopharmaceutical uptake in healthy organs from PSMA images has the potential to minimize toxicity by extrapolation of the radiation dose delivery towards personalization of therapy. However, segmentation and quantification of uptake in organs requires labor-intensive organ delineations that are often not feasible in the clinic nor scalable for large clinical trials. PURPOSE: In this work we develop and test the PSMA Healthy organ segmentation network (PSMA-Hornet), a fully-automated deep neural net for simultaneous segmentation of 14 healthy organs representing the normal biodistribution of [18 F]DCFPyL on PET/CT images. We also propose a modified U-net architecture, a self-supervised pre-training method for PET/CT images, a multi-target Dice loss, and multi-target batch balancing to effectively train PSMA-Hornet and similar networks. METHODS: The study used manually-segmented [18 F]DCFPyL PET/CT images from 100 subjects, and 526 similar images without segmentations. The unsegmented images were used for self-supervised model pretraining. For supervised training, Monte-Carlo cross-validation was used to evaluate the network performance, with 85 subjects in each trial reserved for model training, 5 for validation, and 10 for testing. Image segmentation and quantification metrics were evaluated on the test folds with respect to manual segmentations by a nuclear medicine physician, and compared to inter-rater agreement. The model's segmentation performance was also evaluated on a separate set of 19 images with high tumor load. RESULTS: With our best model, the lowest mean Dice coefficient on the test set was 0.826 for the sublingual gland, and the highest was 0.964 for liver. The highest mean error in tracer uptake quantification was 13.9% in the sublingual gland. Self-supervised pretraining improved training convergence, train-to-test generalization, and segmentation quality. In addition, we found that a multi-target network produced significantly higher segmentation accuracy than single-organ networks. CONCLUSIONS: The developed network can be used to automatically obtain high-quality organ segmentations for PSMA image analysis tasks. It can be used to reproducibly extract imaging data, and holds promise for clinical applications such as personalized radiation dosimetry and improved radioligand therapy.

Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging.

Prostate cancer is the second most common cause of malignancy among men, with bone metastasis being a significant source of morbidity and mortality in advanced cases. Detecting and treating bone metastasis at an early stage is crucial to improve the quality of life and survival of prostate cancer patients. This objective strongly relies on imaging studies. While CT and MRI have their specific utilities, they also possess certain drawbacks. Bone scintigraphy, although cost-effective and widely available, presents high false-positive rates. The emergence of PET/CT and PET/MRI, with their ability to overcome the limitations of standard imaging methods, offers promising alternatives for the detection of bone metastasis. Various radiotracers targeting cell division activity or cancer-specific membrane proteins, as well as bone seeking agents, have been developed and tested. The use of positron-emitting isotopes such as fluorine-18 and gallium-68 for labeling allows for a reduced radiation dose and unaffected biological properties. Furthermore, the integration of artificial intelligence (AI) and radiomics techniques in medical imaging has shown significant advancements in reducing interobserver variability, improving accuracy, and saving time. This article provides an overview of the advantages and limitations of bone scan using SPECT and SPECT/CT and PET imaging methods with different radiopharmaceuticals and highlights recent developments in hybrid scanners, AI, and radiomics for the identification of prostate cancer bone metastasis using molecular imaging.

Differential privacy preserved federated transfer learning for multi-institutional 68Ga-PET image artefact detection and disentanglement.

PURPOSE: Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (68Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images. METHODS: Altogether, 1413 patients with 68Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients' images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC). RESULTS: The three approaches investigated in this study for 68Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (CI 95%: 0.38 to 0.47), 0.32 ± 0.23 (CI 95%: 0.27 to 0.37) and 0.28 ± 0.15 (CI 95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (p-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in 68Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in 68Ga-PET imaging. CONCLUSION: The proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in 68Ga-PET imaging. This technique could be integrated in the clinic for 68Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.

Head-to-Head Comparison of CZT-SPECT and SPECT/CT Myocardial Perfusion Imaging: Interobserver and Intraobserver Agreement and Diagnostic Performance.

BACKGROUND: Myocardial perfusion imaging (MPI) plays a crucial role in diagnosing coronary artery disease (CAD), with single-photon emission computed tomography (SPECT) being a widely accepted method. The accuracy of MPI relies on image quality and the expertise of physicians. While CZT-SPECT cameras offer advantages, they can be susceptible to attenuation artifacts. Therefore, our objective was to evaluate the diagnostic accuracy of CZT-SPECT and SPECT/CT in a clinical setting. METHOD: We conducted a prospective single-center study involving patients with known or suspected stable ischemic heart disease who underwent SPECT-MPI using CZT-SPECT and SPECT/CT scanners, and the latter was equipped with cardiofocal collimation. Experienced physicians performed analysis and reporting based on automated quantification and visual image interpretation. RESULTS: A total of 77 patients (32 women (41.6%) and 45 men (58.4%) with an average age of 71.9 ± 8.9 years) were included. The agreement between readers regarding the final conclusion based on imaging reporting using both devices was very high (Kappa 0.87-0.93). Per-vessel analysis revealed a trend suggesting that CZT-SPECT was superior to conventional SPECT/CT in terms of sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, although the difference did not reach statistical significance. CONCLUSION: Our study demonstrated that CZT-SPECT imaging offers comparable diagnostic accuracy, improved patient comfort, and eliminates CT-induced radiation compared to SPECT/CT. These findings suggest that cardiac CZT-SPECT imaging has the potential to become a valuable imaging modality in clinical practice.

Bipolar Androgen Therapy: When Excess Fuel Extinguishes the Fire.

Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through "Darwinian" treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.

Automatic segmentation of prostate cancer metastases in PSMA PET/CT images using deep neural networks with weighted batch-wise dice loss.

PURPOSE: Automatic and accurate segmentation of lesions in images of metastatic castration-resistant prostate cancer has the potential to enable personalized radiopharmaceutical therapy and advanced treatment response monitoring. The aim of this study is to develop a convolutional neural networks-based framework for fully-automated detection and segmentation of metastatic prostate cancer lesions in whole-body PET/CT images. METHODS: 525 whole-body PET/CT images of patients with metastatic prostate cancer were available for the study, acquired with the [18F]DCFPyL radiotracer that targets prostate-specific membrane antigen (PSMA). U-Net (1)-based convolutional neural networks (CNNs) were trained to identify lesions on paired axial PET/CT slices. Baseline models were trained using batch-wise dice loss, as well as the proposed weighted batch-wise dice loss (wDice), and the lesion detection performance was quantified, with a particular emphasis on lesion size, intensity, and location. We used 418 images for model training, 30 for model validation, and 77 for model testing. In addition, we allowed our model to take n = 0,2, …, 12 neighboring axial slices to examine how incorporating greater amounts of 3D context influences model performance. We selected the optimal number of neighboring axial slices that maximized the detection rate on the 30 validation images, and trained five neural networks with different architectures. RESULTS: Model performance was evaluated using the detection rate, Dice similarity coefficient (DSC) and sensitivity. We found that the proposed wDice loss significantly improved the lesion detection rate, lesion-wise DSC and lesion-wise sensitivity compared to the baseline, with corresponding average increases of 0.07 (p-value = 0.01), 0.03 (p-value = 0.01) and 0.04 (p-value = 0.01), respectively. The inclusion of the first two neighboring axial slices in the input likewise increased the detection rate by 0.17, lesion-wise DSC by 0.05, and lesion-wise mean sensitivity by 0.16. However, there was a minimal effect from including more distant neighboring slices. We ultimately chose to use a number of neighboring slices equal to 2 and the wDice loss function to train our final model. To evaluate the model's performance, we trained three models using identical hyperparameters on three different data splits. The results showed that, on average, the model was able to detect 80% of all testing lesions, with a detection rate of 93% for lesions with maximum standardized uptake values (SUVmax) greater than 5.0. In addition, the average median lesion-wise DSC was 0.51 and 0.60 for all the lesions and lesions with SUVmax>5.0, respectively, on the testing set. Four additional neural networks with different architectures were trained, and they both yielded stronger performance of segmenting lesions whose SUVmax>5.0 compared to the rest of lesions. CONCLUSION: Our results demonstrate that prostate cancer metastases in PSMA PET/CT images can be detected and segmented using CNNs. The segmentation performance strongly depends on the intensity, size, and the location of lesions, and can be improved by using specialized loss functions. Specifically, the models performed best in detection of lesions with SUVmax>5.0. Another challenge was to accurately segment lesions close to the bladder. Future work will focus on improving the detection of lesions with lower SUV values by designing custom loss functions that take into account the lesion intensity, using additional data augmentation techniques, and reducing the number of false lesions by developing methods to better separate signal from noise.

Outcome of patients with biochemical recurrence of prostate cancer after PSMA PET/CT-directed radiotherapy or surgery without systemic therapy.

BACKGROUND: Radiotherapy (RT) and surgery are potential treatment options in patients with biochemical recurrence (BCR) following primary prostate cancer treatment. This study examines the value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-informed surgery and RT in patients with BCR treated without systemic therapy. METHODS: This is a post-hoc subgroup analysis of a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer at initial curative-intent treatment, BCR after primary treatment with curative intent, having five or fewer lesions identified on [18F]DCFPyL PET/CT, and treatment with either PET/CT-directed RT or surgery without systemic therapy. The biochemical progression-free survival after PSMA ligand PET/CT-directed RT and surgery was determined. Uni- and multivariate Cox regression analyses were performed for the association of patients' characteristics, tumor-specific variables, and PSMA PET/CT imaging results with biochemical progression at the last follow-up. RESULTS: Fifty-eight patients (30 in surgery and 28 in radiotherapy groups) met the inclusion criteria. A total of 87 PSMA-positive lesions were detected: 16 local recurrences (18.4%), 54 regional lymph nodes (62.1%), 6 distant lymph nodes (6,8%), and 11 osseous lesions (12.7%). A total of 85.7% (24 of 28) and 70.0% (21 of 30) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after RT and surgery, respectively. At a median follow-up time of 21 months (range, 6-32 months), the median biochemical progression-free survival was 19 months (range, 4 to 23 months) in the radiotherapy group, as compared with 16.5 months (range, 4 to 28 months) in the surgery group. On multivariate Cox regression analysis, the number of PSMA positive lesions (2-5 lesions compared to one lesion), and the anatomic location of the detected lesions (distant metastasis vs. local relapse and pelvic nodal relapse) significantly correlated with biochemical progression at the last follow-up, whereas other clinical, tumor-specific, and imaging parameters did not. CONCLUSIONS: This study suggests that RT or surgery based on [18F]DCFPyL PET/CT are associated with high PSA response rates. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up. Further studies are needed to assess the impact of targeting these sites on patient relevant outcomes. TRIAL REGISTRATION: Registered September 14, 2016; NCT02899312; https://clinicaltrials.gov/ct2/show/NCT02899312.

Intra-individual comparison of 18F-sodium fluoride PET-CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial.

BACKGROUND: Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. METHODS: MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. FINDINGS: Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. INTERPRETATION: 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. FUNDING: Canadian Institutes of Health Research.

PSA-Stratified Performance of [18F]DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer Patients under Androgen Deprivation Therapy.

Based on in vitro studies, it is known that androgen deprivation therapy (ADT) increases prostate-specific membrane antigen (PSMA) expression on prostate cancer (PCa) cells. However, ADT also has cytoreductive effects which can decrease lesion size. The present evaluation was conducted to further analyze the influence of ongoing ADT on [18F]DCFPyL positron emission tomography/computed tomography (PET/CT) performance in the setting of biochemically recurrent PCa. We retrospectively evaluated two groups of PCa patients, previously treated with radical intent, who had undergone [18F]DCFPyL PET/CT because of biochemical relapse with a minimum PSA level of 0.4 ng/mL. One group consisted of 95 patients under ADT at the time of the PET examination, and the other consisted of 445 patients not receiving ADT at the time of PET/CT. The uptake characteristics of the cardiac blood pool, liver, parotid glands, and five most active lesions were measured and compared between these two groups. The overall detection rate of [18F]DCFPyL PET/CT in patients under ADT at the time of imaging was significantly higher than patients not under ADT (91.6% vs. 80.4%, p-value = 0.007). However, the PSA-stratified differences in detection rates between patients with and without ADT did not reach statistical significance. Except for the maximal standardized uptake values corrected for lean body mass (SULmax) in the PSA range of 1 to <2 ng/mL, the intensity and volume of [18F]DCFPyL accumulation were higher in patients with ADT compared to the patients without. Statistical significance was attained for the SULmax in PSA range of 0.5 to <1 ng/mL (p-value = 0.0004) and metabolic tumor volume (MTV) in all PSA ranges (p-values of 0.0005 to 0.03). No significant difference was observed for radiotracer uptake in normal organs between the two groups with and without ADT. In this study population with biochemical recurrence of PCa and measurable PSA, ongoing ADT at the time of [18F]DCFPyL PET/CT imaging was associated with higher radiotracer uptake and overall lesion detection rate. This could be due in part to the more aggressive disease phenotype in patients with ongoing ADT.

An Evolution of Reporting: Identifying the Missing Link.

In recent years, radiologic imaging has undergone tremendous technological advances and is now a pillar of diagnostic and treatment algorithms in clinical medicine. The increased complexity and volume of medical imaging has led clinicians to become ever more reliant on radiologists to both identify and interpret patient studies. A radiologist's report provides key insights into a patient's immediate state of health, information that is vital when choosing the most appropriate next steps in management. As errors in imaging interpretation or miscommunication of results can greatly impair patient care, identifying common error sources is vital to minimizing their occurrence. Although mistakes in medical imaging are practically inevitable, changes to the delivery of imaging reporting and the addition of artificial intelligence algorithms to analyze clinicians' communication skills can minimize the impact of these errors, keep up with the continuously evolving landscape of medical imaging, and ultimately close the communication gap.

Prognostic value of 2-[18F]FDG PET-CT in metastatic melanoma patients receiving immunotherapy.

PURPOSE: The 2-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) is used for the evaluation of response to immunotherapy in malignant melanoma. Here, we evaluated the prognostic value of various metabolic parameters in baseline and different time points after therapy. METHODS: In this retrospective study, 51 metastatic melanoma patients, who had received immunotherapy, were included. Patients with baseline and two follow-up 2-[18F]FDG PET/CT studies (3 and 6 months after therapy) were selected. Multiple metabolic parameters and tumor-to-background ratios (TBRs) were extracted and correlated with OS. RESULTS: The 3- and 5-year OS rates were 49% and 43.1%, respectively. On baseline 2-[18F]FDG PET/CT, only standardized uptake value corrected for lean body mass (SULmax and SULpeak), as well as most of the TBRs were predictive for 3- and 5-year OS rates. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and most of the TBRs were predictive on both follow-up studies. Also, the changes in values of MTV, TLG and most of the TBRs from the baseline to the 3-month and 6- month follow-up studies were prognostic. On multivariate analysis, all of the most predictive parameters for OS were derived from the 3-month follow-up study. The ratio of TBRmean to the mediastinum was the best factor (cutoff value of 2.15, sensitivity of 88.5% and specificity of 68.0% for 3-year survival). CONCLUSION: Metabolic parameters derived from 2-[18F]FDG PET/CT are valuable tools for the prediction of 3- and 5-year OS rates in metastatic melanoma patients undergoing immunotherapy. The 3-month follow-up 2-[18F]FDG PET/CT is of particular importance in this regard.

A Prospective Study on [68Ga]-PSMA PET/CT Imaging in Newly Diagnosed Intermediate- and High-Risk Prostate Cancer.

OBJECTIVES: Prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) is an emerging modality to detect metastatic disease in patients with prostate cancer (PCa). This prospective study aimed to evaluate the role of [68Ga]-PSMA PET/CT in the initial workup of intermediate and high-risk PCa. METHODS: Twenty-five patients with newly transrectal ultrasound biopsy-proven, untreated intermediate- and high-risk PCa (mean age, 68.5±6.2 years; range 55-83 years) were enrolled in this prospective study between September 2018 and June 2020 and underwent a [68Ga]-PSMA PET/CT examination. All images were analyzed both visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax) of the primary prostatic tumor and metastatic lesions. The diagnostic sensitivity of [68Ga]-PSMA PET/CT for the diagnosis of PCa was established by histopathology as the reference standard. The associations between SUVmax of the primary tumors and prostate-specific antigen (PSA) levels, Gleason scores (GSs), and metastatic extent of the disease were studied. RESULTS: All patients had a positive [68Ga]-PSMA PET/CT exam. Seventeen patients (58%) showed [68Ga]-PSMA avidity in both prostate lobes and 8 (32%) had unilateral uptake. SUVmax in the primary tumor significantly correlated with serum PSA values (r=0.57, P=0.003). PSMA PET/CT depicted regional lymph node metastases in 32% of patients, distant lymph node metastases in 20%, osseous metastases in 16% and pulmonary metastases in 8% of patients. Sixty percent of PSMA-positive bone metastases and 21.4% of intraprostatic tumoral lesions were missed on the contemporaneous bone scintigraphy and magnetic resonance imaging, respectively. CONCLUSION: [68Ga]-PSMA PET/CT shows promise as a valuable imaging modality with high diagnostic sensitivity in the setting of intermediate and high-risk PCa. Moreover, the SUVmax of the primary tumor has a positive correlation with PSA levels at the time of the scan.

Factors predicting biochemical response and survival benefits following radioligand therapy with [177Lu]Lu-PSMA in metastatic castrate-resistant prostate cancer: a review.

BACKGROUND: Prostate cancer (PC) is one of the most common cancers in men. Although the overall prognosis is favorable, the management of metastatic castration-resistant prostate cancer (mCRPC) patients is challenging. Usually, mCRPC patients with progressive disease are considered for radioligand therapy (RLT) after exhaustion of other standard treatments. The prostate-specific membrane antigen (PSMA) labeled with Lutetium-177 ([177Lu]Lu-PSMA) has been widely used, showing favorable and successful results in reducing prostate-specific antigen (PSA) levels, increasing quality of life, and decreasing pain, in a multitude of studies. Nevertheless, approximately thirty percent of patients do not respond to [177Lu]Lu-PSMA RLT. Here, we only reviewed and reported the evaluated factors and their impact on survival or biochemical response to treatment to have an overview of the potentialprognostic parameters in [177Lu]Lu-PSMA RLT. METHODS: Studies were retrieved by searching MEDLINE/PubMed and GoogleScholar. The search keywords were as follows: {("177Lu-PSMA") AND ("radioligand") AND ("prognosis") OR ("predict")}. Studies discussing one or more factors which may be prognostic or predictive of response to [177Lu]Lu-PSMA RLT, that is PSA response and survival parameters, were included. RESULTS: Several demographic, histological, biochemical, and imaging factors have been assessed as predictive parameters for the response to thistreatment; however, the evaluated factors were diverse, and the results mostly were divergent, except for the PSA level reduction after treatment, which unanimously predicted prolonged survival. CONCLUSION: Several studies have investigated a multitude of factors to detect those predicting response to [177Lu]Lu-PSMA RLT. The results wereinconsistent regarding some factors, and some were evaluated in only a few studies. Future prospective randomized trials are required to detect theindependent prognostic factors, and to further determine the clinical and survival benefits of [177Lu]Lu-PSMA RLT.

The Effects of Monosodium Glutamate on PSMA Radiotracer Uptake in Men with Recurrent Prostate Cancer: A Prospective, Randomized, Double-Blind, Placebo-Controlled Intraindividual Imaging Study.

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer. However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA-targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 patients with biochemically recurrent prostate cancer. Each subject served as his own control. PET/CT imaging sessions using 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were performed 3-7 d apart, after oral administration of either 12.7 g of MSG or placebo. Data from the 2 sets of images were analyzed by placing regions of interest on lacrimal, parotid, and submandibular glands; left ventricle; liver; spleen; kidneys; bowel; urinary bladder; gluteus muscle; and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the region-of-interest data. Results: In total, 142 pathologic lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in SUVmax corrected for lean body mass (SULmax) on images obtained after MSG administration in the parotids (24% ± 14%, P = 0.001), submandibular glands (35% ± 11%, P < 0.001), and kidneys (23% ± 26%, P = 0.014). Significant decreases were also observed in the lacrimal glands (49% ± 13%, P < 0.001), liver (15% ± 6%, P < 0.001), spleen (28% ± 13%, P = 0.001), and bowel (44% ± 13%, P < 0.001). A mildly lower blood pool SULmean was observed after MSG administration (decrease of 11% ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration than on the placebo studies (SULmax median decrease, 33%; range, -1% to 75%; P < 0.001). No significant adverse events occurred after placebo or MSG administration, and vital signs were stable. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney, and other normal-organ PSMA radiotracer uptake in human subjects, using 18F-DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

177Lu-EDTMP for Metastatic Bone Pain Palliation: A Systematic Review and Meta-Analysis.

Purpose: Painful metastatic bone involvement is common in advanced stages of many cancers. Between available radionuclides for bone pain palliation, no consensus has been reached on lutetium ethylenediaminetetramethylene phosphonate (177Lu-EDTMP) administration in this milieu. The aim of this study is to evaluate the treatment efficacy, safety profile, and toxicities of 177Lu-EDTMP in patients with metastatic bone involvement, according to the published literature. Methods: A comprehensive literature search of PubMed/MEDLINE, Scopus, and Google Scholar databases was carried out to retrieve pertinent articles published until January 2019, concerning the clinical efficacy and safety of 177Lu-EDTMP for bone pain palliative purposes. Results: Eight studies (172 patients) were included. This analysis revealed statistically significant effect of 177Lu-EDTMP therapy on the visual analog score (4.84% (95% CI: 3.88-5.81; p < 0.001), bone palliative pain response (84%, 95% CI: 75%-90%; p < 0.001), and Karnofsky performance status (21%, 95% CI: 18%-24%; p < 0.001) overall (as well as in the high-dose and low-dose subgroups). Complete palliative pain response to treatment was observed in 32% (95% CI: 16%-53%) of patients receiving 177Lu-EDTMP. Anemia was found to be the most common hematologic toxicity imposed by this therapeutic approach (grade I/II anemia in 24% (95% CI: 14%-38%; p < 0.001) and grade III/IV anemia in 19% (95% CI: 12%-28%; p < 0.001)). Conclusions: 177Lu-EDTMP seems to have comparable efficacy and safety profile as that of the frequently administered radiopharmaceuticals for bone palliation. Therefore, this agent can be a good option for bone pain palliative purposes, in case of limited access to other bone palliative radiopharmaceuticals.

68Ga-DOTATATE PET/CT Compared with 131I-MIBG SPECT/CT in the Evaluation of Neural Crest Tumors.

OBJECTIVES: 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) has shown promising results in imaging of neural crest tumors (NCT). Herein, we compared the performance of 68Ga-DOTATATE PET/CT and 131I-MIBG single photon emission computed tomography (SPECT)/CT in the initial diagnosis, staging and follow-up of patients with NCTs. METHODS: Twenty-five patients (males:females=8:17; age range=2-71 years) with clinically proven or suspicious neuroblastoma, pheochromocytoma (PCC) or paraganglioma (PGL) were enrolled in this prospective study and underwent both 68Ga-DOTATATE PET/CT and 131I-MIBG SPECT/CT. A composite reference standard derived from histopathological information, together with anatomical and functional imaging findings, was used to validate the results. Imaging findings were assessed on a per-patient and on a per-lesion basis. Sensitivity and accuracy were assessed using McNemar's test. RESULTS: Referring to radiological imaging and histopathological findings as reference standard, 68Ga-DOTATATE and 131I-MIBG scans showed a sensitivity and accuracy of (100%, 96%) and (86.7%, 88%), respectively, on a per-patient basis. In PCC/PGL patients, on a per-patient basis, the sensitivity of 68Ga-DOTATATE was 100% and that of 131I-MIBG was 77.8%. In neuroblastoma patients, on a per-patient basis, the sensitivities of both 68Ga-DOTATATE and 131I-MIBG were 100%. Overall, in this patient cohort, 68Ga-DOTATATE PET/CT identified 52 lesions and 131I-MIBG SPECT/CT identified only 30 lesions. On a per-lesion analysis, 68Ga-DOTATATE was found to be superior to 131I-MIBG in detecting lesions in all anatomical locations, particularly osseous lesions. According to the McNemar test results, differences were not statistically significant. CONCLUSION: This relatively small patient cohort suggests 68Ga-DOTATATE PET/CT be superior to 131I-MIBG SPECT/CT in providing particularly valuable information for both primary staging and follow-up in patients with NCT.

Imaging review of ocular and optic nerve trauma.

Traumatic ocular injuries account for a substantial number of emergency department visits annually and represent a significant source of patient disability. A thorough understanding of ocular/optic nerve anatomy and traumatic pathology is fundamental in the accurate and efficient interpretation of emergency neuroradiology. This article will review relevant anatomy, imaging protocols, clinical symptomatology, and key imaging findings associated with the broad spectrum of traumatic ocular and optic nerve pathology.