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RationaleThe development of consensus guidelines for interpretation of Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) is needed to provide more consistent reports in clinical practice. The standardization of PSMA-PET interpretation may also contribute to increasing the data reproducibility within clinical trials. Finally, guidelines in PSMA-PET interpretation are needed to communicate the exact location of findings to referring physicians, to support clinician therapeutic management decisions.MethodsA panel of worldwide experts in PSMA-PET was established. Panelists were selected based on their expertise and publication record in the diagnosis or treatment of PCa, in their involvement in clinical guidelines and according to their expertise in the clinical application of radiolabeled PSMA inhibitors. Panelists were actively involved in all stages of a modified, nonanonymous, Delphi consensus process.ResultsAccording to the findings obtained by modified Delphi consensus process, panelist recommendations were implemented in a structured report for PSMA-PET.ConclusionsThe E-PSMA standardized reporting guidelines, a document supported by the European Association of Nuclear Medicine (EANM), provide consensus statements among a panel of experts in PSMA-PET imaging, to develop a structured report for PSMA-PET in prostate cancer and to harmonize diagnostic interpretation criteria.

Chimeric antigen receptor (CAR) T-cell therapy is one of the most remarkable advances in cancer therapy in the last several decades. More than 300 adoptive T-cell therapy trials are ongoing, which is a testament to the early success and hope engendered by this line of investigation. Despite the enthusiasm, application of CAR T-cell therapy to solid tumours has had little success, although positive outcomes are increasingly being reported for these diseases. In this Series paper, we discuss the short-term strategies to improve CAR T-cell therapy responses, particularly for solid tumours, by combining CAR T-cell therapy with radiotherapy through the use of careful monitoring and non-invasive imaging. Through the use of imaging, we can gain greater mechanistic insights into the cascade of events that must unfold to enable tumour eradication by CAR T-cell therapy.

Background The rapidly expanding clinical adaptation of prostate-specific membrane antigen (PSMA)-targeted PET imaging in the evaluation of patients with prostate cancer has placed an increasing onus on understanding both the potential pearls of interpretation as well as limitations of this new technique. As with any new molecular imaging modality, accurate characterization of abnormalities on PSMA-targeted PET imaging can be accomplished only if one is aware of the normal distribution pattern, physiological variants of radiotracer uptake, and potential sources of false-positive and false-negative imaging findings. In recent years, a growing number of reports have come to light describing incidental non-prostatic benign or malignant pathologies with high uptake on PSMA-targeted PET imaging. In this review, we have summarized the published literature regarding the potential pearls and technical and interpretive pitfalls of this imaging modality. Knowledge of these limitations can increase the confidence of interpreting physicians and thus improve patient care. Conclusions As PSMA-targeted PET is expected to be evaluated in larger prospective trials, the dissemination of potential diagnostic pitfalls and the biologic underpinning of those findings will be of increased importance.

Purpose Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [ 18 F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer. Procedures Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM. Results No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUV max up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [ 18 F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi). Conclusions [ 18 F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [ 18 F]DCFPyL is similar to that from other PET radiotracers.

The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measure-ment of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, ex-pansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high- throughput methods to discover and optimize affinity agents to key cellular tar-gets, new ways to manipulate genetic material, and expanded use of cloud com-puting. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full- blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging- particularly when combined with liquid biopsy for screening purposes- promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecu-lar imaging can be undertaken, the tools used and under development, and near- term challenges and opportunities in oncology.

PurposeThis meta-analysis aims to establish the diagnostic performance of 18F-NaF-PET/CT for the detection of bone metastases in prostate cancer patients. The performance of 18F-NaF-PET/CT was compared with other imaging techniques in the same cohort of patients.MethodsA systematic search was performed in PubMed/Medline and EMBASE (last Updated, September 28, 2018). Studies with histopathology confirmation and/or clinical/imaging follow-up as reference standard were eligible for inclusion.ResultsA total of 14 studies were included. Twelve studies including 507 patients provided per-patient basis information. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristics curve (AUC) of 18F-NaF-PET/CT for the detection of bone metastases were 0.98 (95% CI 0.95–0.99), 0.90 (95% CI 0.86–0.93), 123.2 and 0.97, respectively. Seven studies provided the lesion-based accuracy information of 1812 lesions identified on 18F-NaF-PET/CT with the pooled sensitivity, specificity, DOR and AUC of 0.97 (95% CI 0.95–0.98), 0.84 (95% CI 0.81–0.87), 206.8 and 0.97, respectively. The overall diagnostic performance of 18F-NaF-PET/CT is superior to 99mTc-bone scintigraphy (AUC 0.842; P < 0.001; four studies) and 99mTc-SPECT (AUC 0.896; P < 0.001, four studies). Compared to 18F NaF-PET/CT, whole-body MRI with diffusion-weighted imaging (DWI) was shown to have lower sensitivity (0.83, 95% CI 0.68–0.93), with no significant difference in the overall performance (AUC 0.947; P = 0.18, four studies).Conclusion18F-NaF-PET/CT has excellent diagnostic performance in the detection of bone metastases in staging and restaging of high-risk prostate cancer patients. The performance of 18F-NaF-PET/CT is superior to 99mTc bone scintigraphy and SPECT, and comparable to DWI–MRI.

BackgroundDiagnosis of Parkinson’s disease (PD) is informed by the presence of progressive motor and non-motor symptoms and by imaging dopamine transporter with [123I]ioflupane (DaTscan). Deep learning and ensemble methods have recently shown promise in medical image analysis. Therefore, this study aimed to develop a three-stage, deep learning, ensemble approach for prognosis in patients with PD.MethodsRetrospective data of 198 patients with PD were retrieved from the Parkinson’s Progression Markers Initiative database and randomly partitioned into the training, validation, and test sets with 118, 40, and 40 patients, respectively. The first and second stages of the approach extracted features from DaTscan and clinical measures of motor symptoms, respectively. The third stage trained an ensemble of deep neural networks on different subsets of the extracted features to predict patient outcome 4 years after initial baseline screening. The approach was evaluated by assessing mean absolute percentage error (MAPE), mean absolute error (MAE), Pearson’s correlation coefficient, and bias between the predicted and observed motor outcome scores. The approach was compared to individual networks given different data subsets as inputs.ResultsThe ensemble approach yielded a MAPE of 18.36%, MAE of 4.70, a Pearson’s correlation coefficient of 0.84, and had no significant bias indicating accurate outcome prediction. The approach outperformed individual networks not given DaTscan imaging or clinical measures of motor symptoms as inputs, respectively.ConclusionThe approach showed promise for longitudinal prognostication in PD and demonstrated the synergy of imaging and non-imaging information for the prediction task.

Stem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n = 1), rats (n = 4), rabbits (n = 4) and non-human primates (n = 3), via carotid artery in rats (n = 4) and non-human primates (n = 3), and via intra-myocardial injection in rats (n = 5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.

Objective Molecular imaging with positron emission tomography (PET) provides a powerful means of identifying and characterizing cancerous processes, as well as providing a quantitative framework within which response to therapy can be ascertained. Unfortunately, the most commonly used PET radiotracer, 18 F-fluorodeoxyglucose (FDG), has not demonstrated a definitive role in determining response to therapy in metastatic renal cell carcinoma (RCC). As a result, new radiotracers able to reliably image RCC could be of tremendous value for this purpose. Methods Five patients with known metastatic RCC were imaged with the low-molecular weight radiotracer 18 F-DCFPyL, an inhibitor of the prostate-specific membrane antigen at 60 min post injection. 18 F-DCFPyL PET/CT and conventional images (either contrast-enhanced computed tomography or magnetic resonance imaging) were centrally reviewed for suspected sites of disease. Results In all five patients imaged, sites of putative metastatic disease were readily identifiable by abnormal 18 F-DCFPyL uptake, with overall more lesions detected than on conventional imaging. These PET-detected sites included lymph nodes, pancreatic parenchymal lesions, lung parenchymal lesions, a brain parenchymal lesion, and other soft tissue sites. 18 F-DCFPyL uptake ranged from subtle to intense with maximum standardized uptake values (SUV max ) for the identified lesions of 1.6–19.3. Based upon this small patient series, limited pathology and imaging follow-up of these patients suggests a higher sensitivity for 18 F-DCFPyL compared to conventional imaging in the detection of metastatic RCC (94.7 versus 78.9 %). Conclusions PSMA expression in the tumor neovasculature of RCC has been previously established and is believed to provide the basis for the imaging findings presented here. PSMA-based PET/CT with radiotracers such as 18 F-DCFPyL may allow more accurate staging of patients with RCC and conceivably the ability to predict and follow therapy in patients treated with agents targeting the neovasculature.

Adenoid cystic carcinoma (ACC) is a rare malignancy of the salivary glands with poor long-term outcomes and with a need for improved imaging and therapeutic options. Prostate-specific membrane antigen (PSMA) expression has been observed in ACC and preliminary studies have demonstrated PET imaging using 68 Ga-functionalized PSMA agents for positron emission tomography (PET). We aimed to assess the extent of PSMA expression in a collection of archival ACC samples and demonstrate the feasibility of using  18 F-DCFPyL for PSMA PET imaging of ACC. PSMA expression levels were assessed in 77 ACC and 11 unaffected parotid gland control samples by immunohistochemistry and quantified by mean H-score. Three patients with metastatic ACC, who had previously undergone local resection, were imaged with 18 F-DCFPyL PSMA PET in a prospective, pilot trial setting. Demographic, oncologic, and treatment history from the PET patient cohort were acquired at the time of imaging. Maximum standardized uptake values (SUV max ) were obtained from representative presumptive metastatic lesions on the  18 F-DCFPyL scans by manual placement of regions-of-interest. PSMA expression was detected in 52% of archival ACC samples, compared to 18% in the unaffected salivary glands. Moderate or high levels of PSMA expression (H-score > 5) were seen in 37% of samples. Radiotracer avid disease was identified on PET imaging of all three patients with tumor SUV max values of 4.1, 4.0, and 2.0, corresponding to tumor-to-liver ratios of 0.7, 1.0, and 0.4 respectively. We find that PSMA is expressed in a majority of histologic samples from patients with ACC. We also demonstrated the feasibility of  18 F-DCFPyL PSMA-targeted PET imaging in the assessment of ACC. Overall, the tumor uptake on  18 F-DCFPyL PET was modest compared to lesional uptake seen in prostate cancer. Given the potential role of PSMA-targeted agents in the management of ACC, broadening access to PSMA PET through F-18-labeled PSMA PET agents is important. Clinical trials investigating the use of PSMA-targeted radioligand therapies for ACC are underway.