Detection of Biochemically Recurrent Prostate Cancer with [18F]DCFPyL PET/CT: An Updated Systematic Review and Meta-Analysis with a Focus on Correlations with Serum Prostate-Specific Antigen Parameters.

[18F]DCFPyL is increasingly used for prostate-specific membrane antigen (PSMA) mediated imaging of men with biochemically recurrent prostate cancer (BRPCa). In this meta-analysis, which is updated with the addition of multiple new studies, including the definitive phase III CONDOR trial, we discuss the detection efficiency of [18F]DCFPyL in BRPCa patients. PubMed was searched on 29 September 2022. Studies evaluating the diagnostic performance of [18F]DCFPyL among patients with BRPCa were included. The overall pooled detection rate with a 95% confidence interval (95% CI) was calculated among all included studies and stratified among patients with PSA ≥ 2 vs. <2 ng/mL and with PSA ≥ 0.5 vs. <0.5 ng/mL. The association of detection efficiency with pooled PSA doubling time from two studies was calculated. Seventeen manuscripts, including 2252 patients, met the inclusion criteria and were used for data extraction. A previous meta-analysis reported that the pooled detection rate was 0.81 (95% CI: 0.77-0.85), while our study showed a pooled overall detection rate of 0.73 (95% CI: 0.66-0.79). An increased proportion of positive scans were found in patients with PSA ≥ 2 vs. <2 ng/mL and PSA ≥ 0.5 vs. <0.5 ng/mL. No significant difference was found in detection efficiency between those with PSA doubling time ≥ 12 vs. <12 months. Detection efficiency is statistically related to serum PSA levels but not to PSA doubling time based on available data. The detection efficiency of [18F]DCFPyL in men with BRPCa has trended down since a previous meta-analysis, which may reflect increasingly stringent inclusion criteria for studies over time.

Assessment of anti-GAD65-associated cerebellar ataxia with 18F-FDG cerebellar uptake: ROC analysis.

OBJECTIVE: Anti-glutamic acid decarboxylase 65 (anti-GAD65)-associated neurological disorders include two major phenotypes, namely Stiff person syndrome (SPS) and cerebellar ataxia (CA). Considering the potential for better outcomes with prompt immunotherapy, early detection of CA is crucial. Hence, a non-invasive imaging biomarker to detect CA with high specificity is desired. Herein, we evaluated brain 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) PET in detecting CA based on cerebellar uptake using receiver operating characteristic (ROC) analysis and five-fold cross-validation. METHODS: This study was based on STARD 2015 guidelines: thirty patients with anti-GAD65-associated neurological disorders, 11 of whom with CA were studied. Five test sets were created after patients were randomly sorted and divided into 5 equal folds. Each iteration included 24 patients for ROC analysis and 6 patients reserved for testing. The Z scores of left cerebellum, vermis, right cerebellum, and the average of the three regions were used in ROC analysis to determine areas with significant area under the curve (AUC). The cut-off values with high specificity were determined among the 24 patients in each iteration and tested against the reserved 6 patients. RESULTS: Left cerebellum and average of the three regions showed significant AUC above 0.5 in all iterations with left cerebellum being the highest AUC in 4 iterations. Testing the cut-off values of the left cerebellum against the reserved 6 patients in each iteration showed 100% specificity with sensitivities ranging from 0 to 75%. CONCLUSIONS: Cerebellar 18F-FDG PET uptake can differentiate CA phenotypes from patients with SPS with high specificity.

Comparison of quantitative FDG-PET and MRI in anti-LGI1 autoimmune encephalitis.

OBJECTIVES: Anti-leucine glioma-inactivated protein 1 (anti-LGI1) autoimmune encephalitis (AE) presents as subacute memory loss, behavioral changes, and seizures. Diagnosis and treatment delays can result in long term sequelae, including cognitive impairment. 18F-FDG PET/CT may be more sensitive than MRI in patients with AE. Our objective was to determine if anti-LGI1 is associated with a distinct pattern of FDG uptake and whether this pattern persists following treatment. METHODS: Nineteen18F-FDG PET/CT brain scans (13 pre-treatment, 6 convalescent phase) for 13 patients with anti-LGI1 were studied using NeuroQ™ and CortexID™. The sensitivity of the PET images was compared to MRI. The Z scores of 47 brain regions between the pre-treatment and next available follow-up images during convalescence were compared. RESULTS: All 18F-FDG PET/CT scans demonstrated abnormal FDG uptake, while only 6 (42.9%) pre-treatment brain MRIs were abnormal. The pre-treatment scans demonstrated hypermetabolism in the bilateral medial temporal cortices, basal ganglia, brain stem, and cerebellum and hypometabolism in bilateral medial and mid frontal, cingulate, and parietotemporal cortices. Overall, the brain uptake during convalescence showed improvement of the Z scores towards 0 or normalization of previous hypometabolic activity in medial frontal cortex, inferior frontal cortex, Broca's region, parietotemporal cortex, and posterior cingulate cortex and previous hypermetabolic activity in medial temporal cortices, caudate, midbrain, pons and cerebellum. CONCLUSIONS: Brain FDG uptake was more commonly abnormal than MRI in the pre-treatment phase of anti-LGI1, and patterns of dysmetabolism differed in the pre-treatment and convalescent phases. These findings may expedite the diagnosis, treatment, and monitoring of anti-LGI1 patients.

Deep learning and radiomics framework for PSMA-RADS classification of prostate cancer on PSMA PET.

BACKGROUND: Accurate classification of sites of interest on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) images is an important diagnostic requirement for the differentiation of prostate cancer (PCa) from foci of physiologic uptake. We developed a deep learning and radiomics framework to perform lesion-level and patient-level classification on PSMA PET images of patients with PCa. METHODS: This was an IRB-approved, HIPAA-compliant, retrospective study. Lesions on [18F]DCFPyL PET/CT scans were assigned to PSMA reporting and data system (PSMA-RADS) categories and randomly partitioned into training, validation, and test sets. The framework extracted image features, radiomic features, and tissue type information from a cropped PET image slice containing a lesion and performed PSMA-RADS and PCa classification. Performance was evaluated by assessing the area under the receiver operating characteristic curve (AUROC). A t-distributed stochastic neighbor embedding (t-SNE) analysis was performed. Confidence and probability scores were measured. Statistical significance was determined using a two-tailed t test. RESULTS: PSMA PET scans from 267 men with PCa had 3794 lesions assigned to PSMA-RADS categories. The framework yielded AUROC values of 0.87 and 0.90 for lesion-level and patient-level PSMA-RADS classification, respectively, on the test set. The framework yielded AUROC values of 0.92 and 0.85 for lesion-level and patient-level PCa classification, respectively, on the test set. A t-SNE analysis revealed learned relationships between the PSMA-RADS categories and disease findings. Mean confidence scores reflected the expected accuracy and were significantly higher for correct predictions than for incorrect predictions (P < 0.05). Measured probability scores reflected the likelihood of PCa consistent with the PSMA-RADS framework. CONCLUSION: The framework provided lesion-level and patient-level PSMA-RADS and PCa classification on PSMA PET images. The framework was interpretable and provided confidence and probability scores that may assist physicians in making more informed clinical decisions.

177 Lu-PSMA radioligand therapy effectiveness in metastatic castration-resistant prostate cancer: An updated systematic review and meta-analysis.

BACKGROUND: An updated systematic review and meta-analysis of relevant studies to evaluate the effectiveness of prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) in castration resistant prostate cancer (CRPC). METHODS: A systematic search was performed in July 2020 using PubMed/Medline database to update our prior systematic review. The search was limited to papers published from 2019 to June 2020. A total of 472 papers were reviewed. The studied parameters included pooled proportion of patients showing any or ≥50% prostate-specific antigen (PSA) decline after PRLT. Survival effects of PRLT were assessed based on pooled hazard ratios (HRs) of the overall survival (OS) according to any PSA as well as ≥50% PSA decline after PRLT. Response to therapy based on ≥50% PSA decrease after PRLT versus controls was evaluated using Mantel-Haenszel random effect meta-analysis. All p values < 0.05 were considered as statistically significant. RESULTS: A total of 45 publications were added to the prior 24 studies. 69 papers with total of 4157 patients were included for meta-analysis. Meta-analysis of the two recent randomized controlled trials showed that patients treated with 177 Lu-PSMA 617 had a significantly higher response to therapy compared to controls based on ≥50% PSA decrease. Meta-analysis of the HRs of OS according to any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. CONCLUSIONS: PRLT results in higher proportion of patients responding to therapy based on ≥50% PSA decline compared to controls. Any PSA decline and ≥50% PSA decline showed survival prolongation after PRLT. ADVANCES IN KNOWLEDGE: This is the first meta-analysis to aggregate the recent randomized controlled trials of PRLT which shows CRPC patients had a higher response to therapy after PRLT compared to controls.

Imaging of Cancer Immunotherapy: Response Assessment Methods, Atypical Response Patterns, and Immune-Related Adverse Events, From the AJR Special Series on Imaging of Inflammation.

The introduction of immunotherapy with immune-checkpoint inhibitors (ICIs) has revolutionized cancer treatment paradigms. Since FDA approval of the first ICI in 2011, multiple additional ICIs have been approved and granted marketing authorization, and many promising agents are in early clinical adoption. Due to the distinctive biologic mechanisms of ICIs, the patterns of tumor response and progression seen with immunotherapy differ from those observed with cytotoxic chemothera-pies. With increasing clinical adoption of immunotherapy, it is critical for radiologists to recognize different response patterns and common pitfalls to avoid misinterpretation of imaging studies or prompt premature cessation of potentially effective treatment. This review provides an overview of ICIs and their mechanisms of action and discusses anatomic and metabolic immune-related response assessment methods, typical and atypical patterns of immunotherapy response (including pseudoprogression, hyperprogression, dissociated response, and durable response), and common imaging features of immune-related adverse events. Future multicenter trials are needed to validate the proposed immune-related response criteria and identify the functional imaging markers of early treatment response and survival.

Brain and Muscle Metabolic Changes by FDG-PET in Stiff Person Syndrome Spectrum Disorders.

Objective: To report clinical characteristics and fluorodeoxyglucose positron emission tomography (FDG-PET) findings in the brain and muscles of individuals with stiff person syndrome (SPS) spectrum disorders (SPSSDs). Methods: Retrospective cohort study from 1997 to 2018 at Johns Hopkins Hospital identified 170 individuals with SPS or cerebellar ataxia (CA) associated with anti-glutamic acid decarboxylase (anti-GAD)-65 antibodies. Fifty-one underwent FDG-PET, with 50 involving the body and 30 with dedicated brain acquisition. The clinical and immunological profiles were extracted via medical record review. The brain scans were analyzed quantitatively using the NeuroQ software, with comparison with an averaged normal database. The body scans were reviewed qualitatively by a blinded nuclear medicine radiologist. Results: Mean age of symptom onset was 41.5 years (range 12-75 years). Majority were female (68%) and White (64%). Of the patients, 82% had SPS (majority being classic phenotype), and 18% had CA. Three had a paraneoplastic process. Forty-seven had serum anti-GAD, two with anti-amphiphysin, and one with anti-glycine receptor antibodies. Brain metabolic abnormalities were seen in both SPS and CA, with significant differences between the groups noted in the right superior frontal cortex, right sensorimotor cortex, left inferior parietal cortex, bilateral thalami, vermis, and left cerebellum. Of the patients, 62% demonstrated muscle hypermetabolism, most commonly bilateral, involving the upper extremities or axial muscles. Neither brain nor muscle metabolism was correlated with functional outcomes nor treatments. Conclusions: Metabolic changes as seen by FDG-PET are present in the brain and muscle in many individuals with SPSSD. Future studies are needed to assess whether FDG-PET can help aid in the diagnosis and/or monitoring of individuals with SPSSD.

Applications of artificial intelligence in oncologic 18F-FDG PET/CT imaging: a systematic review.

Artificial intelligence (AI) is a growing field of research that is emerging as a promising adjunct to assist physicians in detection and management of patients with cancer. 18F-FDG PET imaging helps physicians in detection and management of patients with cancer. In this study we discuss the possible applications of AI in 18F-FDG PET imaging based on the published studies. A systematic literature review was performed in PubMed on early August 2020 to find the relevant studies. A total of 65 studies were available for review against the inclusion criteria which included studies that developed an AI model based on 18F-FDG PET data in cancer to diagnose, differentiate, delineate, stage, assess response to therapy, determine prognosis, or improve image quality. Thirty-two studies met the inclusion criteria and are discussed in this review. The majority of studies are related to lung cancer. Other studied cancers included breast cancer, cervical cancer, head and neck cancer, lymphoma, pancreatic cancer, and sarcoma. All studies were based on human patients except for one which was performed on rats. According to the included studies, machine learning (ML) models can help in detection, differentiation from benign lesions, segmentation, staging, response assessment, and prognosis determination. Despite the potential benefits of AI in cancer imaging and management, the routine implementation of AI-based models and 18F-FDG PET-derived radiomics in clinical practice is limited at least partially due to lack of standardized, reproducible, generalizable, and precise techniques.

Neuroendocrine Tumor Theranostics: An Update and Emerging Applications in Clinical Practice.

OBJECTIVE. Theranostics have shown great promise for delivering precision medicine, particularly in neuroendocrine tumors (NETs). The clinical applications of radiolabeled somatostatin analogues in imaging and radionuclide therapy have been rapidly increasing over the past 2 decades and are currently integrated into the management guidelines of NETs. This article summarizes the available literature on different somatostatin receptor-targeting radiopharmaceuticals with theranostic potential in NETs, pheochromocytomas, and paragangliomas. We discuss the clinical application, administration, and toxicity of recent FDA-approved radionuclide therapies, including 177Lu-DOTATATE in advanced gastroenteropancreatic NETs and 131I-MIBG in advanced paragangliomas and pheochromocytomas. CONCLUSION. Several studies support the safety and clinical efficacy of peptide receptor radionuclide therapies in disease control and quality-of-life improvement in patients with NETs and report potential benefits of combined radionuclide treatment approaches. The utility and pitfalls of functional imaging in therapy response assessment and surveillance of NETs remain to be established.

A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177-labeled Prostate-specific Membrane Antigen-targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer.

CONTEXT: Castration-resistant prostate cancer (CRPC) treatment is an evolving challenge. Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) with small-molecule, urea-based agents labeled with the ß-particle-emitting radionuclide lutetium-177 (177Lu) is a promising new approach. OBJECTIVE: In this systematic review and meta-analysis, we evaluated the efficacy and toxicity of PRLT. EVIDENCE ACQUISITION: A systematic search was performed in PubMed/Medline (last updated February 18, 2019). A total of 250 studies were reviewed, and 24 studies with 1192 patients were included in the analysis. Proportions of patients with ≥50% serum prostate-specific antigen (PSA) decrease, any PSA decrease, and any PSA increase were extracted. Proportions of patients showing any grade toxicity and those with grade 3/4 toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) grading were extracted from manuscripts. Overall survival and progression-free survival were evaluated. A meta-analysis of single proportions was carried out. Furthermore, we compared the two most common PRLT agents, 177Lu-PSMA with 177Lu-PSMA-I&T, for effectiveness and toxicity. EVIDENCE SYNTHESIS: Among the 24 included studies, 20 included data on 177Lu-PSMA-617, three included data on 177Lu-PSMA-I&T, and one study had aggregated data for 177Lu-PSMA-617 and 177Lu-PSMA-I&T. The estimated proportion of 177Lu-PSMA-617-treated patients who showed a serum PSA decrease of ≥50% with at least an 8-wk interval between therapy and PSA measurement was 0.44 (0.39; 0.50). Therapy with 177Lu-PSMA-I&T demonstrated an estimated proportion of patients with ≥50% PSA reduction to be 0.36 (0.26; 0.47). The aggregate results for men treated with more than one cycle of any kind of PRLT showed an estimated proportion of 0.46 (0.41; 0.51) for PSA response ≥50%. Regarding aggregate data from all of the PRLT agents, we found that grade 3 and 4 toxicities were uncommon, with estimated proportions from 0.01 (0.00;0.04) for nausea, fatigue, diarrhea, and elevated aspartate transaminase up to 0.08 (0.05; 0.12) for anemia. There was considerable heterogeneity among the studies in the "any-grade toxicity" groups. Meta-regression showed that more than one cycle of PRLT is associated with a greater proportion of patients with ≥50% PSA reduction. Overall survival according to pooled hazard ratios (HRs) for any PSA decline was 0.29 (0.18; 0.46), and for >50% PSA reduction was 0.67 (0.43; 1.07). Progression-free survival according to a pooled HR of >50% PSA reduction was 0.53 (0.32; 0.86). CONCLUSIONS: The relatively high number of PSA responders alongside the low rate of severe toxicity reflects the potentially promising role of PRLT in treating CRPC. The ultimate utility of this treatment modality will become clearer as multiple prospective studies continue to accrue. In the interim, this systematic review and meta-analysis can serve as a compendium of effectiveness and adverse events associated with PRLT for treating clinicians. PATIENT SUMMARY: Prostate-specific membrane antigen-targeted endoradiotherapy/radioligand therapy (PRLT) is associated with ≥50% reduction in prostate-specific antigen level in a large number of patients and a low rate of toxicity, reflecting its potential in treating castration-resistant prostate cancer. This systematic review and meta-analysis presents as a compendium of the effectiveness and adverse events related to PRLT for treating clinicians.

Cellular and Molecular Imaging with SPECT and PET in Brain Tumors.

This review highlights the 2 major molecular imaging modalities that are used in clinics, namely single-photon emission computed tomography (SPECT) and positron emission tomography (PET), and their added value in management of patients with brain tumors. There are a variety of SPECT and PET radiotracers that can allow imaging of different molecular processes. Those radiotracers target specific molecular features of tumors, resulting in improved specificity of these agents. Potential applications include staging of brain tumors and evaluating post-therapeutic changes.

Traumatic lumbar spine fractures: Transverse process fractures dominate.

PURPOSE: With motor vehicle collisions (MVC) predominating as a source of trauma now, we sought to 1) reassess the types of traumatic lumbar spine fractures, 2) highlight the coincidence of transverse process fractures (TPF) with visceral injuries and 3) emphasize the difference in management between compression fracture (CF) and TPF. METHODS: We retrospectively reviewed the reports of lumbar spine and abdominopelvic CT scans from 2017 and 2018 to classify the types of spine fractures, their mechanism of injury, treatment and coexistence of abdominopelvic injuries. RESULTS: 2.2% of patients had posttraumatic lumbar spine fractures (113/5229), including 58 patients (51.3%) with isolated TPF and 42 (37.2%) with isolated CF; 13 patients had mixed types. TPF accounted for 70% of all fractures (195/277) as opposed to 24% for CF (67/277). MVC was responsible for 60.3% (35/58) of TPF but falls accounted for 73.8% (31/42) of CF. The odds ratio of having isolated TPF from MVC was 4.1[1.8-9.0] versus CF after a fall from standing was 4.5[2.0-10.5]. Of patients with both visceral injuries and lumbar spine fractures, 75% (27/36) had isolated TPF (odds ratio of visceral injury with TPF was 4.4[1.8-10.7]). No TPF were treated with an intervention, however 77% (40/52) of CF were addressed surgically or with braces. CONCLUSION: TPF are the most common lumbar spine fractures and are often associated with MVC. There is a high association between TPF and abdominopelvic visceral injury requiring radiologists' attentiveness even though the TPF is not directly addressed.

Effectiveness of Three-Dimensionally Printed Models in Anatomy Education for Medical Students and Resident Physicians: Systematic Review and Meta-Analysis.

INTRODUCTION: Despite a surge in the use of three-dimensional printing (3DP) in medical education, a comprehensive evaluation of randomized trials in its effectiveness is lacking. Radiologic studies play an integral role in affording educators the ability to create customized realistic anatomic models. This systematic review and meta-analysis sought to assess the effect of 3DP versus traditional 2-D methods for anatomy education. METHODS: PubMed, Scopus, Cochrane Library, ERIC, and IEEE Xplore were queried to identify randomized controlled trials that quantitatively investigated anatomy education via postintervention assessments of medical students or resident physicians who were exposed to 3DP versus traditional methods. Criteria for the meta-analysis required that studies additionally included a pre-intervention assessment. RESULTS: A total of 804 articles were reviewed, identifying 8 and 7 studies for systematic reviews of medical students and resident physicians, respectively, of which 4 and 7 were included in the meta-analyses. 3DP models were associated with higher anatomy examination scores for medical students (P < .0001), but for resident physicians were statistically not significant (P = .53). DISCUSSION: The 3DP models are shown to positively impact medical students especially given their limited fund of knowledge in anatomy. It is postulated that the lack of a statistically significant result for the resident physicians was multifactorial, in part because of the small test group sizes introducing noise and nonrepresentative samples, as well as relative simplicity of the 3DP models used with resident physicians, which were below their level of training. More trials are required to evaluate the usefulness of highly customized 3DP models.

Theranostics: Leveraging Molecular Imaging and Therapy to Impact Patient Management and Secure the Future of Nuclear Medicine.

Nuclear medicine is experiencing a renaissance, with U.S. Food and Drug Administration approval recently being obtained for theranostic agents and a wide variety of such agents soon to impact patient care significantly in the era of precision medicine. The NETTER-1 trial demonstrated the therapeutic effect of a theranostic agent in markedly improving progression-free survival in patients with metastatic gastroenteropancreatic neuroendocrine tumors. Predominantly retrospective studies have demonstrated a significant response to 177Lu-labeled agents targeting prostate-specific membrane antigen (PSMA) in patients with prostate cancer. At least 2 prospective clinical trials involving 177Lu-PSMA agents are under way that will likely pave the way for Food and Drug Administration approval in the United States. A significant upside to theranostics is that patients tend to tolerate these agents better than chemotherapy. Theranostic compounds are likely to impact many cancers in the near future, not only through improvements in quality of life but also in terms of survival. This article provides an overview of already approved agents as well as those on the horizon. It is important that as these agents are clinically onboarded, nuclear medicine physicians have the expertise to deploy theranostics safely and efficiently, ensuring that these agents attain and maintain their position as leading lines of therapy in managing patients with cancer as well as becoming an important aspect of nuclear medicine practice in the future.

APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume.

To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (ß = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (ß = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (ß= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (ß/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease.