A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY).

PURPOSE: Prostate specific membrane antigen-targeted positron emission tomography/computerized tomography has the potential to improve the detection and localization of prostate cancer. OSPREY was a prospective trial designed to determine the diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography for detecting sites of metastatic prostate cancer. MATERIALS AND METHODS: Two patient populations underwent 18F-DCFPyL-positron emission tomography/computerized tomography. Cohort A enrolled men with high-risk prostate cancer undergoing radical prostatectomy with pelvic lymphadenectomy. Cohort B enrolled patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Three blinded central readers evaluated the 18F-DCFPyL-positron emission tomography/computerized tomography. Diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography was based on imaging results compared to histopathology. In cohort A, detection of pelvic nodal disease (with specificity and sensitivity as co-primary end points) and of extrapelvic metastases were evaluated. In cohort B, sensitivity and positive predictive value for prostate cancer within biopsied lesions were evaluated. RESULTS: A total of 385 patients were enrolled. In cohort A (252 evaluable patients), 18F-DCFPyL-positron emission tomography/computerized tomography had median specificity of 97.9% (95% CI: 94.5%-99.4%) and median sensitivity of 40.3% (28.1%-52.5%, not meeting prespecified end point) among 3 readers for pelvic nodal involvement; median positive predictive value and negative predictive value were 86.7% (69.7%-95.3%) and 83.2% (78.2%-88.1%), respectively. In cohort B (93 evaluable patients, median prostate specific antigen 11.3 ng/ml), median sensitivity and positive predictive value for extraprostatic lesions were 95.8% (87.8%-99.0%) and 81.9% (73.7%-90.2%), respectively. CONCLUSIONS: The primary end point for specificity was met while the primary end point for sensitivity was not. The high positive predictive value observed in both cohorts indicates that 18F-DCFPyL-positive lesions are likely to represent disease, supporting the potential utility of 18F-DCFPyL-positron emission tomography/computerized tomography to stage men with high-risk prostate cancer for nodal or distant metastases, and reliably detect sites of disease in men with suspected metastatic prostate cancer.

Voxel-based logistic analysis of PPMI control and Parkinson's disease DaTscans.

A comprehensive analysis of the Parkinson's Progression Markers Initiative (PPMI) Dopamine Transporter Single Photon Emission Computed Tomography (DaTscan) images is carried out using a voxel-based logistic lasso model. The model reveals that sub-regional voxels in the caudate, the putamen, as well as in the globus pallidus are informative for classifying images into control and PD classes. Further, a new technique called logistic component analysis is developed. This technique reveals that intra-population differences in dopamine transporter concentration and imperfect normalization are significant factors influencing logistic analysis. The interactions with handedness, sex, and age are also evaluated.

PET Image Denoising using a Deep-Learning Method for Extremely Obese Patients.

The image quality in clinical PET scan can be severely degraded due to high noise levels in extremely obese patients. Our work aimed to reduce the noise in clinical PET images of extremely obese subjects to the noise level of lean subject images, to ensure consistent imaging quality. The noise level was measured by normalized standard deviation (NSTD) derived from a liver region of interest. A deep learning-based noise reduction method with a fully 3D patch-based U-Net was used. Two U-Nets, U-Nets A and B, were trained on datasets with 40% and 10% count levels derived from 100 lean subjects, respectively. The clinical PET images of 10 extremely obese subjects were denoised using the two U-Nets. The results showed the noise levels of the images with 40% counts of lean subjects were consistent with those of the extremely obese subjects. U-Net A effectively reduced the noise in the images of the extremely obese patients while preserving the fine structures. The liver NSTD improved from 0.13±0.04 to 0.08±0.03 after noise reduction (p = 0.01). After denoising, the image noise level of extremely obese subjects was similar to that of lean subjects, in terms of liver NSTD (0.08±0.03 vs. 0.08±0.02, p = 0.74). In contrast, U-Net B over-smoothed the images of extremely obese patients, resulting in blurred fine structures. In a pilot reader study comparing extremely obese patients without and with U-Net A, the difference was not significant. In conclusion, the U-Net trained by datasets from lean subjects with matched count level can provide promising denoising performance for extremely obese subjects while maintaining image resolution, though further clinical evaluation is needed.

Clinical PET/CT utilization during the COVID-19 pandemic: initial experience at Yale University.

OBJECTIVE: To determine temporal changes in PET/CT utilization during the COVID-19 pandemic and examine the impact of epidemiologic, demographic and oncologic factors on PET/CT utilization. METHODS: Clinical PET-CT utilization between 1 January 2020 and 15 June 2020 at a tertiary academic center was assessed using change-point-detection (CPD) analysis. COVID-19 epidemiologic trend was obtained from Connecticut Department of Public Health records. Demographic and oncologic data were gathered from electronic medical records and PET-CT scans by four reviewers in consensus. RESULTS: A total of 1685 cases were reviewed. CPD analysis identified five distinct phases of PET-CT utilization during COVID-19, with a sharp decline and a gradual recovery. There was a 62.5% decline in case volumes at the nadir. These changes correlated with COVID-19 epidemiologic changes in the state of Connecticut, with a negative correlation between COVID-19 cases and PET-CT utilization (τ = -0.54; P value < 0.001). Statistically significant differences in age, race, cancer type and current and prior scan positivity were observed in these five phases. A greater percentage of young patients and minorities were scanned during the pandemic relative to baseline. PET/CT scanning was less impacted for hematologic malignancies than for solid cancers, with less profound decline and better recovery. DISCUSSION: PET-CT cancer imaging was vulnerable to the COVID-19 pandemic at our institution. Epidemiologic, demographic and oncologic factors affected PET-CT utilization.

Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study.

PURPOSE: Current FDA-approved imaging modalities are inadequate for localizing prostate cancer biochemical recurrence (BCR). 18F-DCFPyL is a highly selective, small-molecule prostate-specific membrane antigen-targeted PET radiotracer. CONDOR was a prospective study designed to determine the performance of 18F-DCFPyL-PET/CT in patients with BCR and uninformative standard imaging. EXPERIMENTAL DESIGN: Men with rising PSA ≥0.2 ng/mL after prostatectomy or ≥2 ng/mL above nadir after radiotherapy were eligible. The primary endpoint was correct localization rate (CLR), defined as positive predictive value with an additional requirement of anatomic lesion colocalization between 18F-DCFPyL-PET/CT and a composite standard of truth (SOT). The SOT consisted of, in descending priority (i) histopathology, (ii) subsequent correlative imaging findings, or (iii) post-radiation PSA response. The trial was considered a success if the lower bound of the 95% confidence interval (CI) for CLR exceeded 20% for two of three 18F-DCFPyL-PET/CT readers. Secondary endpoints included change in intended management and safety. RESULTS: A total of 208 men with a median baseline PSA of 0.8 ng/mL (range: 0.2-98.4 ng/mL) underwent 18F-DCFPyL-PET/CT. The CLR was 84.8%-87.0% (lower bound of 95% CI: 77.8-80.4). A total of 63.9% of evaluable patients had a change in intended management after 18F-DCFPyL-PET/CT. The disease detection rate was 59% to 66% (at least one lesion detected per patient by 18F-DCFPyL-PET/CT by central readers). CONCLUSIONS: Performance of 18F-DCFPyL-PET/CT achieved the study's primary endpoint, demonstrating disease localization in the setting of negative standard imaging and providing clinically meaningful and actionable information. These data further support the utility of 18F-DCFPyL-PET/CT to localize disease in men with recurrent prostate cancer.See related commentary by True and Chen, p. 3512.

Fluorodeoxyglucose PET for Monitoring Response to Embolotherapy (Transarterial Chemoembolization) in Primary and Metastatic Liver Tumors.

Response to transarterial chemoembolization (TACE) in patients with liver cancer is commonly assessed on MRI or CT to quantify tumor necrosis and morphologic changes that occur gradually. However, the efficacy of embolotherapies remains limited because of local recurrence, as treated tumors demonstrate individual molecular characteristics that alter susceptibility and response to embolotherapies. Upregulation of cancer cell glycolysis can be detected by fluorine-18-fluorodeoxyglucose PET. Therefore, the combination of functional (PET) with commonly used cross-sectional imaging techniques (MRI, CT) can help characterize and monitor liver tumors with the potential to improve TACE toward becoming a more personalized and tumor microenvironment-directed therapy.

Single-photon Emission Computed Tomography-Computed Tomography Using 99mTc-labeled Leukocytes for Evaluating Infection Associated with a Cranial Implant in a Rhesus Macaque (Macaca mulatta).

An adult male rhesus macaque (Macaca mulatta) that was enrolled in a study evaluating cognition and memory presented with suppurative exudate along the margins of a long-standing cranial implant that included a stainless-steel head post, plastic left-sided recording cylinder, and acrylic over a previously placed right-sided recording cylinder. Both cylinders were located at the level of the prefrontal cortex. After treatment comprising systemic antibiotics and daily cleaning with povidone-iodine for several months, the macaque underwent single-photon emission computed tomography-computed tomography (SPECT-CT) in which his neutrophils were labeled with 99mTc-hexamethylpropylene amine oxime ( 99m Tc-HMPAO) to evalu- ate for active infection below the implant. Soft tissue inflammation and osteomyelitis were found at the site of the previous right-sided recording cylinder. Cephalosporin and tetracycline antibiotics were administered for 12 wk. Follow-up SPECT-CT imaging was then performed to evaluate response to medical treatment. Results indicated no change in the degrees of soft tissue inflammation and osteomyelitis associated with the right-sided recording cylinder site. SPECT-CT imaging was used to guide the surgical removal of the implant and debridement of the infected tissue. On removal of the entire cranial implant, the osteomyelitis and soft tissue inflammation observed on the pre- and posttreatment SPECT-CT scans were confirmed. In addition, a large cavitary defect through the calvarium with suppurative exudate was discovered below the base of the head post. Infection in this defect was not apparent on SPECT; however, the bony defect was confirmed on reevaluation of the CT images. We concluded that the infection in this defect was silent on SPECT due to the limited vascularization of the sur-rounding bone and the chronicity of the infection. This case study is the first to describe the use of SPECT-CT for evaluating soft tissue inflammation and osteomyelitis beneath a cranial implant in a NHP.

Quantitative Imaging Biomarkers for 90Y Distribution on Bremsstrahlung SPECT After Resin-Based Radioembolization.

Our purpose was to identify baseline imaging features in patients with liver cancer that correlate with 90Y distribution on postprocedural SPECT and predict tumor response to transarterial radioembolization (TARE). Methods: This retrospective study was approved by the institutional review board and included 38 patients with hepatocellular carcinoma (HCC) (n = 23; 18/23 men; mean age, 62.39 ± 8.62 y; 34 dominant tumors) and non-HCC hepatic malignancies (n = 15; 9/15 men; mean age, 61.13 ± 11.51 y; 24 dominant tumors) who underwent 40 resin-based TARE treatments (August 2012 to January 2018). Multiphasic contrast-enhanced MRI or CT was obtained before and Bremsstrahlung SPECT within 2 h after TARE. Total tumor volume (cm3) and enhancing tumor volume (ETV [cm3] and % of total tumor volume), and total and enhancing tumor burden (%), were volumetrically assessed on baseline imaging. Up to 2 dominant tumors per treated lobe were analyzed. After multimodal image registration of baseline imaging and SPECT/CT, 90Y distribution was quantified on SPECT as tumor-to-normal-liver ratio (TNR). Response was assessed according to RECIST1.1 and quantitative European Association for the Study of the Liver criteria. Clinical parameters were also assessed. Statistical tests included Mann-Whitney U, Pearson correlation, and linear regression. Results: In HCC patients, high baseline ETV% significantly correlated with high TNR on SPECT, demonstrating greater 90Y uptake in the tumor relative to the liver parenchyma (P < 0.001). In non-HCC patients, a correlation between ETV% and TNR was observed as well (P = 0.039). Follow-up imaging for response assessments within 1-4 mo after TARE was available for 23 patients with 25 treatments. The change of ETV% significantly correlated with TNR in HCC (P = 0.039) but not in non-HCC patients (P = 0.886). Additionally, Child-Pugh class B patients demonstrated significantly more 90Y deposition in nontumorous liver than Child-Pugh A patients (P = 0.021). Conclusion: This study identified ETV% as a quantifiable imaging biomarker on preprocedural MRI and CT to predict 90Y distribution on postprocedural SPECT in HCC and non-HCC. However, the relationship between the preferential uptake of 90Y to the tumor and tumor response after radioembolization could be validated only for HCC.

Isolated Multinodular Soft-Tissue Rosai-Dorfman Disease on FDG PET/CT.

Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) is a rare systemic histiocytic disorder of unknown etiology characterized by the accumulation of enlarged non-Langerhans histiocytes within lymph nodes and extranodal sites. The histiocytes display characteristic emperipolesis (nondestructive engulfment of inflammatory cells) and are CD68 and S100 positive and CD1a negative. Although extranodal disease frequently occurs with nodal involvement, isolated extranodal disease is uncommon. We report a case of isolated localized subcutaneous multinodular disease on FDG PET/CT. We also include a companion classic Rosai-Dorfman case with extensive nodal involvement and a characteristic benign clinical course with spontaneous improvement.

Molecular imaging of prostate cancer.

Prostate cancer is a common malignancy with various treatments from surveillance, surgery, radiation and chemotherapy. The institution of appropriate, effective treatment relies in part on accurate imaging. Molecular imaging techniques offer an opportunity for increased timely detection of prostate cancer, its recurrence, as well as metastatic disease. Advancements within the field of molecular imaging have been complex with some agents targeting receptors and others acting as metabolic intermediaries. In this article, we provide an overview of the most clinically relevant radiotracers to date based on a combination of the five states model and the National Comprehensive Cancer Network Guidelines.

Superior Pituitary Border Analysis in Immunotherapy-Induced Hypophysitis.

Immunotherapy-induced hypophysitis presents with headache, fatigue, and visual disturbances. The diagnosis is supported by imaging findings of pituitary swelling, enhancement, and hypermetabolism and established by low levels of pituitary hormones. A 64-year-old man with metastatic melanoma on nivolumab presented with a severe headache, initially attributed to sinus disease. Contrast CT was interpreted as minor sinus disease and no pituitary abnormality. Hypophysitis was eventually diagnosed and successfully treated based on PET and laboratory findings. Our retrospective analysis demonstrated abnormal convex superior pituitary border visible on contrast and noncontrast CT and PET. This feature may aid diagnosis in the challenging cases.

Intraoperative Injection of Technetium-99m Sulfur Colloid for Sentinel Lymph Node Biopsy in Breast Cancer Patients: A Single Institution Experience.

Background. Most institutions require a patient undergoing sentinel lymph node biopsy to go through nuclear medicine prior to surgery to be injected with radioisotope. This study describes the long-term results using intraoperative injection of radioisotope. Methods. Since late 2002, all patients undergoing a sentinel lymph node biopsy at the Yale-New Haven Breast Center underwent intraoperative injection of technetium-99m sulfur colloid. Endpoints included number of sentinel and nonsentinel lymph nodes obtained and number of positive sentinel and nonsentinel lymph nodes. Results. At least one sentinel lymph node was obtained in 2,333 out of 2,338 cases of sentinel node biopsy for an identification rate of 99.8%. The median number of sentinel nodes found was 2 and the mean was 2.33 (range: 1-15). There were 512 cases (21.9%) in which a sentinel node was positive for metastatic carcinoma. Of the patients with a positive sentinel lymph node who underwent axillary dissection, there were 242 cases (54.2%) with no additional positive nonsentinel lymph nodes. Advantages of intraoperative injection included increased comfort for the patient and simplification of scheduling. There were no radiation related complications. Conclusion. Intraoperative injection of technetium-99m sulfur colloid is convenient, effective, safe, and comfortable for the patient.