Image acquisition and interpretation of 18F-DCFPyL (piflufolastat F 18) PET/CT: How we do it.

Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is rapidly becoming widely accepted as the standard-of-care for imaging of men with prostate cancer. Labeled indications for regulatoryapproved agents include primary staging and recurrent disease in men at risk of metastases. The first commercial PSMA PET agent to become available was 18F-DCFPyL (piflufolastat F 18), a radiofluorinated small molecule with high-affinity for PSMA. The regulatory approval of 18F-DCFPyL hinged upon two key, multi-center, registration trials, OSPREY (patient population: highrisk primary staging) and CONDOR (patient population: biochemical recurrence). In this manuscript, we will (1) review key findings from the OSPREY and CONDOR trials, (2) discuss the clinical acquisition protocol we use for 18F-DCFPyL PET scanning, (3) present information on important pearls and pitfalls, (4) provide an overview of the PSMA reporting and data system (PSMA-RADS) interpretive framework, and (5) posit important future directions for research in PSMA PET. Our overall goal is to provide a brief introduction for practices and academic groups that are adopting 18F-DCFPyL PET scans for use in their patients with prostate cancer.

Clinical Applications of Artificial Intelligence in Positron Emission Tomography of Lung Cancer.

The ability of a computer to perform tasks normally requiring human intelligence or artificial intelligence (AI) is not new. However, until recently, practical applications in medical imaging were limited, especially in the clinic. With advances in theory, microelectronic circuits, and computer architecture as well as our ability to acquire and access large amounts of data, AI is becoming increasingly ubiquitous in medical imaging. Of particular interest to our community, radiomics tries to identify imaging features of specific pathology that can represent, for example, the texture or shape of a region in the image. This is conducted based on a review of mathematical patterns and pattern combinations. The difficulty is often finding sufficient data to span the spectrum of disease heterogeneity because many features change with pathology as well as over time and, among other issues, data acquisition is expensive. Although we are currently in the early days of the practical application of AI to medical imaging, research is ongoing to integrate imaging, molecular pathobiology, genetic make-up, and clinical manifestations to classify patients into subgroups for the purpose of precision medicine, or in other words, predicting a priori treatment response and outcome. Lung cancer is a functionally and morphologically heterogeneous disease. Positron emission tomography (PET) is an imaging technique with an important role in the precision medicine of patients with lung cancer that helps predict early response to therapy and guides the selection of appropriate treatment. Although still in its infancy, early results suggest that the use of AI in PET of lung cancer has promise for the detection, segmentation, and characterization of disease as well as for outcome prediction.

Update on Molecular Imaging and Precision Medicine in Lung Cancer.

Precision medicine integrates molecular pathobiology, genetic make-up, and clinical manifestations of disease in order to classify patients into subgroups for the purposes of predicting treatment response and suggesting outcome. By identifying those patients who are most likely to benefit from a given therapy, interventions can be tailored to avoid the expense and toxicity of futile treatment. Ultimately, the goal is to offer the right treatment, to the right patient, at the right time. Lung cancer is a heterogeneous disease both functionally and morphologically. Further, over time, clonal proliferations of cells may evolve, becoming resistant to specific therapies. PET is a sensitive imaging technique with an important role in the precision medicine algorithm of lung cancer patients. It provides anatomo-functional insight during diagnosis, staging, and restaging of the disease. It is a prognostic biomarker in lung cancer patients that characterizes tumoral heterogeneity, helps predict early response to therapy, and may direct the selection of appropriate treatment.

Artificial intelligence for molecular neuroimaging.

In recent years, artificial intelligence (AI) or the study of how computers and machines can gain intelligence, has been increasingly applied to problems in medical imaging, and in particular to molecular imaging of the central nervous system. Many AI innovations in medical imaging include improving image quality, segmentation, and automating classification of disease. These advances have led to an increased availability of supportive AI tools to assist physicians in interpreting images and making decisions affecting patient care. This review focuses on the role of AI in molecular neuroimaging, primarily applied to positron emission tomography (PET) and single photon emission computed tomography (SPECT). We emphasize technical innovations such as AI in computed tomography (CT) generation for the purposes of attenuation correction and disease localization, as well as applications in neuro-oncology and neurodegenerative diseases. Limitations and future prospects for AI in molecular brain imaging are also discussed. Just as new equipment such as SPECT and PET revolutionized the field of medical imaging a few decades ago, AI and its related technologies are now poised to bring on further disruptive changes. An understanding of these new technologies and how they work will help physicians adapt their practices and succeed with these new tools.

Prospective, Single-Arm Trial Evaluating Changes in Uptake Patterns on Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT in Patients with Castration-Resistant Prostate Cancer Starting Abiraterone or Enzalutamide.

PET with small molecules targeting prostate-specific membrane antigen (PSMA) is being adopted as a clinical standard for prostate cancer imaging. In this study, we evaluated changes in uptake on PSMA-targeted PET in men starting abiraterone or enzalutamide. Methods: This prospective, single-arm, 2-center, exploratory clinical trial enrolled men with metastatic castration-resistant prostate cancer initiating abiraterone or enzalutamide. Each patient was imaged with 18F-DCFPyL at baseline and within 2-4 mo after starting therapy. Patients were followed for up to 48 mo from enrollment. A central review evaluated baseline and follow-up PET scans, recording change in SUVmax at all disease sites and classifying the pattern of change. Two parameters were derived: the δ-percent SUVmax (DPSM) of all lesions and the δ-absolute SUVmax (DASM) of all lesions. Kaplan-Meier curves were used to estimate time to therapy change (TTTC) and overall survival (OS). Results: Sixteen evaluable patients were accrued to the study. Median TTTC was 9.6 mo (95% CI, 6.9-14.2), and median OS was 28.6 mo (95% CI, 18.3-not available [NA]). Patients with a mixed-but-predominantly-increased pattern of radiotracer uptake had a shorter TTTC and OS. Men with a low DPSM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of 37.2 mo (95% CI, 28.9-NA), whereas those with a high DPSM had a median TTTC of 6.5 mo (95% CI, 4.6-NA, P = 0.0001) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.02). Men with a low DASM had a median TTTC of 12.2 mo (95% CI, 11.3-NA) and a median OS of NA (95% CI, 37.2 mo-NA), whereas those with a high DASM had a median TTTC of 6.9 mo (95% CI, 6.1-NA, P = 0.003) and a median OS of 17.8 mo (95% CI, 13.9-NA, P = 0.002). Conclusion: Findings on PSMA-targeted PET 2-4 mo after initiation of abiraterone or enzalutamide are associated with TTTC and OS. Development of new lesions or increasing intensity of radiotracer uptake at sites of baseline disease are poor prognostic findings suggesting shorter TTTC and OS.

Internal Jugular Vein and Cerebral Venous Sinus Infective Thrombophlebitis Detected With 99mTc-HMPAO White Blood Cell Scintigraphy.

ABSTRACT: A 35-year-old man with a history of renal transplant, congenital cystinosis, and diabetes was admitted to the hospital with fever, bilateral parotid gland swelling, and acute renal failure. He had 99mTc-HMPAO-WBC (99mTc-hexamethylpropyleneamineoxime white blood cell) imaging for the evaluation of possible parotitis. There was intense radiopharmaceutical uptake along the right internal jugular vein extending to the right sigmoid and transverse and superior sagittal sinuses, suggestive of infective thrombophlebitis or Lemierre syndrome. This study illustrates the value of 99mTc-HMPAO-WBC imaging as a tool for evaluating thrombophlebitis, particularly in patients with renal failure in whom contrast-enhanced CT may not be possible.

Prostate Cancer Lymphangitic Pulmonary Carcinomatosis: Appearance on 18F-FDG PET/CT and 18F-DCFPyL PET/CT.

A 51-year-old man diagnosed with high-grade, high-volume metastatic castration-sensitive prostate adenocarcinoma received pelvic radiation, androgen deprivation therapy, and intravenous docetaxel. Serum prostate-specific antigen became undetectable following treatment. Within a year, his cancer progressed to castration-resistant disease, and he was treated with oral abiraterone acetate 1000 mg and prednisone 10 mg daily. Despite this, the serum prostate-specific antigen rose from 0.03 to 1.39 µg/L, and F-DCFPyL and F-FDG PET/CT showed progression. While F-DCFPyL uptake may be seen in aggressive disease, F-FDG portends poor prognosis. Despite intravenous platinum-based chemotherapy, the patient died of respiratory failure 20 months after his initial diagnosis.

18F-DCFPyL PET/CT in Oncocytoma.

A 76-year-old man with biochemical failure after primary radiotherapy for prostate cancer had no malignant disease detected on Tc-MDP bone scan and diagnostic CT. Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein, is overexpressed in prostate cancer cells. The PSMA-targeted F-DCFPyL PET/CT demonstrated lymph node disease and photopenic defects in the left kidney associated with a cyst and biopsy-proven oncocytoma. Prostate-specific membrane antigen is expressed in the neovasculature of several solid tumors. It has been reported that PSMA expression is seen in approximately 50% of oncocytoma versus 76% of clear cell renal carcinomas. Biopsy confirmation is needed regardless of F-DCFPyL avidity.

A dose finding clinical trial of cabozantinib (XL184) administered in combination with abiraterone acetate in metastatic castration-resistant prostate cancer.

BACKGROUND: Cabozantinib can enhance the effect of abiraterone in preclinical prostate cancer models. This study aimed to define the recommended phase 2 dose (RP2D) and preliminary efficacy of abiraterone + cabozantinib in mCRPC. METHODS: Patients with progressive mCRPC with 0-2 prior chemotherapy regimens but no prior CYP17A1 or MET inhibitor received abiraterone acetate at 1000 mg daily with prednisone 5 mg BID in combination with cabozantinib at 20, 40, or 60 mg daily in a dose-escalation 3 + 3 open-label phase 1 design (Part A). After tolerable doses were defined, cohorts were expanded to better define toxicity and efficacy (Part B). RESULTS: There were no dose-limiting toxicities (DLTs) in the first 4 weeks at any of the three dose levels in Part A. Two of the three patients at the 60 mg dose level required dose reductions beyond cycle 2 due to fatigue. In Part B, nine more patients were accrued to each of the 20 and 40 mg doses. Of the 12 patients treated at the 40 mg dose, only one DLT (grade 3 Lipase elevation) was observed in cycle 1. The median time to radiographic progression was 12.88 months (95% CI:5.42- not estimated [NE]) in the 20 mg cohort and 22.01 months (95% CI:15.44-NE) in the 40 mg cohort. Median overall survival was 23.29 months (95% CI:19.06-NE) in the 20 mg cohort and 39.08 months (95% CI:17.38-NE) in the 40 mg cohort. CONCLUSIONS: Based on tolerability and preliminary efficacy, 40 mg cabozantinib plus 1000 mg abiraterone daily is the RP2D.

Flare on Serial Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT Examinations in Castration-Resistant Prostate Cancer: First Observations.

A 71-year-old man with castration-resistant prostate cancer demonstrated a flare phenomenon on Tc-MDP and CT after 10 weeks of enzalutamide. Prostate-specific membrane antigen-targeted F-DCFPyL PET/CT demonstrated minimal uptake at sites of baseline bone and lymph node disease with increasing uptake at sites of osseous disease following therapy. Although this is likely related in part to decreased androgen receptor activity and a consequent increase in prostate-specific membrane antigen expression, other mechanisms (neovascularization, cell infiltration from the bone repair process, osteoblastic turnover, or minimal radiotracer impurity) may also be involved in causing the increased F-DCFPyL uptake at sites of osseous flare.

Molecular Imaging and Precision Medicine in Uterine and Ovarian Cancers.

Gynecologic cancer is a heterogeneous group of diseases both functionally and morphologically. Today, PET coupled with computed tomography (PET/CT) or PET/MR imaging play a central role in the precision medicine algorithm of patients with gynecologic malignancy. In particular, PET/CT and PET/MR imaging are molecular imaging techniques that not only are useful tools for initial staging and restaging but provide anatomofunctional insight and can serve as predictive and prognostic biomarkers of response in patients with gynecologic malignancy.

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

The purpose of this study was to describe baseline 18F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher values of ADC-PET correlation had more favorable PFS (hazard ratio, 0.17; 95% CI, 0.03-0.89 [P = 0.036]), suggesting that a higher level of negative ADC-PET correlation leads to less favorable PFS. A more significant negative correlation may indicate higher-grade elements within the tumor leading to poorer outcomes. Conclusion:18F-FDG PET and MR ADC histogram metrics in pediatric DIPG demonstrate different characteristics with often a negative correlation between PET and MR ADC pixel values. A higher negative correlation is associated with a worse PFS, which may indicate higher-grade elements within the tumor.

Desirable Properties of Radiopharmaceuticals for Sentinel Node Mapping in Patients With Breast Cancer Given the Paradigm Shift in Patient Management.

Over the past 2 decades, lymphoscintigraphy and sentinel node biopsy have become widely accepted and are used by surgeons to stage many solid cancers, especially breast cancer. However, despite growing experience, there are a number of unresolved issues. In addition, the impact of a new radiopharmaceutical remains to be determined. The present article addresses some of these issues (either unresolved, recurrent, or newly emerged), with a focus on the properties of radiopharmaceuticals used for sentinel node mapping in breast cancer.

A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer.

Purpose: Despite the efficacy of abiraterone, a CYP17A1 inhibitor, in metastatic castration-resistant prostate cancer (CRPC), nearly all patients develop resistance. The purpose of this phase II study was to evaluate mechanisms of resistance to more complete androgen synthesis inhibition with abiraterone and dutasteride.Experimental Design: Eligible patients with metastatic CRPC underwent a baseline metastasis biopsy. Patients received abiraterone and prednisone for two 4-week cycles. After this time, high-dose dutasteride (3.5 mg daily) was added. Patients continued therapy until study withdrawal or radiographic progression. Repeat metastasis biopsy was obtained at progression. The primary endpoint was to assess mechanisms of resistance. Serum hormone and abiraterone levels were assessed. Tissue was assessed for androgen receptor (AR) and AR splice variant-7 (ARV7) expression.Results: Forty patients were enrolled. Sixty percent (n = 24) achieved a ≥50% reduction in prostate-specific antigen (PSA). The median time to radiographic progression was 11 months. Nearly all baseline (n = 29 of 31) and posttreatment (n = 16 of 16) tumors tested for AR nuclear expression were positive. Of those tested, ARV7 expression was present in 48% (n = 10 of 21) of baseline and 42% (n = 5 of 12) of treatment discontinuation specimens. Compared with patients with higher serum abiraterone levels at treatment discontinuation, patients with lower levels had higher circulating androgens.Conclusions: Despite increased androgen synthesis inhibition, we demonstrate that tumor AR axis remains important in disease progression. We highlight that abiraterone metabolism and pharmacokinetics may play a role in resistance. The noncomparative design limits conclusions on the efficacy of dual therapy with abiraterone and dutasteride, but the results support development of further multifaceted approaches toward AR inhibition. Clin Cancer Res; 23(4); 935-45. ©2016 AACR.

Molecular Imaging and Precision Medicine in Lung Cancer.

Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer.

Gender Differences in Radiation Dose From Nuclear Cardiology Studies Across the World: Findings From the INCAPS Registry.

OBJECTIVES: The aim of this study was to investigate gender-based differences in nuclear cardiology practice globally, with a particular focus on laboratory volume, radiation dose, protocols, and best practices. BACKGROUND: It is unclear whether gender-based differences exist in radiation exposure for nuclear cardiology procedures. METHODS: In a large, multicenter, observational, cross-sectional study encompassing 7,911 patients in 65 countries, radiation effective dose was estimated for each examination. Patient-level best practices relating to radiation exposure were compared between genders. Analysis of covariance was used to determine any difference in radiation exposure according to gender, region, and the interaction between gender and region. Linear, logistic, and hierarchical regression models were developed to evaluate gender-based differences in radiation exposure and laboratory adherence to best practices. The study also included the United Nations Gender Inequality Index and Human Development Index as covariates in multivariable models. RESULTS: The proportion of myocardial perfusion imaging studies performed in women varied among countries; however, there was no significant correlation with the Gender Inequality Index. Globally, mean effective dose for nuclear cardiology procedures was only slightly lower in women (9.6 ± 4.5 mSv) than in men (10.3 ± 4.5 mSv; p < 0.001), with a difference of only 0.3 mSv in a multivariable model adjusting for patients' age and weight. Stress-only imaging was performed more frequently in women (12.5% vs. 8.4%; p < 0.001); however, camera-based dose reduction strategies were used less frequently in women (58.6% vs. 65.5%; p < 0.001). CONCLUSIONS: Despite significant worldwide variation in best practice use and radiation doses from nuclear cardiology procedures, only small differences were observed between genders worldwide. Regional variations noted in myocardial perfusion imaging use and radiation dose offer potential opportunities to address gender-related differences in delivery of nuclear cardiology care.