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.

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.

Diagnostic Accuracy of SPECT for Mild Traumatic Brain Injury: A Systematic Review and Meta-analysis.

PURPOSE: This study examines the diagnostic accuracy of brain perfusion SPECT for mild traumatic brain injury (mTBI). PATIENTS AND METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO: CRD42023484636). Five databases were searched for studies evaluating brain perfusion SPECT in adult patients with mTBI (GCS 13-15). Study quality was assessed using a modified QUADAS-2 tool. A meta-analysis was performed to pool proportions of hypoperfusion abnormalities across brain lobes. RESULTS: Of 4735 records, 22 studies (5 longitudinal [40% high quality], 17 cross-sectional [24% high quality]) were included totaling 800 patients (mean age, 37.4 ± 12.6 years; 36.4% female). Meta-analysis of proportions indicated that the frontal lobe most frequently showed hypoperfusion on brain perfusion SPECT (pooled proportion 40.1% [95% confidence interval, 31.2% to 49.8%], 99/254, I2 = 54.5%), followed by the temporal lobe (26.1% [95% confidence interval, 19.9% to 33.6%], 68/254, I2 = 30.7%). Several studies found that hypoperfusion abnormalities were associated with neuropsychological findings. Also, brain perfusion SPECT could detect abnormalities not seen on MRI. Abnormalities in perfusion on brain perfusion SPECT may be more readily detected with a quantitative assessment compared with a visual assessment alone, although there appears to be no consensus on the optimal method for image interpretation. Evidence evaluating the sensitivity and specificity of brain perfusion SPECT for mTBI was limited. Using the GRADE framework, the evidence was rated as low. CONCLUSIONS: Although perfusion abnormalities can be seen in patients with mTBI, commonly in the frontal and temporal lobes, the findings are nonspecific and may derive from various factors. Ultimately, brain perfusion SPECT provides additional information for mTBI, but the final added value for the detection of mTBI is unknown.

Brain PET and Cerebrovascular Disease.

Cerebrovascular disease encompasses a broad spectrum of diseases such as stroke, hemorrhage, and cognitive decline associated with vascular narrowing, obstruction, rupture, and inflammation, among other issues. Recent advances in hardware and software have led to improvements in brain PET. Although still in its infancy, machine learning using convolutional neural networks is gaining traction in this area, often with a focus on providing high-quality images with reduced noise using a shorter acquisition time or less radiation exposure for the patient.

Pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy: an emerging problem and the role of radiologists in its management.

OBJECTIVE: The purpose of this article is to study the imaging features, management, and outcome of pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy. MATERIALS AND METHODS: In this retrospective study, 48 patients with cancer who developed pneumatosis or intestinal perforation were found by searching a radiology database. Of these patients, 24 patients (13 women and 11 men; mean age, 61 years; range, 39-83 years) receiving molecular targeted therapy without any confounding factors for pneumatosis or perforation were selected. Initial and follow-up CT scans were evaluated by two radiologists; medical records were reviewed to note clinical features, management, and outcome. RESULTS: Seventeen (70.8%) patients were asymptomatic. Colorectal cancer (n = 10) and renal cell carcinoma (n = 5) were the most common malignancies; bevacizumab (n = 14) and sunitinib (n = 6) were the most common associated drugs. Imaging findings included intestinal perforation (20 sites in 18 patients), pneumatosis (n = 10), ascites (n = 8), pneumoperitoneum (n = 7), fistula formation (n = 7), and fluid collections (six collections in five patients). Fifteen (62.5%) patients were treated conservatively, seven (29.2%) underwent surgery, and two (8.3%) underwent percutaneous drainage. Molecular targeted therapy was discontinued in 22 of 24 patients; findings resolved in 19 patients, remained stable in one, and worsened in one. One patient died after surgery. In both instances where the drug was continued, the abnormality worsened. Findings recurred in three of four patients in whom the drug was restarted after initial resolution. CONCLUSION: Radiologists should be aware of intestinal complications associated with molecular targeted therapy, including pneumatosis, bowel perforation, and fistula formation. Most patients can be treated conservatively after discontinuation of molecular targeted therapy. Continuing or restarting molecular targeted therapy can cause worsening or recurrent pneumatosis or perforation.

Evidence-Based Artificial Intelligence in Medical Imaging.

Artificial intelligence (AI) in medical imaging is in its infancy. However, ongoing advances in hardware and software as well as increasing access to ever-expanding datasets for training, validation, and testing purposes are likely to make AI an increasingly prevalent and powerful tool. Of course issues, such as the need to protect the privacy of sensitive health data, remain; nevertheless, it is likely the average imager will need to develop an evidence-based approach to assessing AI in medical imaging. We hope this article will provide insight into just how this can be conducted by applying 5 simple questions, specifically: (1) Who was in the training sample, (2) How was the model trained, (3) How reliable is the algorithm, (4) How was the model validated, and (5) How useable is the algorithm.

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.

Reduction in radiation dose in mercaptoacetyltriglycerine renography with enhanced planar processing.

PURPOSE: To determine the minimum dose of technetium 99m ((99m)Tc) mercaptoacetyltriglycerine (MAG3) needed to perform dynamic renal scintigraphy in the pediatric population without loss of diagnostic quality or accurate quantification of renal function and to investigate whether adaptive noise reduction could help further reduce the minimum dose required. MATERIALS AND METHODS: Approval for this retrospective study was obtained from the institutional review board, with waiver of informed consent. A retrospective review was conducted in 33 pediatric patients consecutively referred for a (99m)Tc-MAG3 study. In each patient, a 20-minute dynamic study was performed after administration of 7.4 MBq/kg. Binomial subsampling was used to simulate studies performed with 50%, 30%, 20%, and 10% of the administered dose. Four nuclear medicine physicians independently reviewed the original and subsampled images, with and without noise reduction, for image quality. Two observers independently performed a quantitative analysis of renal function. Subjective rater confidence was analyzed by using a logistic regression model, and the quantitative analysis was performed by using the paired Student t test. RESULTS: Reducing the administered dose to 30% did not substantially affect image quality, with or without noise reduction. When the dose was reduced to 20%, there was a slight but significant decrease (P = .0074) in image quality, which resolved with noise reduction. Reducing the dose to 10% caused a decrease in image quality (P = .0003) that was not corrected with noise reduction. However, the dose could be reduced to 10% without a substantial change in the quantitative evaluation of renal function independent of the application of noise reduction. CONCLUSION: Decreasing the dose of (99m)Tc-MAG3 from 7.4 to 2.2 MBq/kg did not compromise image quality. With noise reduction, the dose can be reduced to 1.5 MBq/kg without subjective loss in image quality. The quantitative evaluation of renal function was not substantially altered, even with a theoretical dose as low as 0.74 MBq/kg.

Brown adipose tissue 18F-FDG uptake in pediatric PET/CT imaging.

Positron emission tomography (PET) using [F-18]2-fluoro-2-deoxyglucose (FDG) fused with CT ((18)F-FDG PET/CT) has been widely adopted in oncological imaging. However, it is known that benign lesions and other metabolically active tissues, such as brown adipose tissue (BAT), can accumulate (18)F-FDG, potentially resulting in false-positive interpretation. Previous studies have reported that (18)F-FDG uptake in BAT is more common in children than in adults. We illustrate BAT FDG uptake in various anatomical locations in children and adolescents. We also review what is known about the effects of patient-related physical attributes and environmental temperatures on BAT FDG uptake, and discuss methods used to reduce BAT FDG uptake on (18)F-FDG PET.

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.

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.

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.

Seasonal variation in the effect of constant ambient temperature of 24 degrees C in reducing FDG uptake by brown adipose tissue in children.

PURPOSE: It has been shown that warming patients prior to and during (18)F-FDG uptake by controlling the room temperature can decrease uptake by brown adipose tissue (BAT). The aim of this study is to determine if this effect is subject to seasonal variation. METHODS: A retrospective review was conducted of all patients referred for whole-body (18)F-FDG PET between December 2006 and December 2008. After December 2007, all patients were kept in the PET injection room at a constant 24 degrees C for 30 min before and until 1 h following FDG administration. Patients over 22 years of age and those who received pre-medication known to reduce FDG uptake by BAT were excluded. One hundred and three patients were warmed to 24 degrees C prior to scanning. The number of patients showing uptake by BAT in this group was compared to a control group of 99 patients who underwent PET prior to December 2007 when the injection room temperature was 21 degrees C. RESULTS: Uptake by BAT occurred in 9% of studies performed after patient warming (24 degrees C), compared to 27% of studies performed on the control group (21 degrees C) (p < 0.00001). The effect of warming on decreasing FDG accumulation in BAT was statistically significant in the winter (p < 0.005) and summer (p < 0.001). However, in the spring and autumn, though the effect of warming on decreasing FDG accumulation in BAT was evident, it was not statistically significant (p > 0.05). CONCLUSION: Maintaining room temperature at a constant 24 degrees C for 30 min prior to and 1 h after IV tracer administration significantly decreases FDG uptake by BAT in children. This effect is greatest in the summer and winter.

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.