Scintigraphy of Gastrointestinal Motility: Best Practices in Assessment of Gastric and Bowel Transit in Adults.

Various radiologic examinations and other diagnostic tools exist for evaluating gastrointestinal diseases. When symptoms of gastrointestinal disease persist and no underlying anatomic or structural abnormality is identified, the diagnosis of functional gastrointestinal disorder is frequently applied. Given its physiologic and quantitative nature, scintigraphy often plays a central role in the diagnosis and treatment of patients with suspected functional gastrointestinal disorder. Most frequently, after functional gallbladder disease is excluded, gastric emptying scintigraphy (GES) is considered the next step in evaluating patients with suspected gastric motility disorder who present with upper gastrointestinal symptoms such as dyspepsia or bloating. GES is the standard modality for detecting delayed gastric emptying (gastroparesis) and the less commonly encountered clinical entity, gastric dumping syndrome. Additionally, GES can be used to assess abnormalities of intragastric distribution, suggesting specific disorders such as impaired fundal accommodation or antral dysfunction, as well as to evaluate gastric emptying of liquid. More recently, scintigraphic examinations for evaluating small bowel and large bowel transit have been developed and validated for routine diagnostic use. These can be performed individually or as part of a comprehensive whole-gut transit evaluation. Such scintigraphic examinations are of particular importance because clinical assessment of suspected functional gastrointestinal disorder frequently fails to accurately localize the site of disease, and those patients may have motility disorders involving multiple portions of the gastrointestinal tract. The authors comprehensively review the current practice of gastrointestinal transit scintigraphy, with diseases and best imaging practices illustrated by means of case review. ©RSNA, 2024 See the invited commentary by Maurer and Parkman in this issue.

Molecular Imaging of Infections: Emerging Techniques for Pathogen-Specific Diagnosis and Guided Therapy.

Evaluation of patients that may be infected is challenging. Imaging to identify or localize a site of infection is often limited because of the nonspecific nature of the findings on conventional imaging modalities. Available imaging methods lack the ability to determine if antibiotics are reaching the site of infection and are not optimized to follow response to therapy. Positron emission tomography (PET) is a method by which radiolabeled molecules can be used to detect metabolic perturbations or levels of expression of specific targets. The most common PET agent is the glucose analog 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG). 18F-FDG has some applicability to localizing a site of infection, but its lack of specificity limits its usefulness. There is a need for the development of pathogen-specific PET radiotracers to address the imaging shortcomings noted above. Preclinical and clinical progress has been made, but significant challenges remain.

[18F]FNDP PET neuroimaging test-retest repeatability and whole-body dosimetry in humans.

PURPOSE: Soluble epoxide hydrolase (sEH) is an enzyme that shapes immune signaling through its role in maintaining the homeostasis of polyunsaturated fatty acids and their related byproducts. [18F]FNDP is a radiotracer developed for use with positron emission tomography (PET) to image sEH, which has been applied to imaging sEH in the brains of healthy individuals. Here, we report the test-retest repeatability of [18F]FNDP brain PET binding and [18F]FNDP whole-body dosimetry in healthy individuals. METHODS: Seven healthy adults (4 men, 3 women, ages 40.1 ± 4.6 years) completed [18F]FNDP brain PET on two occasions within a period of 14 days in a test-retest study design. [18F]FNDP regional total distribution volume (VT) values were derived from modeling time-activity data with a metabolite-corrected arterial input function. Test-retest variability, mean absolute deviation, and intraclass correlation coefficient (ICC) were investigated. Six other healthy adults (3 men, 3 women, ages 46.0 ± 7.0 years) underwent [18F]FNDP PET/CT for whole-body dosimetry, which was acquired over 4.5 h, starting immediately after radiotracer administration. Organ-absorbed doses and the effective dose were then estimated. RESULTS: The mean test-retest difference in regional VT (ΔVT) was 0.82 ± 5.17%. The mean absolute difference in regional VT was 4.01 ± 3.33%. The ICC across different brain regions ranged from 0.92 to 0.99. The organs with the greatest radiation-absorbed doses included the gallbladder (0.081 ± 0.024 mSv/MBq), followed by liver (0.077 ± 0.018 mSv/MBq) and kidneys (0.063 ± 0.006 mSv/MBq). The effective dose was 0.020 ± 0.003 mSv/MBq. CONCLUSION: These data support a favorable test-retest repeatability of [18F]FNDP brain PET regional VT. The radiation dose to humans from each [18F]FNDP PET scan is similar to that of other 18F-based PET radiotracers.

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.

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.

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.

Diagnostic performance of IQ·SPECT with high-speed scanning: A preliminary quality control study in obese patients.

BACKGROUND: IQ·SPECT is a recently introduced collimator design for myocardial perfusion imaging (MPI). Little data exist on use of this collimator type in obese patients, particularly Class 2 or 3 [body mass index (BMI) > 35 kg/m2]. METHODS: Two consecutive rest-stress MPI scans were prospectively acquired using a conventional collimator and IQ·SPECT (acquisition times of 20 and 7 minutes, respectively) in 20 patients with a BMI of >30 kg/m2. Assigned by two blinded, independent readers, image quality (on a 5-point scale) and metrics of myocardial perfusion [summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS)] were compared. Software-based left ventricular ejection fraction (EF) was also correlated. RESULTS: Mean BMI was 39.6 ± 7.6 kg/m2. Class 2 or 3 obesity was present in 12 patients (BMI, 44.1 ± 6.8 kg/m2). Gated/non-gated images from IQ·SPECT revealed fair to good quality scores (median ≥ 3.25), which were inferior to the conventional collimator (median ≥ 4.0; P ≤ 0.01). Significant correlative indices were achieved when comparing IQ·SPECT and conventional collimators for EF values (r = 0.86, P < 0.01), SSS (r = 0.75, P < 0.0001) and SRS (r = 0.60, P < 0.005), but not for SDS (r = 0.15). CONCLUSION: IQ·SPECT was comparable to conventional SPECT in obese patients. The reduced acquisition time of IQ·SPECT may allow for improved throughput with no loss in diagnostic accuracy.

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.

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.

Imager-4D: New Software for Viewing Dynamic PET Scans and Extracting Radiomic Parameters from PET Data.

Extensive research is currently being conducted into dynamic positron emission tomography (PET) acquisitions (including dynamic whole-body imaging) as well as extraction of radiomic features from imaging modalities. We describe a new PET viewing software known as Imager-4D that provides a facile means of viewing and analyzing dynamic PET data and obtaining associated quantitative metrics including radiomic parameters. The Imager-4D was programmed in the Java language utilizing the FX extensions. It is executable on any system for which a Java w/FX compliant virtual machine is available. The software incorporates the ability to view and analyze dynamic data acquired with different types of dynamic protocols. For image display, the program maintains a built-in library of 62 different lookup tables with monochromatic and full-color distributions. The Imager-4D provides multiple display layouts and can display fused images. Multiple methods of volume-of-interest (VOI) selection are available. Dynamic analysis features, such as image summation and full Patlak analysis, are also available. The user interface includes window width and level, blending, and zoom functionality. VOI sizes are adjustable and data from VOIs can either be displayed numerically or graphically within the software or exported. An example case of a 50-year-old woman with metastatic colorectal cancer and thyroiditis is included and demonstrates the steps for a user to obtain standard PET parameters, dynamic data, and radiomic features using selected VOIs. The Imager-4D represents a novel PET viewer that allows the user to view dynamic PET data, to derive dynamic and radiomic parameters from that data, and to combine dynamic data with radiomics ("dynomics"). The Imager-4D is available as a free download. This software has the potential to speed the adoption of advanced analysis of dynamic PET data into routine clinical use.

Prostate Specific Membrane Antigen Targeted 18F-DCFPyL Positron Emission Tomography/Computerized Tomography for the Preoperative Staging of High Risk Prostate Cancer: Results of a Prospective, Phase II, Single Center Study.

PURPOSE: We prospectively evaluated the diagnostic performance of prostate specific membrane antigen targeted 18F-DCFPyL positron emission tomography/computerized tomography in the preoperative staging of men at high risk for harboring metastatic prostate cancer despite a negative conventional staging evaluation. MATERIALS AND METHODS: Men with clinically localized high or very high risk prostate cancer were imaged with 18F-DCFPyL positron emission tomography/computerized tomography before undergoing radical prostatectomy with standardized pelvic lymph node dissection. The scans were interpreted by 2 blinded nuclear medicine readers and assessed for interreader variability as well as diagnostic accuracy for pelvic lymph node staging. Surgical pathology served as the reference standard to which 18F-DCFPyL scan findings were compared. RESULTS: A total of 25 men contributed analyzable data to this study. Seven of these patients (28%) were found to have 1 or more positive lymph nodes on surgical pathology. Sites of radiotracer uptake were identified in the prostate of all imaged patients. The 2 readers identified the same number of prostatic lesions in 22 patients (88%), of whom all had at least 1 intraprostatic lesion in common between the 2 reads. Additionally, the readers assigned the same N stage to 46 of 50 individual lymph node packets (92%). Following reconciliation of the relatively few discordant imaging reads, 7 patients (28%) were found to have 1 or more sites of radiotracer uptake in the pelvis consistent with N1 disease, resulting in 71.4% sensitivity (95% CI 29.0-96.3) and 88.9% specificity (95% CI 65.3-98.6). Analysis at the level of individual nodal packets resulted in 66.7% sensitivity (95% CI 29.9-92.5) and 92.7% specificity (95% CI 80.1-98.5). Three men (12%) had evidence of M1a disease. CONCLUSIONS: 18F-DCFPyL positron emission tomography/computerized tomography allowed for accurate detection of prostate cancer sites in men believed to have clinically localized disease based on conventional imaging. Our results support the need for a larger study to more precisely define the diagnostic accuracy of this novel molecular imaging test.

Nuclear Scintigraphy in Practice: Gastrointestinal Motility.

OBJECTIVE: The purpose of this article is to describe the clinical utility of state-of-theart gastrointestinal transit scintigraphy, including the standardized esophageal transit, solid and liquid gastric emptying, small-bowel transit, colon transit, and whole-gut transit scintigraphy, with an emphasis on procedure performance. CONCLUSION: Radionuclide gastrointestinal motility studies are noninvasive, quantitative, and physiologic diagnostic tools for evaluating patients with gastrointestinal complaints.

THE RELATIONSHIP OF BRAFV600E MUTATION STATUS TO FDG PET/CT AVIDITY IN THYROID CANCER: A REVIEW AND META-ANALYSIS.

OBJECTIVE: Papillary thyroid cancer (PTC) harboring a BRAFV600E gene mutation has been shown to exhibit aggressive tumor behavior and carries higher risks of recurrence and disease-specific death. In this systematic review and meta-analysis, we examined published evidence related to the accuracy of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detection of residual disease in patients with BRAFV600E mutated thyroid cancer. METHODS: We extracted data from PUBMED/MEDLINE and EMBASE published between January 1995 and March 2017. We included studies that compared FDG PET standardized uptake values (SUVs) between BRAFV600E-positive and BRAFV600E-negative subjects, as well as those that evaluated the odds of having FDG avidity between BRAFV600E-positive and -negative patients with thyroid cancer. RESULTS: There were a total of 12 studies in the systematic review. Seven studies qualified for the analysis for calculating the pooled odds ratio (OR). The pooled cohort with binary data had 1,144 patients out of which 843 were BRAFV600E positive and 301 were BRAFV600E negative. Those with a BRAFV600E mutation had a significantly greater likelihood of having FDG-avid lesions. The pooled OR was 2.12 (confidence interval [CI] 1.53-3.00, P<.01). The pooled mean SUV (cohort of 315 patients) was significantly higher in BRAFV600E-positive compared to BRAFV600E negative patients, with a pooled mean difference of 5.1 (CI 4.3-5.8). CONCLUSION: Our meta-analysis shows that presence of BRAFV600E mutation in PTC confers a higher likelihood of FDG PET avidity and is associated with higher SUV uptake values compared to BRAFV600E-mutation negative status. ABBREVIATIONS: BRAF = B-Raf proto-oncogene, serine/threonine kinase; CI = confidence interval; CT = computed tomography; DTC = differentiated thyroid cancer; FDG = fluorodeoxyglucose; PET = positron emission tomography; PTC = papillary thyroid cancer; SUV = standardized uptake value.

Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging.

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.

The Value of FDG PET/CT in Treatment Response Assessment, Follow-Up, and Surveillance of Lung Cancer.

OBJECTIVE: The purpose of this article is to summarize the evidence regarding the role of FDG PET/CT in treatment response assessment and surveillance of lung cancer and to provide suggested best practices. CONCLUSION: FDG PET/CT is a valuable imaging tool for assessing treatment response for patients with lung cancer, though evidence for its comparative effectiveness with chest CT is still evolving. FDG PET/CT is most useful when there is clinical suspicion or other evidence for disease recurrence or metastases. The sequencing, cost analysis, and comparative effectiveness of FDG PET/CT and conventional imaging modalities in the follow-up setting need to be investigated.

Prostate-specific Membrane Antigen: Interpretation Criteria, Standardized Reporting, and the Use of Machine Learning.

Prostate-specific membrane antigen targeting positron emission tomography (PSMA-PET) is routinely used for the staging and restaging of patients with various stages of prostate cancer. For clear communication with referring physicians and to improve inter-reader agreement, the use of standardized reporting templates is mandatory. Increasingly, tumor volume is used by reporting and response assessment frameworks to prognosticate patient outcome or measure response to therapy. However, the quantification of tumor volume is often too time-consuming in routine clinical practice. Machine learning-based tools can facilitate the quantification of tumor volume for improved outcome prognostication.

Positron Emission Tomography/Computed Tomography Transformation of Oncology: Multiple Myeloma.

This article provides a comprehensive review of the role of 2-deoxy-2-[18F]fluoro-d-glucose (18F FDG) positron emission tomography/computed tomography (PET/CT) in multiple myeloma (MM) and related plasma cell disorders. MM is a hematologic malignancy characterized by the neoplastic proliferation of plasma cells. 18F FDG PET/CT integrates metabolic and anatomic information, allowing for accurate localization of metabolically active disease. The article discusses the use of 18F FDG PET/CT in initial diagnosis, staging, prognostication, and assessing treatment response. Additionally, it provides valuable insights into the novel imaging targets including chemokine receptor C-X-C motif 4 and CD38.

FDG PET in a Patient on a GLP-1 Agonist/Insulin Secretagogue.

ABSTRACT: With the increase in use of GLP-1 receptor agonists such as semaglutide (Ozempic, Wegovy, Rybelsus) in the population, nuclear medicine physicians should be aware of the possibility of nondiagnostic FDG PET scans due to these medications, which work partly by increasing insulin secretion. We demonstrate a case where a patient's use of such a medication presumptively led to muscular and myocardial uptake, complicating scan interpretation considerably. Clinicians should be aware of the presence of these drugs and their potential effect on biodistribution in FDG PET. Further study is needed to best understand the effects of these medications on FDG biodistribution.