Evaluation of online teaching modules for PSMA PET interpretation.

PURPOSE: The proliferation of US FDA-approved prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging agents as a means to evaluate prostate cancer patients, and the expanding knowledge of interpretive pitfalls, has led to the generation of multiple online training modules geared toward the reading of each individual agent, each taking different approaches to criteria for interpretation, which may contribute to the variability of reporting in clinical practice. MATERIALS AND METHODS: The websites of the marketers of each FDA-approved agent [68Ga-PSMA-11 (Illuccix; Telix Pharmaceuticals), 68Ga-PSMA-11 (Locametz; Novartis Pharmaceuticals), 18F-rh-PSMA-7.3 (Posluma; Blue Earth Diagnostics)], and the website of the Society of Nuclear Medicine and Molecular Imaging [18F-DCFPyL (Pylarify)] were examined. All information pertaining to reader training, including videos, PDFs, and PowerPoint presentations, were reviewed. RESULTS: Videos from each module covered interpretive approach and pitfalls and ranged in length from a total of 20 min up to 315 min. Each module provided a different approach to PSMA PET scan findings, and on a different number and breadth of interpretive tips and pitfalls (a total of approximately 12-30 in all). CONCLUSIONS: Each of the four PSMA PET reader training modules covered important interpretive pitfalls. The lengths of the video portions of each module varied considerably, suggesting variable investments in time necessary to complete each module. The differences in the modules could contribute to inconsistency among readers depending on which module(s) they may have completed and which radiotracer(s) they are using.

Do myocardial PET-MR and PET-CT FDG images provide comparable information?

INTRODUCTION: Although positron emission tomography PET-MR imaging is emerging into clinical practice, many aspects of this imaging technique such as attenuation correction have yet to be validated for myocardial imaging. Thus, it is uncertain whether PET-MR FDG images provide clinical information which is comparable to PET-CT FDG images. The study goal was to systematically compare relative myocardial FDG concentrations obtained from cardiac PET-MR images to those derived from same day PET-CT images. METHODS: Myocardial FDG images of 27 patients undergoing PET-CT imaging, followed by PET-MR imaging 42 ± 13 minutes later as part of a prospective oncology study were analyzed. Mean segmental standardized uptake measurements (SUVmean) were obtained in each of the 17 standard myocardial segments and normalized to the brightest segment. RESULTS: Normalized segmental SUVmean values did not differ significantly between the PET-MR and PET-CT images (mean difference 0.002, P = .826). The specific segment was a marginally significant predictor of the differences (P = .057), with the largest difference in the anteroseptal basal segment. CONCLUSIONS: PET-MR, vis-à-vis PET-CT, does not significantly raise segmental uptake relative to the brightest segment, suggesting that PET-MR can be used similarly to PET-CT for applications where relative uptake is important.

Infectious Myocarditis on FDG-PET Imaging Mimicking Sarcoidosis.

Cardiac positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) is often used for the diagnosis of cardiac involvement in sarcoidosis. Areas of segmental perfusion defects coupled with FDG uptake are considered to represent active inflammation. However, these findings may be associated with other inflammatory myocardial diseases. We describe a case of tuberculous myocarditis with imaging findings mimicking those found in cardiac sarcoidosis.

Comparison of the prognostic value of regadenoson and adenosine myocardial perfusion imaging.

BACKGROUND: Regadenoson is now widely used in single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). However, the prognostic value of abnormal stress perfusion findings with regadenoson vs adenosine are unclear. The aim of this study was to evaluate the prognostic value of regadenoson SPECT and to compare it to that of adenosine SPECT. METHODS AND RESULTS: 3698 consecutive patients undergoing either adenosine or regadenoson SPECT were assessed at 1 year for the endpoints of cardiovascular death and a composite endpoint of cardiovascular death or MI. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for agent was used to account for differences in baseline characteristics. Patients undergoing adenosine SPECT MPI had a significantly higher prevalence of smoking history, diabetes, hypertension, and prior myocardial infarction (P < .05, all). At 1 year of follow-up, there were 154 cardiovascular deaths and 204 with the composite endpoint of cardiovascular death or MI. Using IPW adjustment to propensity for agent in a model with stress agent, summed stress score (SSS) remained a significant predictor of the composite endpoint of cardiovascular death or MI (HR 1.36 CI 1.28-1.46; P < .0001) as well as cardiovascular death (HR 1.38 CI 1.28-1.49; P < .0001). The interaction of SSS with agent was not significant. Similar findings were seen with summed difference score (SDS). CONCLUSIONS: SSS derived from either adenosine or regadenoson SPECT MPI is a significant predictor of events and provides incremental prognostic information beyond basic clinical variables. We have shown for the first time that use of regadenoson vs adenosine as stress agent does not modify the prognostic significance of SSS. Similar findings were seen with SDS.

Radiographic Response Assessments and Standardized Imaging Interpretation Criteria in Head and Neck Cancer on FDG PET/CT: A Narrative Review.

INTRODUCTION: There is growing interest in the development and application of standardized imaging criteria (SIC), to minimize variability and improve the reproducibility of image interpretation in head and neck squamous cell carcinoma (HNSCC). METHODS: "Squamous cell carcinoma" AND "standardized interpretation criteria" OR "radiographic response assessment" were searched using PubMed and Google Scholar for articles published between 2009 and 2024, returning 56 publications. After abstract review, 18 were selected for further evaluation, and 6 different SICs (i.e., PERCIST, Porceddu, Hopkins, NI-RADS, modified Deauville, and Cuneo) were included in this review. Each SIC is evaluated in the context of 8 desired traits of a standardized reporting system. RESULTS: Two SICs have societal endorsements (i.e., PERCIST, NI-RADS); four can be used in the evaluation of locoregional and systemic disease (i.e., PERCIST, Hopkins, NI-RADS, Cuneo), and four have specific categories for equivocal imaging results (i.e., Porceddu, NI-RADS, modified Deauville, and Cuneo). All demonstrated areas for future improvement in the context of the 8 desired traits. CONCLUSION: Multiple SICs have been developed for and demonstrated value in HNSCC post-treatment imaging; however, these systems remain underutilized. Selecting an SIC with features that best match the needs of one's practice is expected to maximize the likelihood of successful implementation.

The cutting edge: Promising oncology radiotracers in clinical development.

Molecular imaging moves forward with the development of new imaging agents, and among these are new radiotracers for nuclear medicine applications, particularly positron emission tomography (PET). A number of new targets are becoming accessible for use in oncologic applications. In this review, major new radiotracers in clinical development are discussed. Prominent among these is the family of fibroblast-activation protein-targeted agents that interact with the tumor microenvironment and may show superiority to 2-deoxy-2-[18F]fluoro-d-glucose in a subset of different tumor histologies. Additionally, carbonic anhydrase IX (CAIX) inhibitors are directed at clear cell renal cell carcinoma, which has long lacked an effective PET imaging agent. Those CAIX agents may also have utility in hypoxic tumors. Pentixafor, which binds to a transmembrane receptor, may similarly allow for visualization by PET of low-grade lymphomas, as well as being a second agent for multiple myeloma that opens theranostic possibilities. There are new adrenergic agents aimed at providing a PET-visible replacement to the single-photon-emitting radiotracer meta-[123I]iodobenzylguanidine (MIBG). Finally, in response to a major development in oncologic chemotherapy, there are new radiotracers targeted at assessing the suitability or use of immunotherapeutic agents. All of these and the existing evidence for their utility are discussed.

Molecular imaging for non-invasive risk stratification of renal masses.

Anatomic imaging with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) has long been the mainstay of renal mass characterization. However, those modalities are often unable to adequately characterize indeterminate, solid, enhancing renal masses - with some exceptions, such as the development of the clear-cell likelihood score on multi-parametric MRI. As such, molecular imaging approaches have gained traction as an alternative to anatomic imaging. Mitochondrial imaging with 99mTc-sestamibi single-photon emission computed tomography/CT is a cost-effective means of non-invasively identifying oncocytomas and other indolent renal masses. On the other end of the spectrum, carbonic anhydrase IX agents, most notably the monoclonal antibody girentuximab - which can be labeled with positron emission tomography radionuclides such as zirconium-89 - are effective at identifying renal masses that are likely to be aggressive clear cell renal cell carcinomas. Renal mass biopsy, which has a relatively high non-diagnostic rate and does not definitively characterize many oncocytic neoplasms, nonetheless may play an important role in any algorithm targeted to renal mass risk stratification. The combination of molecular imaging and biopsy in selected patients with other advanced imaging methods, such as artificial intelligence/machine learning and the abstraction of radiomics features, offers the optimal way forward for maximization of the information to be gained from risk stratification of indeterminate renal masses. With the proper application of those methods, inappropriately aggressive therapy for benign and indolent renal masses may be curtailed.

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.

Fluoroestradiol PET-MRI imaging for detection of endometriosis lesions and symptom correlation.

Endometriosis is a common cause of infertility, pelvic pain, and dysmenorrhea and there are prior case reports of lesion detection using an 18F-fluoroestradiol (FES) tracer with positron emission tomography (PET). We aimed to further investigate the use of the FES tracer in the context of PET-magnetic resonance (PET-MR) imaging. We administered FES to 6 patients and then imaged them using a Siemens mMR PET-MR scanner. Each patient was taken to surgery within 30 days after imaging, and surgical visualization served as the gold-standard for diagnosis. PET did not prove to be as sensitive as MR (50% per-patient sensitivity versus 67% per-patient and 35% versus 48% per-lesion), and did not show any additional sites over and above MR. When MR was used to localize lesions on PET after imaging, there was insufficient evidence of an association between total tracer uptake and reported pain intensity (P=0.25). FES PET-MR offers no additional value to MR for endometriosis.

PSMA-Targeted Radiopharmaceuticals for Prostate Cancer Diagnosis and Therapy.

ABSTRACT: Prostate cancer (PCa) is the most common noncutaneous malignancy in men. Until recent years, accurate imaging of men with newly diagnosed PCa, or recurrent or low-volume metastatic disease, was limited. Further, therapeutic options for men with advanced, metastatic, castration-resistant disease were increasingly limited as a result of increasing numbers of systemic therapies being combined in the upfront metastatic setting. The advent of urea-based, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) has partially addressed those shortcomings in diagnosis and therapy of PCa. On the diagnostic side, there are multiple pivotal phase III trials with several different agents having demonstrated utility in the initial staging setting, with generally modest sensitivity but very high specificity for determining otherwise-occult pelvic nodal involvement. That latter statistic drives the utility of the scan by allowing imaging interpreters to read with very high sensitivity while maintaining a robust specificity. Other pivotal phase III trials have demonstrated high detection efficiency in patients with biochemical failure, with high positive predictive value at the lesion level, opening up possible new avenues of therapy such as metastasis-directed therapy. Beyond the diagnostic aspects of PSMA-targeted radiotracers, the same urea-based chemical scaffolds can be altered to deliver therapeutic isotopes to PCa cells that express PSMA. To date, one such agent, when combined with best standard-of-care therapy, has demonstrated an ability to improve overall survival, progression-free survival, and freedom from skeletal events relative to best standard-of-care therapy alone in men with metastatic, castration-resistant PCa who are post chemotherapy. Within the current milieu, there are a number of important future directions including the use of artificial intelligence to better leverage diagnostic findings, further medicinal chemistry refinements to the urea-based structure that may allow improved tumor targeting and decreased toxicities, and the incorporation of new radionuclides that may better balance efficacy with toxicities than those nuclides that are available.

Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis.

PURPOSE: Endometriosis is an estrogen-dependent disorder of menstruating primates where tissues similar to the inner lining of the uterus exist "ectopically" outside of the uterus. The ectopic endometrium, like the endometrium within the uterus, expresses estrogen receptors (ER) and progesterone receptors (PR) and undergoes hormone-dependent cell proliferation and bleeding each menstrual cycle. The goal of this study was to conduct abdominopelvic positron emission tomography (PET) scans with computed tomography (CT) imaging of rhesus macaques (Macaca mulatta) using radiotracers that target ER and PR [16α-[18F]fluoroestradiol (FES) and 12-[18F]fluoro-furanyl-nor-progesterone (FFNP)] in individuals with and without endometriosis. We also aimed to determine if menstrual cycle phase and/or the presence of endometriosis affected the uptake of these radiotracers. PROCEDURES: Rhesus macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent PET/CT scans with FES. A subset of the animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVs) were obtained for each radiotracer in target and background tissues (e.g., intestinal). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state. RESULTS: Abdominopelvic PET/CT could not resolve small, individual endometriotic lesions. However, macaques with endometriosis displayed higher uterine uptake compared to those without the disorder. Radiotracer uptake differed by menstrual cycle phase with increased uterine uptake of both radiotracers in the proliferative phase of the menstrual cycle. Background intestinal uptake of FFNP increased over time after infusion, but only during the proliferative phase. CONCLUSIONS: PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

Imaging of Chromophobe Renal Cell Carcinoma with 99mTc-Sestamibi SPECT/CT: Considerations Regarding Risk Stratification and Histologic Reclassification.

PURPOSE: Indeterminate renal masses are increasingly incidentally found on cross-sectional imaging. 99mTc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) scans can be used to identify oncocytomas and oncocytic renal neoplasms, including a subset of chromophobe renal cell carcinomas (chRCCs), which are viewed as false-positive. PROCEDURE: Patients imaged with renal sestamibi scans between 2014 and 2023 were reviewed. Those patients with solitary tumors that were originally classified as chRCC were included in the analysis. Imaging with SPECT/CT from the liver dome down had been carried out 75 min after the administration of 925 MBq of 99mTc-sestamibi. All available H&E and immunostained slides were re-reviewed and classified according to WHO 2022 criteria. Confirmatory immunohistochemical stains were performed in tumors considered morphologically suspicious for non-chRCC entities. RESULT: A total of 18 patients with solitary tumors were included in the final analysis. 13/18 (72.2%) tumors in this cohort remained classified as chRCC, with 4/18 (22.2%) being eosinophilic-variant chRCC. The reclassified tumors (5/18 [27.8%]) included 2/18 (11.1%) low-grade oncocytic tumor (LOT), 1/18 (5.5%) eosinophilic vacuolated tumor (EVT), and 2/18 (11.1%) unclassified low-grade oncocytic neoplasms. As such, only 2/9 (22.2%) qualitatively "hot" tumors were chRCC other than eosinophilic-variant and only 1/9 (11.1%) "cold" tumors was a histology other than chRCC. CONCLUSION: Based on current histopathologic classification methods, it is likely that the "false-positive" rate of uptake on renal sestamibi scans with chRCC has been over-stated. Further study is warranted to better refine the optimal utility of renal sestamibi scans for non-invasive risk stratification of indeterminate renal masses.

PET/Computed Tomography Transformation of Oncology: Kidney and Urinary Tract Cancers.

Renal cell carcinoma (RCC) and urothelial carcinoma (UC) are two of the most common genitourinary malignancies. 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) can play an important role in the evaluation of patients with RCC and UC. In addition to the clinical utility of 18F-FDG PET to evaluate for metastatic RCC or UC, the shift in molecular imaging to focus on specific ligand-receptor interactions should provide novel diagnostic and therapeutic opportunities in genitourinary malignancies. In combination with the rise of artificial intelligence, our ability to derive imaging biomarkers that are associated with treatment selection, response assessment, and overall patient prognostication will only improve.

Comparison of Multiple Segmentation Methods for Volumetric Delineation of Primary Prostate Cancer with Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT.

This study aimed to assess the accuracy of intraprostatic tumor volume measurements on prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT made with various segmentation methods. An accurate understanding of tumor volumes versus segmentation techniques is critical for therapy planning, such as radiation dose volume determination and response assessment. Methods: Twenty-five men with clinically localized, high-risk prostate cancer were imaged with 18F-DCFPyL PET/CT before radical prostatectomy. The tumor volumes and tumor-to-prostate ratios (TPRs) of dominant intraprostatic foci of uptake were determined using semiautomatic segmentation (applying SUVmax percentage [SUV%] thresholds of SUV30%-SUV70%), adaptive segmentation (using adaptive segmentation percentage [A%] thresholds of A30%-A70%), and manual contouring. The histopathologic tumor volume (TV-Histo) served as the reference standard. The significance of differences between TV-Histo and PET-based tumor volume were assessed using the paired-sample Wilcoxon signed-rank test. The Spearman correlation coefficient was used to establish the strength of the association between TV-Histo and PET-derived tumor volume. Results: Median TV-Histo was 2.03 cm3 (interquartile ratio [IQR], 1.16-3.36 cm3), and median TPR was 10.16%. The adaptive method with an A40% threshold most closely determined the tumor volume, with a median difference of +0.19 (IQR, -0.71 to +2.01) and a median relative difference of +7.6%. The paired-sample Wilcoxon test showed no significant difference in PET-derived tumor volume and TV-Histo using A40%, A50%, SUV40%, and SUV50% threshold segmentation algorithms (P > 0.05). For both threshold-based segmentation methods, use of higher thresholds (e.g., SUV60% or SUV70% and A50%-A70%) resulted in underestimation of tumor volumes, and use of lower thresholds (e.g., SUV30% or SUV40% and A30%) resulted in overestimation of tumor volumes relative to TV-Histo and TPR. Manual segmentation overestimated the tumor volume, with a median difference of +2.49 (IQR, 0.42-4.11) and a median relative difference of +130%. Conclusion: Segmentation of intraprostatic tumor volume and TPR with an adaptive segmentation approach most closely approximates TV-Histo. This information might be used to guide the primary treatment of men with clinically localized, high-risk prostate cancer.

One institutions' experience with a true standard 15 mCi dose of I-131 for the treatment of Graves' disease.

INTRODUCTION: Currently, there is a lack of consensus on the fixed dosage of RAI to be administered for this purpose between the main guideline frameworks set forth by the American Thyroid Association (ATA), Society of Nuclear Medicine and Molecular Imaging (SNMMI), European Association of Nuclear Medicine (EANM) and the European Thyroid Association (ETA). In this retrospective study, we will investigate the effectiveness of using a standard dose of 15 mCi ±10% of RAI in the treatment of Graves'. METHODS: A retrospective chart review was conducted for the period between 1 May 2014 and 2 September 2020, to identify patients diagnosed with hyperthyroidism due to Graves' disease. The patients were grouped based on outcome and assessed for the efficacy of the dosage of 15 mCi ±10% of RAI in a successful treatment. RESULTS: Sixty-seven patients were identified that met the inclusion criteria between 1 May 2014 and 2 September 2020. Of the 67 RAI ablations; 60 patients became hypothyroid [60/67, (89.55%)], 2 euthyroid [2/67, (2.99%)] and 5 remained hyperthyroid [5/67, (7.46%)]. CONCLUSIONS: For the treatment of Graves' disease, the use of a standard low dose of 15 mCi ±10% has a high success rate without additional measurements or calculations beyond a standard planar image and 24-h uptake %. The adoption of a standard low dose of 15 mCi of I-131 across institutional guidelines would streamline dosage questions and eliminate the need to determine the weight of the thyroid for calculations in all RAI treatments for hyperthyroidism caused by Graves' disease.

Near-Peer Teaching in Radiology Symposia: A Success Story in Residents as Teachers.

INTRODUCTION: Peer learning and near-peer teaching have been described in many specialties, less so in Radiology. We present near-peer teaching whereby residents present a series of didactic sessions at the course outset in the form of "symposia" and perform a scholarly activity in the form of teaching. We aim to demonstrate how near-peer teaching in symposia front-loaded within an introductory radiology course can improve medical student satisfaction. METHOD: A total of 169 students were enrolled over a period of 3 years, 55 before (2017-2018) and 114 (2018-2020) after the introduction of the symposium. Anonymous course evaluations were collected from all students. In addition, 240 fourth-year medical students who also attended symposium lectures received satisfaction surveys in 2019 and 2020. RESULTS: All (169/169, 100%) students taking the course evaluated it. Overall evaluation scores rose from 8.3/10 to 9.0/10 post-symposia. Among student satisfaction surveys, 89/240 (37%) specifically commented on symposia; 91% (80/89) of those found symposia very or extremely informative. 29/71 (41%) of all residents were able to participate in the symposia, 20/29 in multiple years throughout residency, allowing them to fulfill the Accreditation Council for Graduate Medical Education interpersonal and communication skills core competencies and meet scholarly activity requirements. CONCLUSION: Near-peer teaching in the form of resident-taught interactive didactics grouped in symposia can have a positive outcome on medical student satisfaction.

Uterine uptake of estrogen and progestogen-based radiotracers in rhesus macaques with endometriosis.

Purpose: Few investigations have examined the uptake of radiotracers that target the prominent sex-steroid receptors in the uterus across the menstrual cycle and with disease state. We aimed to determine if uptake of the radiotracers that target estrogen and progesterone receptors (ER and PR) differ with the presence of endometriosis and/or across the menstrual cycle. We performed PET and computed tomography (CT) imaging procedures on rhesus macaques (Macaca mulatta) using 16α-[18F]fluoroestradiol (FES) and 21-[18F]fluoro-furanyl-nor-progesterone (FFNP) in individuals with and without endometriosis in the proliferative and secretory phases of the menstrual cycle. Procedures: Macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent abdominopelvic PET/CT scans with FES. A subset of these animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVbw) were obtained for each radiotracer in target and background tissues (i.e., intestinal and muscle). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state. Results: PET/CT could not resolve small, individual endometriotic lesions. However, uterine uptake of both radiotracers was elevated in the proliferative phase compared to the secretory phase of the menstrual cycle. Intestinal uptake exhibited greater variation during the proliferative phase compared to the secretory phase. Further, intestinal uptake of FFNP increases as the scan progresses, but only during the proliferative phase. Muscle uptake did not differ with menstrual phase or radiotracer type. Lastly, macaques with endometriosis displayed higher uterine uptake of FES compared to those without endometriosis. Conclusions: PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

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.

Increased tryptophan, but not increased glucose metabolism, predict resistance of pembrolizumab in stage III/IV melanoma.

Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov, NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n = 68). Melanoma cell-specific TPH1 and LAT1 expressions were significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cutpoint survival analysis of pretreatment 'high' vs. 'low' C11-AMT SUVmax of the hottest tumor lesion per patient revealed that the 'low' C11-AMT SUVmax was associated with longer progression-free survival in our clinical trial (n = 26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.

Incidental renal masses on SPECT/CT and PET/CT.

While the presence of incidental breast and lung masses on cardiac scans is well known, renal masses are often incidentally discovered as well on cardiac examinations, some of which are malignant. We searched the electronic medical record system over the past 18 years, since the system was installed, for patients with a cardiac rubidium-82 (82Rb) rubidium PET/CT or technetium-99m (99mTc) sestamibi SPECT/CT performed within 1 year of a renal-protocol CT or MR. Each PET/CT or SPECT/CT was examined for presence of a renal lesion on the attenuation-correction CT images. We found 43 SPECT/CT and 18 PET/CT studies which fit the desired criteria. Of these, 7 SPECT/CT studies and 2 PET/CT studies demonstrated the renal mass on at least one of the two sets of CT images (rest or stress); if not visible, most commonly the tumor was either out of the field of view or had already been removed. Of these, 6 SPECT/CT and 2 PET/CT studies demonstrated a malignancy. Cardiac SPECT/CT and PET/CT images demonstrate incidental renal masses with a non-negligible frequency, and CT images should be carefully examined.