Surveillance prostate biopsy utilizing piflufolastat F 18-PET/CT targeting in the intact prostate - A case report.

75-year-old patient with cochlear implant diagnosed with very low risk prostate cancer (PSA 6.44 ng/mL, and Grade Group 1 (left apical core)) managed on Active Surveillance (AS). After four years monitoring on AS, PSA was observed to increase to 10.84 and patient was reevaluated for disease progression. Due to cochlear implant, multiparametric MRI was not an imaging option and patient was referred for piflufolastat F 18-PET/CT. In addition to previously identified left sided lesion, tracer uptake was observed within the posterior transition and peripheral zone of the right lobe of the prostate, which ultimately confirmed disease progression on targeted biopsy.

Prospective Pilot Study of 18F-Fluoroestradiol PET/CT in Patients With Invasive Lobular Carcinomas.

BACKGROUND. PET/CT with 18F-fluoroestradiol (FES) (FDA-approved in 2020) depicts tissues expressing estrogen receptor (ER). Invasive lobular carcinoma (ILC) is commonly ER positive. OBJECTIVE. The primary aim of this study was to assess the frequency with which sites of histologically proven ILC have abnormal uptake on FES PET/CT. METHODS. This prospective single-center pilot study, conducted from December 2020 to August 2021, enrolled patients with histologically confirmed ILC to undergo FES PET/CT; patients optionally underwent FDG PET/CT. Two nuclear radiologists assessed FES PET/CT and FDG PET/CT studies for abnormal uptake corresponding to known ILC sites at enrollment and for additional sites of abnormal uptake, resolving differences by consensus. The primary endpoint was percentage of known ILC sites showing abnormal FES uptake. The alternative to the null hypothesis was that more than 60% of sites would have abnormal FES uptake, exceeding the percentage of ILC with abnormal FDG uptake described in prior literature. A sample size of 24 biopsied lesions was preselected to provide 81% power for the alternative hypothesis (one-sided α = .10). Findings on FES PET/CT and FDG PET/CT were summarized for additional secondary endpoints. RESULTS. The final analysis included 17 patients (mean age, 59.1 ± 13.2 years) with 25 sites of histologically confirmed ILC at enrollment (22 breast lesions, two axillary lymph nodes, one distant metastasis). FES PET/CT showed abnormal uptake in 22 of 25 (88%) lesions, sufficient to reject the null hypothesis (p = .002). Thirteen patients underwent FDG PET/CT. Four of 23 (17%) sites of histologically confirmed ILC, including additional sites detected and confirmed after enrollment, were identified with FES PET/CT only, and 1 of 23 (4%) was identified only with FDG PET/CT (p = .18). FES PET/CT depicted additional lesions not detected with standard-of-care evaluation in 4 of 17 (24%) patients (two contralateral breast cancers and two metastatic axillary lymph nodes, all with subsequent histologic confirmation). Use of FES PET/CT resulted in changes in clinical stage with respect to standard-of-care evaluation in 3 of 17 (18%) patients. CONCLUSION. The primary endpoint of the trial was met. The frequency of abnormal FES uptake among sites of histologically known ILC was found to be to be significantly greater than 60%. CLINICAL IMPACT. This pilot study shows a potential role of FES PET/CT in evaluation of patients with ILC. TRIAL REGISTRATION. ClinicalTrials.gov NCT04252859.

PET-CT in Clinical Adult Oncology: I. Hematologic Malignancies.

PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging and evaluation of suspected recurrence. The goal of this 6-part series of review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for the more common adult malignancies. In the first article of this series, hematologic malignancies are addressed. The classification of these malignancies will be outlined, with the disclaimer that the classification of lymphomas is constantly evolving. Critical applications, potential pitfalls, and nuances of PET-CT imaging in hematologic malignancies and imaging features of the major categories of these tumors are addressed. Issues of clinical importance that must be reported by the imaging professionals are outlined. The focus of this article is on [18F] fluorodeoxyglucose (FDG), rather that research tracers or those requiring a local cyclotron. This information will serve as a resource for the appropriate role and limitations of PET-CT in the clinical management of patients with hematological malignancy for health care professionals caring for adult patients with hematologic malignancies. It also serves as a practical guide for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

PET-CT in Clinical Adult Oncology-VI. Primary Cutaneous Cancer, Sarcomas and Neuroendocrine Tumors.

PET-CT is an advanced imaging modality with many oncologic applications, including staging, therapeutic assessment, restaging and surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, the potential pitfalls and nuances that characterize these applications, and guidelines for image interpretation. Tumor-specific clinical information and representative PET-CT images are provided. The current, sixth article in this series addresses PET-CT in an evaluation of aggressive cutaneous malignancies, sarcomas and neuroendocrine tumors. A discussion of the role of FDG PET for all types of tumors in these categories is beyond the scope of this review. Rather, this article focuses on the most common malignancies in adult patients encountered in clinical practice. It also focuses on Food and Drug Agency (FDA)-approved and clinically available radiopharmaceuticals rather than research tracers or those requiring a local cyclotron. This information will serve as a guide to primary providers for the appropriate role of PET-CT in managing patients with cutaneous malignancies, sarcomas and neuroendocrine tumors. The nuances of PET-CT interpretation as a practical guide for imaging providers, including radiologists, nuclear medicine physicians and their trainees, are also addressed.

PET-CT in Clinical Adult Oncology-IV. Gynecologic and Genitourinary Malignancies.

Concurrently acquired positron emission tomography and computed tomography (PET-CT) is an advanced imaging modality with diverse oncologic applications, including staging, therapeutic assessment, restaging and longitudinal surveillance. This series of six review articles focuses on providing practical information to providers and imaging professionals regarding the best use and interpretative strategies of PET-CT for oncologic indications in adult patients. In this fourth article of the series, the more common gynecological and adult genitourinary malignancies encountered in clinical practice are addressed, with an emphasis on Food and Drug Administration (FDA)-approved and clinically available radiopharmaceuticals. The advent of new FDA-approved radiopharmaceuticals for prostate cancer imaging has revolutionized PET-CT imaging in this important disease, and these are addressed in this report. However, [18F]F-fluoro-2-deoxy-d-glucose (FDG) remains the mainstay for PET-CT imaging of gynecologic and many other genitourinary malignancies. This information will serve as a guide for the appropriate role of PET-CT in the clinical management of gynecologic and genitourinary cancer patients for health care professionals caring for adult cancer patients. It also addresses the nuances and provides guidance in the accurate interpretation of FDG PET-CT in gynecological and genitourinary malignancies for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

PET-CT in Clinical Adult Oncology: III. Gastrointestinal Malignancies.

PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging and longitudinal surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, and the potential pitfalls and nuances that characterize these applications. In the third of these review articles, key tumor-specific clinical information and representative PET-CT images are provided to outline the role that PET-CT plays in the management of patients with gastrointestinal malignancies. The focus is on the use of 18F fluorodeoxyglucose (FDG), rather than on research radiopharmaceuticals under development. Many different types of gastrointestinal tumors exist, both pediatric and adult. A discussion of the role of FDG PET-CT for all of these is beyond the scope of this review. Rather, this article focuses on the most common adult gastrointestinal malignancies that may be encountered in clinical practice. The information provided here will provide information outlining the appropriate role of PET-CT in the clinical management of patients with gastrointestinal malignancies for healthcare professionals caring for adult cancer patients. It also addresses the nuances and provides interpretive guidance related to PET-CT for imaging providers, including radiologists, nuclear medicine physicians and their trainees.

PET-CT in Clinical Adult Oncology: II. Primary Thoracic and Breast Malignancies.

Positron emission tomography combined with x-ray computed tomography (PET-CT) is an advanced imaging modality with oncologic applications that include staging, therapy assessment, restaging, and surveillance. This six-part series of review articles provides practical information to providers and imaging professionals regarding the best use of PET-CT for the more common adult malignancies. The second article of this series addresses primary thoracic malignancy and breast cancer. For primary thoracic malignancy, the focus will be on lung cancer, malignant pleural mesothelioma, thymoma, and thymic carcinoma, with an emphasis on the use of FDG PET-CT. For breast cancer, the various histologic subtypes will be addressed, and will include 18F fluorodeoxyglucose (FDG), recently Food and Drug Administration (FDA)-approved 18F-fluoroestradiol (FES), and 18F sodium fluoride (NaF). The pitfalls and nuances of PET-CT in breast and primary thoracic malignancies and the imaging features that distinguish between subcategories of these tumors are addressed. This review will serve as a resource for the appropriate roles and limitations of PET-CT in the clinical management of patients with breast and primary thoracic malignancies for healthcare professionals caring for adult patients with these cancers. It also serves as a practical guide for imaging providers, including radiologists, nuclear medicine physicians, and their trainees.

PET-CT in Clinical Adult Oncology-V. Head and Neck and Neuro Oncology.

PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging, and longitudinal surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, and the potential pitfalls and nuances that characterize these applications. In addition, key tumor-specific clinical information and representative PET-CT images are provided to outline the role that PET-CT plays in the management of oncology patients. Hundreds of different types of tumors exist, both pediatric and adult. A discussion of the role of FDG PET for all of these is beyond the scope of this review. Rather, this series of articles focuses on the most common adult malignancies that may be encountered in clinical practice. It also focuses on FDA-approved and clinically available radiopharmaceuticals, rather than research tracers or those requiring a local cyclotron. The fifth review article in this series focuses on PET-CT imaging in head and neck tumors, as well as brain tumors. Common normal variants, key anatomic features, and benign mimics of these tumors are reviewed. The goal of this review article is to provide the imaging professional with guidance in the interpretation of PET-CT for the more common head and neck malignancies and neuro oncology, and to inform the referring providers so that they can have realistic expectations of the value and limitations of PET-CT for the specific type of tumor being addressed.

Seeking an optimal dose of preoperative corticosteroids in chronic rhinosinusitis with nasal polyposis: A randomized controlled trial.

BACKGROUND: Preoperative corticosteroids have been shown to improve surgical visibility and intraoperative blood loss for chronic rhinosinusitis with nasal polyposis (CRSwNP) patients undergoing endoscopic sinus surgery (ESS). However, there is no consensus on the optimal dosing regimen. METHODS: A randomized, controlled trial was conducted to compare low, medium, and high dose corticosteroids prior to ESS. Patients with CRSwNP refractory to medical management were randomized to low (N = 8), medium (N = 10), or high (N = 5) dosing regimens of corticosteroids prior to ESS. Baseline disease severity was measured with the 22-item Sino-nasal Outcome Test and Lund-Mackay scores. Modified Lund-Kennedy endoscopic scores (MLKES) were measured at baseline and after corticosteroid treatment. Intraoperative parameters were measured including Boezaart surgical visibility score, intraoperative blood loss, and operative time. RESULTS: Medium dose corticosteroids demonstrated a superior surgical visibility score to low dose and comparable results to high dose, but these results were not significant (p = 0.33). No significant difference was observed between groups for total blood loss (p = 0.15), operative time (p = 0.87), or change in MLKES (p = 0.27). CONCLUSIONS: Current recommendations include the use of preoperative corticosteroids in patients with CRSwNP undergoing ESS, but there is no consensus on dose or duration. We did not find a statistically significant difference in surgical field visibility, intraoperative blood loss, or operative time between different dosing regimens. Further studies are needed to evaluate the efficacy of a low-dose preoperative regimen with the goal of reducing cumulative patient exposure to systemic corticosteroids.

Pineal Gland Metastasis From Gastric Carcinoid-A Rare Manifestation.

ABSTRACT: Pineal region metastases are very rare, occurring in 0.4% to 3.8% of patients with solid tumors and most frequently arise from a lung cancer primary tumor. We present a case of a 67-year-old man with a gastric well-differentiated neuroendocrine tumor (NET) metastatic to the pineal gland identified on 68Ga-DOTATATE PET/CT imaging followed by MRI confirmation. To our knowledge, this is the third NET case to be reported in the literature with such presentation and first case to be described on 68Ga-DOTATATE PET/CT. A case of metastatic bronchial NET as well as a case of metastatic esophageal NET to the pineal gland were reported previously.

An Overview of Selected Rare B-Cell Lymphoproliferative Disorders: Imaging, Histopathologic, and Clinical Features.

Lymphoproliferative disorders (LPD) are conditions characterized by the uncontrolled proliferation of B or T-cell lines. They encompass a wide spectrum of abnormalities, which may be broadly classified as reactive processes or malignant diseases, such as lymphoma, based on their cellular clonality and clinical behavior. While some of these disorders are rare, they may be encountered sporadically in clinical practice, causing diagnostic dilemmas owing to overlap in their clinical and imaging features with more common disorders. The updated 4th edition WHO classification of lymphoid neoplasms was released in 2016 to incorporate the rapid clinical, pathological, molecular biology and cytogenetic advances of some of these disorders. Despite these updates, very little information is presented in the literature from the radiology perspective. The aim of this article is to familiarize radiologists and other physicians with certain rare variants of B-cell lymphoproliferative disorders with a focus on imaging features of these disorders, as well as to provide an overview of some important updates contained within the new WHO classification of lymphoid neoplasms.

Correlation between FDG-PET uptake and survival in patients with primary brain tumors.

This study evaluates F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) semi-quantitative analysis as biomarker of tumor aggressiveness and predictor of survival in patients with primary brain tumors. Semi-quantitative analyses (SUVmax, SUVmean) were derived from FDG PET images in 78 patients with suspected recurrence of primary brain tumors based on MRI. SUVmax and the ratio of lesion SUVmax to the SUVmean of contralateral white matter (SUVmax/WM) were measured. A one-way Analysis of Variance (ANOVA), Kaplan-Meier analyses and the log rank test for evaluating statistical significance were utilized. There was statistical significance for time between FDG-PET and patient death. There was a significant difference with respect to FDG-PET time to death between patients with glioblastoma and patients with anaplastic oligodendroglioma, oligodendroglioma, and other histological subtypes. There is significant correlation with SUVmax/WM and patient survival following FDG-PET when a cut-point ratio of 1.90 is used. A 1.90 cut-point ratio of SUVmax/WM was associated with a difference in survival. GBM was associated with a significant difference in terms of reduced survival following FDG PET compared to most other histological sub-types. These results may inform current treatment and counseling strategies for patients with primary brain tumors.

18F-fluciclovine PET CT detection of biochemical recurrent prostate cancer at specific PSA thresholds after definitive treatment.

OBJECTIVES: To evaluate various Prostate-Specific Antigen (PSA) thresholds at which a 18F-fluciclovine PET scan could be considered in the setting of biochemical recurrent prostate cancer after definitive treatment. METHODS: We analyzed available records of men who underwent a 18F-fluciclovine PET scan after definitive therapy at a single academic institution between November 2016 to May 2018. The primary outcome was the rate of positive imaging findings at specific PSA thresholds. We then employed empiric strategies including a ROC curve and decision curve analysis to identify a specific threshold for which obtaining a positive result would be optimized. RESULTS: A total of 115 men underwent imaging with 18F-fluciclovine PET. No concerning lesions were identified in 25 (21.7%) patients, 32 (27.8%) had a solitary lesion identified, 45 (39.1%) had 2 to 5 lesions, and 13 (11.3%) had greater than 5 suspicious lesions identified. At PSA thresholds of less than 0.5, 0.5 to 2.0, and greater than 2, lesions were detected in 55.5% (12/22), 70.6% (24/34), and 91.5% (54/59) of patients respectively [P < 0.001]. Our ROC analysis yielded a PSA threshold of 2.10 while our decision curve analysis provided a PSA cutoff of 1.38. CONCLUSION: This study constitutes an early single institution series evaluating the use of 18F-fluciclovine PET scans in the assessment of biochemically recurrent prostate cancer after definitive treatment. The probability of having positive imaging findings and increasing numbers of suspicious lesions rises with increasing PSA. Utilization of a lower PSA threshold of 0.5 may allow earlier intervention with salvage therapies in biochemical recurrence. However, using a threshold below 1 carries a higher risk of negative scans. Employing a higher PSA threshold of 1 to 2 carries greater sensitivity and specificity and may maximize identifying individuals with early BCR who may benefit from early intervention, while minimizing negative scans.

Prospective Evaluation of Bone Metabolic Markers as Surrogate Markers of Response to Radium-223 Therapy in Metastatic Castration-resistant Prostate Cancer.

PURPOSE: Radium-223 is approved for metastatic castration-resistant prostate cancer (mCRPC) based on improved overall survival, and delay in skeletal related events. However, it is not associated with PSA or radiographic response, which poses a challenge in real-time assessment of its efficacy. Surrogate markers of treatment outcomes may facilitate tailoring treatment duration with radium-223, by limiting the duration of therapy with radium-223 in these patients. Here, we sought to investigate the utility of bone metabolic markers (BMMs) as surrogate markers of response to radium-223 in mCRPC. PATIENTS AND METHODS: A prospective phase II trial of radium-223 plus enzalutamide (RE) versus enzalutamide alone was designed to assess surrogacy of BMMs with respect to response to radium-223. Enzalutamide was used as a comparator in lieu of placebo due to the progressive disease. Co-primary endpoints were relative change in serum BMM N-telopeptide (NTP) levels from baseline to 6 months between the two arms and safety and feasibility of the combination. RESULTS: Thirty-nine men were randomized to RE (n = 27) or enzalutamide (n = 12). Combination was safe and feasible. Primary endpoint was met. A statistically significant relative change to NTP ratios between arms (0.64, 95% confidence interval, 0.51-0.81; P = 0.00048) favored RE versus enzalutamide. Overall, BMMs decreased with the RE therapy compared with enzalutamide. Improved PSA response rate in RE versus enzalutamide (P = 0.024), correlated with decline in BMMs. CONCLUSIONS: BMMs declined significantly with combination therapy, and were associated with improved outcomes. Upon external validation, BMMs may emerge as surrogate markers to monitor treatment with radium-223 in real-time.

Anti-inflammatory agent, OKN-007, reverses long-term neuroinflammatory responses in a rat encephalopathy model as assessed by multi-parametric MRI: implications for aging-associated neuroinflammation.

Lipopolysaccharide (LPS)-induced encephalopathy induces neuroinflammation. Long-term neuroinflammation is associated with aging and subsequent cognitive impairment (CI). We treated rats that had LPS-induced neuroinflammation with OKN-007, with an anti-inflammatory agent currently considered an anti-cancer investigational new drug in clinical trials for glioblastoma (GBM). Contrast-enhanced magnetic resonance imaging (MRI) (CE-MRI), perfusion MRI, and MR spectroscopy were used as methods to assess long-term (up to 6 weeks post-LPS) alterations in blood-brain barrier (BBB) permeability, microvascularity, and metabolism, respectively, and the therapeutic effect of OKN-007. A free radical-targeted molecular MRI approach was also used to detect the effect of OKN-007 on brain free radical levels at 24 h and 1 week post-LPS injection. OKN-007 was able to reduce BBB permeability in the cerebral cortex and hippocampus at 1 week post-LPS using CE-MRI. OKN-007 was able to restore vascular perfusion rates by reducing LPS-induced increased relative cerebral blood flow (rCBF) in the cortex and hippocampus regions at all time points studied (1, 3, and 6 weeks post-LPS). OKN-007 was also able to restore LPS-induced brain metabolite depletions. NAA/Cho, Cr/Cho, and Myo-Ins/Cho metabolite ratios at 1, 3, and 6 weeks post-LPS were all restored to normal levels following OKN-007 treatment. OKN-007 also reduced LPS-induced free radical levels at 24 h and 1 week post-LPS, as detected by free radical-targeted MRI. LPS-exposed rats were compared with saline-treated controls and LPS + OKN-007-treated animals. We clearly demonstrated that OKN-007 restores LPS-induced BBB dysfunction, impaired vascularity, and decreased brain metabolites, all long-term neuroinflammatory indicators, as well as decreases free radicals in a LPS-induced neuroinflammation model. OKN-007 should be considered an anti-inflammatory agent for age-associated neuroinflammation.

The clinical impact of bedside fiberoptic laryngoscopic recording on a tertiary consult service.

OBJECTIVES/HYPOTHESIS: Fiberoptic laryngoscopy is dependent on accurate descriptions of examination findings. Traditional recording methods can be impractical for inpatient consults. Therefore, we aim to determine the utility of a smartphone-coupled portable recording system with flexible laryngoscopy for transmitting information between resident and attending physicians in a real-time setting. STUDY DESIGN: Pilot prospective study in a tertiary academic hospital. METHODS: This is a prospective study of inpatient consultations in a tertiary referral hospital over a 3-month period from April 2015 to June 2015. Flexible laryngoscopy was performed by a resident physician, and mobile recordings were relayed to an attending physician. Concordance of laryngoscopy interpretations between resident and attending physicians as well as changes in management were documented. RESULTS: Seventy-nine fiberoptic examinations were recorded and compared. Each consult was categorized as follows: airway evaluation (AE) (43%, 34/79), voice evaluation (VE) (3.7%, 3/79), dysphagia (D) (24%, 19/79), and aerodigestive tract mass/pathology (ADM) (29.1%, 23/79). Nine examinations showed discordance between resident and attending interpretations. Inter-rater agreement was good, with a kappa value of 0.747 (95% confidence interval: 0.643-0.851). The frequency of discordant exams within each group was as follows: AE (15%, 5/34), VE (33%, 1/3), D (11%, 2/19), and ADM (4.3%, 1/23). In five patients, changes in laryngoscopy interpretation changed clinical management. Seven nondiscordant exams had a change in management after attending review. Of the 79 exams, only one required repeat flexible laryngoscopy by the attending physician. CONCLUSIONS: Portable recording of flexible laryngoscopy is an effective tool for timely management of inpatient consultations. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:818-822, 2018.

Comparison of Performance of Improved Serum Estimators of Glomerular Filtration Rate (GFR) to 99mTc-DTPA GFR Methods in Patients with Hepatic Cirrhosis.

Glomerular filtration rate (GFR) measurements are critical in patients with hepatic cirrhosis but potentially erroneous when based on serum creatinine. New equations for estimated GFR (eGFR) have shown variable performance in cirrhotics, possibly because of inaccuracies in reference methods for measured GFR (mGFR). The primary objective was to compare the performance of 4 improved eGFR equations with a 1-compartment, 2-sample plasma slope intercept 99mTc-DTPA mGFR method to determine whether any of the eGFR calculations could replace plasma 99mTc-DTPA mGFR in patients with cirrhosis. The secondary objective was to test the hypothesis that mGFR using voluntary voided urine collections introduces error compared with plasma-only methods. Methods: Fifty-four patients with hepatic cirrhosis underwent mGFR determinations from 2 plasma samples at 1 and 3 h after intravenous administration of 185 MBq of 99mTc-DTPA. GFR was also generated by a UV/P calculation derived from blood and urine samples. These mGFRs were compared with the eGFRs generated by 4 estimating equations: MDRD (Modified Diet in Renal Disease), CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) (serum creatinine [SCr]), CKD-EPI (cystatin [CysC]), and CKD-EPI (CysC+SCr). eGFRs were compared with mGFRs by Pearson correlation, precision, bias, percentage bias, and accuracy (eGFRs varying by <10% [p10], <20% [p20] or <30% [p30] from the corresponding mGFR). Results: All eGFRs showed poorer performance when the UV/P 99mTc-DTPA mGFR was used as the reference than when the plasma 99mTc-DTPA mGFR was used. When compared with the plasma 99mTc-DTPA mGFR method, the performance of all eGFR equations was superior to most published reports. There was a moderately good positive correlation between eGFRs and mGFRs. When compared with plasma 99mTc-DTPA mGFR, precision of eGFRs was in the range of 14-20 mL/min and showed a negligible bias. Compared with the plasma 99mTc-DTPA mGFR, CKD-EPI (CysC+SCr) showed the best overall performance and accuracy, at 85.19% (p30), 75.93% (p20), and 42.59% (p10). Conclusion: Estimating equations for measuring eGFR performed better than in most published reports, attributable to use of the plasma 99mTc-DTPA mGFR method as a reference. CKD-EPI (CysC+SCr) eGFR showed the best overall performance. However, more discriminating methods may be required when accurate GFR measurements are necessary. mGFR measurements using urine collections may introduce error compared with plasma-only methods.

FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.

BACKGROUND: Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. METHODS: Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using (18) F-fluorodeoxyglucose (FDG) and (18) F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment. RESULTS: Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy. CONCLUSIONS: While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed metabolic response beginning after two weeks in metastatic renal cell carcinoma treated with a continuous daily dose of 37.5 mg sunitinib. The results provide evidence of tumor response to lower-dose sunitinib while also supporting the inclusion of PET imaging as a tool for early assessment in oncological clinical trials. TRIAL REGISTRATION: ID: NCT00694096.

Histamine Receptor 1 and 2 Antagonists Alter Biodistribution of Radioiodine.

UNLABELLED: Nuclear medicine technology assumes responsibility for examination-specific patient preparation procedures. This requires a clear understanding of the possible effects of medications on the outcome of examinations. There is evidence that common over-the-counter drugs, histamine 1 (H1) and histamine 2 (H2) receptor blockers and proton pump inhibitors, may directly or indirectly affect thyroid function. The objective was to determine whether short-term use of these drugs alters biodistribution of radioiodine in a rat model. METHODS: Rats received no drug (controls) or daily subcutaneous injections of H1 blocker (promethazine), H2 blocker (famotidine), or proton pump inhibitor (esomeprazole) commencing 1 d before a single intraperitoneal injection of 0.037 MBq (1 µCi) of (131)I (NaI) and continuing daily until euthanasia at either 1 d or 8 d after (131)I. Organ uptake of (131)I by control and drug-treated rats was compared by γ-well counting. RESULTS: Promethazine significantly increased uptake of (131)I by the thyroid (drug-treated-to-control ratios) both at 1 d (1.32) and 8 d (1.52) after (131)I. Both famotidine and promethazine (respectively) significantly increased salivary gland uptake of (131)I (drug-treated-to-control ratios) at 1 d (1.37, 1.40) and 8 d (4.52, 5.57) after (131)I. Promethazine significantly increased gastric (131)I uptake (drug-treated-to-control ratios) at 1 d (1.47) and 8 d (1.46) after (131)I. Famotidine and promethazine (respectively) significantly decreased uptake of (131)I by the liver (drug-treated-to-control ratios) at 1 d (0.60, 0.71) after (131)I but resulted in a marked increase over control levels (11.21, 9.28) at 8 d. Blood levels of (131)I were not altered by drug treatment. Esomeprazole did not affect radioiodine distribution. CONCLUSION: H1 and H2 blockers alter the biodistribution of radioiodine in the rat. Although the findings remain to be confirmed in humans, these drugs could increase radiation exposure to nontarget tissues, particularly the stomach and salivary tissue, during (131)I therapy and consideration should be given toward avoiding the elective use of these drugs during radioiodine therapy.

NF-κB and stat3 transcription factor signatures differentiate HPV-positive and HPV-negative head and neck squamous cell carcinoma.

Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head and neck squamous cell carcinoma (HNSCC) subgroups by inferential analysis of target gene expression, correcting for the effects of DNA methylation and copy number. Using this discovery pipeline, we determined that human papillomavirus-related (HPV+) and HPV- HNSCC differed significantly based on the activity levels of key TFs including AP1, STATs, NF-κB and p53. Immunohistochemical analysis confirmed that HPV- HNSCC is characterized by co-activated STAT3 and NF-κB pathways and functional studies demonstrate that this phenotype can be effectively targeted with combined anti-NF-κB and anti-STAT therapies. These discoveries correlate strongly with previous findings connecting STATs, NF-κB and AP1 in HNSCC. We identified five top-scoring pair biomarkers from STATs, NF-κB and AP1 pathways that distinguish HPV+ from HPV- HNSCC based on TF activity and validated these biomarkers on TCGA and on independent validation cohorts. We conclude that a novel approach to TF pathway analysis can provide insight into therapeutic targeting of patient subgroup for heterogeneous disease such as HNSCC.