Essentials of Theranostics: A Guide for Physicians and Medical Physicists.

Radiopharmaceutical therapies (RPTs) are gaining increased interest with the recent emergence of novel safe and effective theranostic agents, improving outcomes for thousands of patients. The term theranostics refers to the use of diagnostic and therapeutic agents that share the same molecular target; a major step toward precision medicine, especially for oncologic applications. The authors dissect the fundamentals of theranostics in nuclear medicine. First, they explain the radioactive decay schemes and the characteristics of emitted electromagnetic radiation used for imaging, as well as particles used for therapeutic purposes, followed by the interaction of the different types of radiation with tissue. These concepts directly apply to clinical RPTs and play a major role in the efficacy and toxicity profile of different radiopharmaceutical agents. Personalized dosimetry is a powerful tool that can help estimate patient-specific absorbed doses, in tumors as well as normal organs. Dosimetry in RPT is an area of active investigation, as most of what we know about the relationship between delivered dose and tissue damage is extrapolated from external-beam radiation therapy; more research is needed to understand this relationship as it pertains to RPTs. Tumor heterogeneity is increasingly recognized as an important prognostic factor. Novel molecular imaging agents, often in combination with fluorine 18-fluorodeoxyglucose, are crucial for assessment of target expression in the tumor and potential hypermetabolic disease that may lack the molecular target expression. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Imaging Biomarkers and Liquid Biopsy in Assessment of Cervical Cancer.

ABSTRACT: The role of imaging has been increasing in pretherapy planning and response assessment in cervical cancer, particularly in high-resource settings that provide access to computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). In 2018, imaging was incorporated into the International Federation of Gynecology and Obstetrics staging system for cervical cancer. Magnetic resonance imaging is advantageous over CT for evaluation of the primary cervical cancer size and extent, because of superior contrast resolution. Furthermore, quantitative methods, including diffusion-weighted and dynamic contrast-enhanced MRI, show promise in improving treatment response and prognosis evaluation. Molecular imaging with fluorodeoxyglucose-PET/CT and PET/MRI can be particularly helpful in the detection of nodal disease and distant metastases. Semiautomated delineation of 3-dimensional tumor regions of interest has facilitated the development of novel PET-derived biomarkers that include metabolic volume and radiomics textural analysis features for prediction of outcomes. However, posttreatment inflammatory changes can be a confounder and lymph node evaluation is challenging, even with the use of PET/CT. Liquid biopsy has emerged as a promising tool that may be able to overcome some of the drawbacks inherent with imaging, such as limited ability to detect microscopic metastases or to distinguish between postchemoradiotherapy changes and residual tumor. Preliminary evidence suggests that liquid biopsy may be able to identify cervical cancer treatment response and resistance earlier than traditional methods. Future work should prioritize how to best synergize imaging and liquid biopsy as an integrated approach for optimal cervical cancer management.

18F-FES PET/CT Improves the Detection of Intraorbital Metastases in Estrogen-Receptor-Positive Breast Cancer: Two Representative Cases and Review of the Literature.

Orbital metastases are a rare but life-altering complication in cancer. Most commonly seen in breast cancer, metastases to the optic nerves or extraocular muscles can have a devastating impact on visual acuity and quality of life. Hormone receptor status plays a central role in metastatic breast cancer treatment, with endocrine therapy often representing first-line therapy in hormone-receptor-positive cancers. Staging and treatment response evaluation with positron emission tomography (PET) computed tomography (CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) is limited by high physiologic uptake in the intracranial and intraorbital compartments. Thus, traditional staging scans with 18F-FDG PET/CT may under-detect intraorbital and intracranial metastatic disease and inaccurately evaluate active metastatic disease burden. In comparison, 18F-fluoroestradiol (18F-FES) is a novel estrogen-receptor-specific PET radiotracer, which more accurately assesses the intracranial and intraorbital compartments in patients with estrogen-receptor-positive (ER+) cancers than 18F-FDG, due to lack of physiologic background activity in these regions. We present two cases of breast cancer patients with orbital metastases confirmed on MR imaging who underwent PET/CT imaging with 18F-FES and 18F-FDG. Multimodality imaging with 18F-FES PET/CT offers higher detection sensitivity of orbital metastases, compared with traditional 18F-FDG PET/CT imaging, and can improve the assessment of treatment response in patients with estrogen-receptor-positive (ER+) cancers.

Improved Prognosis of Treatment Failure in Cervical Cancer with Nontumor PET/CT Radiomics.

Radiomics has been applied to predict recurrence in several disease sites, but current approaches are typically restricted to analyzing tumor features, neglecting nontumor information in the rest of the body. The purpose of this work was to develop and validate a model incorporating nontumor radiomics, including whole-body features, to predict treatment outcomes in patients with previously untreated locoregionally advanced cervical cancer. Methods: We analyzed 127 cervical cancer patients treated definitively with chemoradiotherapy and intracavitary brachytherapy. All patients underwent pretreatment whole-body 18F-FDG PET/CT. To quantify effects due to the tumor itself, the gross tumor volume (GTV) was directly contoured on the PET/CT image. Meanwhile, to quantify effects arising from the rest of the body, the planning target volume (PTV) was deformably registered from each planning CT to the PET/CT scan, and a semiautomated approach combining seed-growing and manual contour review generated whole-body muscle, bone, and fat segmentations on each PET/CT image. A total of 965 radiomic features were extracted for GTV, PTV, muscle, bone, and fat. Ninety-five patients were used to train a Cox model of disease recurrence including both radiomic and clinical features (age, stage, tumor grade, histology, and baseline complete blood cell counts), using bagging and split-sample-validation for feature reduction and model selection. To further avoid overfitting, the resulting models were tested for generalization on the remaining 32 patients, by calculating a risk score based on Cox regression and evaluating the c-index (c-index > 0.5 indicates predictive power). Results: Optimal performance was seen in a Cox model including 1 clinical biomarker (whether or not a tumor was stage III-IVA), 2 GTV radiomic biomarkers (PET gray-level size-zone matrix small area low gray level emphasis and zone entropy), 1 PTV radiomic biomarker (major axis length), and 1 whole-body radiomic biomarker (CT bone root mean square). In particular, stratification into high- and low-risk groups, based on the linear risk score from this Cox model, resulted in a hazard ratio of 0.019 (95% CI, 0.004, 0.082), an improvement over stratification based on clinical stage alone, which had a hazard ratio of 0.36 (95% CI, 0.16, 0.83). Conclusion: Incorporating nontumor radiomic biomarkers can improve the performance of prognostic models compared with using only clinical and tumor radiomic biomarkers. Future work should look to further test these models in larger, multiinstitutional cohorts.

Gated single-photon emission computed tomography myocardial perfusion imaging phase analysis as an imaging biomarker for mortality prediction in heart failure patients undergoing cardiac resynchronization therapy.

OBJECTIVE: Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in heart failure patients. The purpose of this study was to assess the value of gated myocardial perfusion single-photon emission computed tomography (GMPS) phase analysis for predicting survival in heart failure patients undergoing CRT. METHODS: This retrospective cohort study evaluated heart failure patients who underwent GMPS prior to CRT. Phase histogram bandwidth (PHB) and phase SD (PSD) were calculated using GMPS data. Cox proportional hazards model was used to identify independent predictors of overall survival (OS). RESULTS: A total of 35 patients (age 65.1 ± 13.3, 27 men and 8 women), who were followed for mean of 4.1 ± 2.9 years, were enrolled in the study. PSD of greater than 45° was found to be an independent predictor of poor OS (hazard ratio = 12.63, P = 0.011) when compared with age (hazard ratio = 1.00, P = 0.922), gender (hazard ratio = 0.31, P = 0.155), NYHA class (hazard ratio = 0.45, P = 0.087), QRS duration greater than 150 ms (hazard ratio = 2.38, P = 0.401), pre-CRT left ventricular ejection fraction (LVEF) (hazard ratio = 0.95, P = 0.175) and etiology of heart failure (hazard ratio = 1.42, P = 0.641). Furthermore, PHB greater than 140° was also found to be an independent predictor of poor OS (hazard ratio = 5.63, P = 0.040) when compared with age, gender, NYHA class, QRS duration greater than 150 ms, pre-CRT LVEF and etiology of heart failure. CONCLUSIONS: PSD and PHB, measured by GMPS, may serve as biomarkers for the prediction of survival in patients undergoing CRT.

Assessment of Motor Dysfunction with Virtual Reality in Patients Undergoing [123I]FP-CIT SPECT/CT Brain Imaging.

[123I]FP-CIT SPECT has been valuable for distinguishing Parkinson disease (PD) from essential tremor. However, its performance for quantitative assessment of motor dysfunction has not been established. A virtual reality (VR) application was developed and compared with [123I]FP-CIT SPECT/CT for detection of severity of motor dysfunction. Forty-four patients (21 males, 23 females, age 64.5 ± 12.4) with abnormal [123I]FP-CIT SPECT/CT underwent assessment of bradykinesia, activities of daily living, and tremor with VR. Support vector machines (SVM) machine learning models were applied to VR and SPECT data. Receiver operating characteristic (ROC) analysis demonstrated greater area under the curve (AUC) for VR (0.8418, 95% CI 0.6071-0.9617) compared with brain SPECT (0.5357, 95% CI 0.3373-0.7357, p = 0.029) for detection of motor dysfunction. Logistic regression identified VR as an independent predictor of motor dysfunction (Odds Ratio 326.4, SE 2.17, p = 0.008). SVM for prediction of the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) demonstrated greater R-squared of 0.713 (p = 0.008) for VR, compared with 0.0764 (p = 0.361) for brain SPECT. This study demonstrates that VR can be safely used in patients prior to [123I]FP-CIT SPECT imaging and may improve prediction of motor dysfunction. This test has the potential to provide a simple, objective, quantitative analysis of motor symptoms in PD patients.

The prognostic and diagnostic value of 18F-FDG PET/CT for assessment of symptomatic osteoarthritis.

OBJECTIVE: The objective of this study was to assess the clinical significance of increased fluorine-18-fluorodeoxyglucose (F-FDG) uptake on PET/CT in joints for evaluation of symptomatic osteoarthritis (OA) and prediction of progression. PATIENTS AND METHODS: In this prospective study, shoulder, hip, and knee joints were imaged in 65 patients undergoing routine F-FDG PET/CT imaging. Patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire to assess joint pain, stiffness, and physical function. Standardized uptake values (SUVs) were measured in hip, knee, acromioclavicular (AC), and glenohumeral (GH) joints. Scout PET/CT images were evaluated for OA using the Kellgren and Lawrence (K/L) system. Patients were followed-up for 5 years to determine the progression of OA on the basis of follow-up imaging or surgical intervention. RESULTS: SUV of knee (r=0.309, P=0.0003), hip (r=0.260, P=0.0027), AC (r=0.186, P=0.0313), and GH (r=0.191, P=0.0271) joints correlated with WOMAC overall scores. Furthermore, SUV of knee (r=0.410, P<0.0001), hip (r=0.203, P=0.0199), and AC (r=0.364, P<0.0001) joints correlated with K/L scores. The area under the receiver operating characteristic curves for SUV were 0.734 (knee), 0.678 (hip), 0.661 (AC), and 0.544 (GH) for symptomatic OA detection based on WOMAC overall z-score greater or equal to 2. Compared with K/L score [hazard ratio (HR)=0.798, P=0.5324], age (HR=0.992, P=0.8978), and WOMAC overall score (HR=1.089, P=0.1265), only SUV (HR=5.653, P=0.0229) was an independent predictor of OA progression in the knees. CONCLUSION: F-FDG PET/CT may be helpful with localization of painful abnormalities in the inflamed regions of the joints, which could potentially be used to direct individualized treatment in moderate and severe OA. Furthermore, SUV measurement on F-FDG PET/CT could serve as an inflammation activity index in the knees that may be predictive of outcomes and progression rate of OA.

Evaluation of Virtual Reality for Detection of Lung Nodules on Computed Tomography.

Virtual reality (VR) systems can offer benefits of improved ergonomics, but their resolution may currently be limited for the detection of small features. For detection of lung nodules, we compared the performance of VR versus standard picture archiving and communication system (PACS) monitor. Four radiologists and 1 novice radiologist reviewed axial computed tomography (CTs) of the thorax using standard PACS monitors (SM) and a VR system (HTC Vive, HTC). In this study, 3 radiologists evaluated axial lung-window CT images of a Lungman phantom. One radiologist and the novice radiologist reviewed axial lung-window patient CT thoracic images (32 patients). This HIPAA-compliant study was approved by the institutional review board. Detection of 227 lung nodules on patient CTs did not result in different sensitivity with SM compared with VR. Detection of 23 simulated Lungman phantom lung nodules on CT with SM resulted in statistically greater sensitivity (78.3%) than with VR (52.2%, P = .041) for 1 of 3 radiologists. The trend was similar but not significant for the other radiologists. There was no significant difference in the time spent by readers reviewing CT images with VR versus SM. These findings indicate that performance of a commercially available VR system for detection of lung nodules may be similar to traditional radiology monitors for assessment of small lung nodules on CTs of the thorax for most radiologists. These results, along with the potential of improving ergonomics for radiologists, are promising for the future development of VR in diagnostic radiology.

Comparison of lesion-to-cerebellum uptake ratios and standardized uptake values in the evaluation of lung nodules with 18F-FDG PET.

OBJECTIVE: To evaluate the clinical performance of the lesion-to-cerebellum uptake ratio (LCR), a semiquantitative index for differentiating malignant from benign lung nodules with [F]fluorodeoxyglucose positron emission tomography (F-FDG PET). METHODS: Thirty-six patients (16 females, 20 males; median age, 73 years; range, 41-87 years) with 42 known or suspected malignant lung nodules underwent whole-body PET imaging after an intravenous injection of a mean dose of 543+/-69 MBq (14.7+/-1.9 mCi) of F-FDG. The standardized uptake value (SUV) and the LCR were calculated for each nodule and receiver operating characteristic (ROC) curves were analysed using the ROCKIT 0.9B software package. RESULTS: Surgical pathology and follow-up with serial computed tomography scans for at least 24 months revealed 18 malignant lung lesions and 24 benign lesions less than 3.0 cm in size. The mean LCR was 0.70+/-0.40 for malignant nodules and 0.23+/-0.12 for benign nodules (P<0.001, two-tailed test). The area under the estimated ROC curve was 0.8660 for SUV data and 0.9197 for LCR data (P=0.2408, two-tailed test). CONCLUSIONS: The LCR method appears to be a valuable semiquantitative index for the evaluation of malignancy in pulmonary nodules with F-FDG PET, which is simple to perform clinically and does not require accurate measurements of body weight or the residual activity in the syringe utilized for F-FDG injection.

Prognostic value of post-Yttrium 90 radioembolization therapy 18F-fluorodeoxyglucose positron emission tomography in patients with liver tumors.

OBJECTIVE: This study assessed the benefit of post-therapy 18F-FDG PET/CT versus CT alone in identifying malignant liver tumor progression following radioembolization with Y-90 microspheres. METHODS: 24 patients with 44 liver tumors underwent CT imaging pre-radioembolization and PET/CT post-radioembolization. Predictive value of Response Evaluation Criteria in Solid Tumors (RECIST 1.1), The World Health Organization (WHO), mRECIST and European Association for the Study of the Liver (EASL) with PET/CT versus CT alone was assessed. RESULTS: Prediction of liver malignancy progression was improved (p<0.05) for tumors labeled as non-responding based on combined PET/CT with RECIST 1.1, WHO, mRECIST, and EASL criteria compared to assessment without PET. CONCLUSIONS: The addition of post-therapy PET to routine CT in patients with hepatic tumors undergoing radioembolization may improve identification of non-responding tumors.

Whole-body radiation dosimetry of 2-[18F]Fluoro-A-85380 in human PET imaging studies.

2-[18F]Fluoro-A-85380 (2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine, 2-[18F]FA) is a recently developed PET radioligand for noninvasive imaging of nicotinic acetylcholine receptors. Previous radiation absorbed dose estimates for 2-[18F]FA were limited to evaluation of activity in only several critical organs. Here, we performed 2-[18F]FA radiation dosimetry studies on two healthy human volunteers to obtain data for all important body organs. Intravenous injection of 2.9 MBq/kg of 2-[18F]FA was followed by dynamic PET imaging. Regions of interest were placed over images of each organ to generate time-activity curves, from which we computed residence times. Radiation absorbed doses were calculated from the residence times using the MIRDOSE 3.0 program (version 3.0, ORISE, Oak Ridge, TN). The urinary bladder wall receives the highest radiation absorbed dose (0.153 mGy/MBq, 0.566 rad/mCi, for a 2.4-h voiding interval), followed by the liver (0.0496 mGy/MBq, 0.184 rad/mCi) and the kidneys (0.0470 mGy/MBq, 0.174 rad/mCi). The mean effective dose equivalent is estimated to be 0.0278 mSv/MBq (0.103 rem/mCi), indicating that radiation dosimetry associated with 2-[18F]FA is within acceptable limits.

Evaluation of metastatic meningioma with 2-deoxy-2-[18F]fluoro-D-glucose PET/CT.

PURPOSE: The purpose of this study was to characterize the 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET/CT imaging findings of sacral metastatic meningioma. MATERIALS AND METHODS: An 18-year-old woman with a history of metastatic meningioma, who presented with intractable pain and spasm of the right lower extremity, underwent FDG PET/CT imaging. RESULTS: FDG PET/CT scan demonstrated a moderately hypermetabolic sacral mass. The biopsy of the lesion was consistent with a high-grade malignant meningioma. CONCLUSIONS: Although meningioma is typically a benign tumor, in rare instances, it metastasizes. The current case example exhibits moderately increased metabolism despite findings of high-grade malignancy on biopsy.

The role of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography in monitoring the immunosuppressive therapy response of inflammatory myofibroblastic tumor.

PURPOSE: To compare the pre and post treatment 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging findings of an inflammatory myofibroblastic tumor (IMT) with its clinical response to immunosuppressive therapy. PROCEDURE: Forty-nine-year-old female presented with dyspnea, chest pain, and weight loss and underwent an FDG-PET/CT scan before and after mediastinal biopsy and treatment with dexamethasone and thalidomide. RESULTS: FDG-PET/CT scan demonstrated a hypermetabolic mediastinal mass. The biopsy of the lesion was consistent with IMT. Following immunosuppressive therapy, the patient's clinical findings resolved, and PET/CT showed a significant decrease in the FDG uptake and the size of the mass. CONCLUSION: Pre-treatment imaging features and post-treatment imaging characteristics of IMT correlate with clinical findings and suggest that FDG-PET/CT may be useful as an adjunct to clinical evaluation in monitoring of immunosuppressive therapy of IMT.

Comparison between 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and positron emission tomography/computed tomography hardware fusion for staging of patients with lymphoma.

PURPOSE: 2-Deoxy-2-[18F]fluoro-D-Glucose positron emission tomography (FDG-PET) stages patients with Hodgkin's disease (HD) and Non-Hodgkin's lymphoma (NHL) with higher accuracy than computed tomography (CT). We sought to determine whether integrated (hardware) fused PET/CT imaging results in further improvements in staging accuracy. PROCEDURES: Seventy-three patients (age 51 +/- 17 years, 37 female, 36 male) with HD (n = 20) or NHL (n = 53) undergoing staging were studied with an integrated PET/CT system. Image findings were verified by clinical follow up, additional imaging and when available, histology. RESULTS: Thirty-four of 73 patients (46.5%) had evidence of disease and 39 were disease free as confirmed by clinical evaluation and follow-up for 41 +/- 22 weeks (n = 73), including biopsy (n = 26), and other imaging modalities (n = 52) when available. A discordant image interpretation between PET and PET/CT occurred in seven patients (10%). PET/CT correctly upstaged two and downstaged five patients. Overall staging was accurate in 93% with PET/CT and 84% with PET (P = 0.03). CONCLUSION: Lymphoma is staged with higher accuracy using PET/CT than PET alone.

Standard chest radiograph predicts left ventricular lead location in chronic resynchronization therapy patients more accurately than intraoperative fluoroscopy.

INTRODUCTION: Targeting the proper left ventricular lead site is important in cardiac resynchronization therapy (CRT) procedures, as suboptimal lead locations may result in a lack of clinical response. Left ventricular lead locations are typically confirmed using fluoroscopy (fluoro) with AP, RAO, and LAO orientations. However, standard fluoro may inadequately delineate true left ventricular lead locations, due to insufficient angulation or extreme cardiac rotation. Posteroanterior and lateral chest radiograph (CXRPAL), performed routinely to verify lead stability and freedom from complication, may better confirm left ventricular lead location due to utilization of a straight lateral view. HYPOTHESIS: Compared to fluoro, lead localization using CXRPAL will be more predictive of true left ventricular lead location in CRT patients. METHODS: Of 252 medically optimized CHF patients who underwent CRT implantation by multiple operators from October 2001 to August 2011, 46 (mean age, 58.9 ± 13.2 years; 10 female; 19 ICM; 19 LBBB; mean ejection fraction, 26.6 ± 8.9 %; mean QRS width, 144.4 ms) had CT scanning performed as part of routine medical care and comprise this study. Operative reports of left ventricular lead location by fluoro were reviewed. Left ventricular lead location was identified on CXRPAL by three independent observers blinded to operative results. Left ventricular lead locations according to fluoro and CXRPAL were correlated with CT scan at a mean follow-up of 57.6 ± 28.8 months (Tables 1 and 2). RESULTS: Compared to standard fluoro, CXRPAL agreed better with CT scan (κ = 0.413 fluoro vs. κ = 0.864 CXRPAL on the vertical axis, and κ = 0.086 fluoro vs. κ = 0.864 CXRPAL on the horizontal axis) for identification of left ventricular lead location. CONCLUSIONS: In this small study of 46 CRT patients, interpretation of left ventricular lead location using CXRPAL correlated better with true lead location identified on CT scan, compared to standard fluoroscopy. Use of a steep lateral view during CRT implantation may be necessary to accurately identify left ventricular lead locations.

Imaging and modeling of myocardial metabolism.

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed.

Utility of fluorodeoxyglucose-positron emission tomography in the identification of new lesions in lung cancer patients for the assessment of therapy response.

PURPOSE: Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) has added positron emission tomography (PET) as an optional complement for the detection of new lesions. In this study, we evaluate the utility of fluorodeoxyglucose (FDG)-PET in the identification of new lesions and progressive disease not recognized on computed tomography (CT) in patients with nonsmall cell lung cancer (NSCLC) undergoing therapy. MATERIALS AND METHODS: Seventy patients (30 female, 40 male; mean age 67±14 years, range, 39-94 years) with NSCLC underwent FDG-PET before and after chemotherapy and/or radiotherapy, whereas 69 patients underwent CT imaging. Overall (OS) and progression-free survivals (PFS) were calculated for RECIST 1.1 with CT alone, RECIST 1.1 with PET for the identification of new lesions, visual PET, and semiquantitative PET using a change in standardized uptake value ranging from -15 to -50%. RESULTS: PET identified new lesions in 26 patients, resulting in 10 patients (14.5%) being upgraded to progressive disease. The combination of CT and PET for the detection of new lesions improved the prediction of survival (OS: P=0.0491 for all stages and P=0.0033 for stage IV; PFS: P=0.0045 for stage IV) compared with CT imaging alone (OS: P=0.1362 for all stages and P=0.1625 for stage IV; PFS: P=0.0632 for stage IV). Furthermore, a change in standardized uptake value of -35% was the most discriminative for the prediction of survival for the semiquantitative PET approach (OS: P=0.0393 for all stages, P=0.0051 for stage IV; PFS: P=0.0092 for stage IV) and more discriminative than the visual PET approach (OS: P=0.2699 for all stages, P=0.0105 for stage IV; PFS: P=0.014 for stage IV). CONCLUSION: FDG-PET is helpful in identifying new lesions in NSCLC patients, resulting in the improved assessment of therapy response with CT imaging combined with FDG-PET compared with CT imaging alone. Although RECIST 1.1 includes FDG-PET only as an optional adjunct, we recommend the implementation of PET imaging in the assessment of therapy response.

Assessment of metabolic phenotypes in patients with non-ischemic dilated cardiomyopathy undergoing cardiac resynchronization therapy.

Studies of myocardial metabolism have reported that contractile performance at a given myocardial oxygen consumption (MVO2) can be lower when the heart is oxidizing fatty acids rather than glucose or lactate. The objective of this study is to assess the prognostic value of myocardial metabolic phenotypes in identifying non-responders among non-ischemic dilated cardiomyopathy (NIDCM) patients undergoing cardiac resynchronization therapy (CRT). Arterial and coronary sinus plasma concentrations of oxygen, glucose, lactate, pyruvate, free fatty acids (FFA), and 22 amino acids were obtained from 19 male and 2 female patients (mean age 56 ± 16) with NIDCM undergoing CRT. Metabolite fluxes/MVO2 and extraction fractions were calculated. Flux balance analysis (FBA) was performed with MetaFluxNet 1.8 on a metabolic network of the cardiac mitochondria (189 reactions, 230 metabolites) reconstructed from mitochondrial proteomic data (615 proteins) from human heart tissue. Non-responders based on left ventricular ejection fraction (LVEF) demonstrated a greater mean FFA extraction fraction (35% ± 17%) than responders [18 ± 10%, p = 0.0098, area under the estimated ROC curve (AUC) was 0.8238, S.E. 0.1115]. Calculated adenosine triphosphate (ATP)/MVO2 using FBA correlated with change in New York Heart Association (NYHA) class (rho = 0.63, p = 0.0298; AUC = 0.8381, S.E. 0.1316). Non-responders based on both LVEF and NYHA demonstrated a greater mean FFA uptake/MVO2 (0.115 ± 0.112) than responders (0.034 ± 0.030, p = 0.0171; AUC = 0.8593, S.E. 0.0965). Myocardial FFA flux and calculated maximal ATP synthesis flux using FBA may be helpful as biomarkers in identifying non-responders among NIDCM patients undergoing CRT.

Incidental finding of metastatic papillary thyroid carcinoma in a patient with primary hyperparathyroidism.

OBJECTIVE: To report on the management of a patient with the rare concurrence of primary hyperparathyroidism and incidentally found metastatic papillary thyroid carcinoma in an adjacent lymph node. METHODS: We present a case report, including scintigraphic and histologic documentation, and a summary of the related literature. RESULTS: Primary hyperparathyroidism with concomitant occurrence of nonmedullary thyroid carcinoma is rare, occurring in less than 4% of patients. We report a case of a 53-year-old woman with no prior history of endocrine disease with primary hyperparathyroidism and an incidental finding of a concurrent thyroid carcinoma. In this patient, technetium 99m scintigraphy revealed a parathyroid adenoma beneath the inferior pole of the left thyroid bed. Parathyroidectomy was performed successfully with no complications. The final pathology examination showed a large parathyroid adenoma with an incidental finding of a small adjacent lymph node containing metastatic papillary thyroid carcinoma. The patient subsequently underwent total thyroidectomy, and the pathology evaluation revealed papillary thyroid carcinoma, follicular variant. CONCLUSION: To our knowledge, this case of concomitant primary hyperparathyroidism and papillary thyroid cancer is unique in the way in which the diagnosis of metastatic papillary thyroid cancer was made. The presence of parathyroid adenoma should not exclude the diagnosis of thyroid carcinoma; therefore, careful thyroid evaluation should be considered for all patients with primary hyperparathyroidism.