Search

Oncological diseases account for a significant portion of the burden on public healthcare systems with associated costs driven primarily by complex and long-lasting therapies. Through the visualization of patient-specific morphology and functional-molecular pathways, cancerous tissue can be detected and characterized non-invasively, so as to provide referring oncologists with essential information to support therapy management decisions. Following the onset of stand-alone anatomical and functional imaging, we witness a push towards integrating molecular image information through various methods, including anato-metabolic imaging (e.g., PET/CT), advanced MRI, optical or ultrasound imaging.This perspective paper highlights a number of key technological and methodological advances in imaging instrumentation related to anatomical, functional, molecular medicine and hybrid imaging, that is understood as the hardware-based combination of complementary anatomical and molecular imaging. These include novel detector technologies for ionizing radiation used in CT and nuclear medicine imaging, and novel system developments in MRI and optical as well as opto-acoustic imaging. We will also highlight new data processing methods for improved non-invasive tissue characterization. Following a general introduction to the role of imaging in oncology patient management we introduce imaging methods with well-defined clinical applications and potential for clinical translation. For each modality, we report first on the status quo and, then point to perceived technological and methodological advances in a subsequent status go section. Considering the breadth and dynamics of these developments, this perspective ends with a critical reflection on where the authors, with the majority of them being imaging experts with a background in physics and engineering, believe imaging methods will be in a few years from now.Overall, methodological and technological medical imaging advances are geared towards increased image contrast, the derivation of reproducible quantitative parameters, an increase in volume sensitivity and a reduction in overall examination time. To ensure full translation to the clinic, this progress in technologies and instrumentation is complemented by advances in relevant acquisition and image-processing protocols and improved data analysis. To this end, we should accept diagnostic images as "data", and - through the wider adoption of advanced analysis, including machine learning approaches and a "big data" concept - move to the next stage of non-invasive tumour phenotyping. The scans we will be reading in 10 years from now will likely be composed of highly diverse multi-dimensional data from multiple sources, which mandate the use of advanced and interactive visualization and analysis platforms powered by Artificial Intelligence (AI) for real-time data handling by cross-specialty clinical experts with a domain knowledge that will need to go beyond that of plain imaging.

PET/CT radiotracer infiltration is not uncommon and is often outside the imaging field of view. Infiltration can negatively affect image quality, image quantification, and patient management. Until recently, there has not been a simple way to routinely practice PET radiopharmaceutical administration quality control and quality assurance. Our objectives were to quantify infiltration rates, determine associative factors for infiltration, and assess whether rates could be reduced at multiple centers and then sustained. Methods: A "design, measure, analyze, improve, and control" quality improvement methodology requiring novel technology was used to try to improve PET/CT injection quality. Teams were educated on the importance of quality injections. Baseline infiltration rates were measured, center-specific associative factors were analyzed, team meetings were held, improvement plans were established and executed, and rates remeasured. To ensure that injection-quality gains were retained, real-time feedback and ongoing monitoring were used. Sustainability was assessed. Results: Seven centers and 56 technologists provided data on 5,541 injections. The centers' aggregated baseline infiltration rate was 6.2% (range, 2%-16%). On the basis of their specific associative factors, 4 centers developed improvement plans and reduced their aggregated infiltration rate from 8.9% to 4.6% ( P < 0.0001). Ongoing injection monitoring showed sustainability. Significant variation was found in center- and technologist-level infiltration rates ( P < 0.0001 and P = 0.0020, respectively). Conclusion: A quality improvement approach with new technology can help centers measure infiltration rates, determine associative factors, implement interventions, and improve and sustain injection quality. Because PET/CT images help guide patient management, the monitoring and improvement of radiotracer injection quality are important., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Tumors lack a well-regulated vascular supply of O 2 and often fail to balance O 2 supply and demand. Net O 2 tension within many tumors may not only depend on O 2 delivery but also depend strongly on O 2 demand. Thus, tumor O 2 consumption rates may influence tumor hypoxia up to true anoxia. Recent reports have shown that many human tumors in vivo depend primarily on oxidative phosphorylation (OxPhos), not glycolysis, for energy generation, providing a driver for consumptive hypoxia and an exploitable vulnerability. In this regard, IACS-010759 is a novel high affinity inhibitor of OxPhos targeting mitochondrial complex-I that has recently completed a Phase-I clinical trial in leukemia. However, in solid tumors, the effective translation of OxPhos inhibitors requires methods to monitor pharmacodynamics in vivo. Herein, 18 F-fluoroazomycin arabinoside ([ 18 F]FAZA), a 2-nitroimidazole-based hypoxia PET imaging agent, was combined with a rigorous test-retest imaging method for non-invasive quantification of the reversal of consumptive hypoxia in vivo as a mechanism-specific pharmacodynamic (PD) biomarker of target engagement for IACS-010759. Neither cell death nor loss of perfusion could account for the IACS-010759-induced decrease in [ 18 F]FAZA retention. Notably, in an OxPhos-reliant melanoma tumor, a titration curve using [ 18 F]FAZA PET retention in vivo yielded an IC 50 for IACS-010759 (1.4 mg/kg) equivalent to analysis ex vivo. Pilot [ 18 F]FAZA PET scans of a patient with grade IV glioblastoma yielded highly reproducible, high-contrast images of hypoxia in vivo as validated by CA-IX and GLUT-1 IHC ex vivo. Thus, [ 18 F]FAZA PET imaging provided direct evidence for the presence of consumptive hypoxia in vivo, the capacity for targeted reversal of consumptive hypoxia through the inhibition of OxPhos, and a highly-coupled mechanism-specific PD biomarker ready for translation., Competing Interests: The IACS-010759 patent is issued and held by UT MD Anderson Cancer Center.

The use of positron emission tomography (PET) in radiation therapy (RT) is rapidly increasing in the areas of staging, segmentation, treatment planning, and response assessment. The most common radiotracer is 18 F-fluorodeoxyglucose ([ 18 F]FDG), a glucose analog with demonstrated efficacy in cancer diagnosis and staging. However, diagnosis and RT planning are different endeavors with unique requirements, and very little literature is available for guiding physicists and clinicians in the utilization of [ 18 F]FDG-PET in RT. The two goals of this report are to educate and provide recommendations. The report provides background and education on current PET imaging systems, PET tracers, intensity quantification, and current utilization in RT (staging, segmentation, image registration, treatment planning, and therapy response assessment). Recommendations are provided on acceptance testing, annual and monthly quality assurance, scanning protocols to ensure consistency between interpatient scans and intrapatient longitudinal scans, reporting of patient and scan parameters in literature, requirements for incorporation of [ 18 F]FDG-PET in treatment planning systems, and image registration. The recommendations provided here are minimum requirements and are not meant to cover all aspects of the use of [ 18 F]FDG-PET for RT., (© 2019 American Association of Physicists in Medicine.)

Radiomics studies require many patients in order to power them, thus patients are often combined from different institutions and using different imaging protocols. Various studies have shown that imaging protocols affect radiomics feature values. We examined whether using data from cohorts with controlled imaging protocols improved patient outcome models. We retrospectively reviewed 726 CT and 686 PET images from head and neck cancer patients, who were divided into training or independent testing cohorts. For each patient, radiomics features with different preprocessing were calculated and two clinical variables-HPV status and tumor volume-were also included. A Cox proportional hazards model was built on the training data by using bootstrapped Lasso regression to predict overall survival. The effect of controlled imaging protocols on model performance was evaluated by subsetting the original training and independent testing cohorts to include only patients whose images were obtained using the same imaging protocol and vendor. Tumor volume, HPV status, and two radiomics covariates were selected for the CT model, resulting in an AUC of 0.72. However, volume alone produced a higher AUC, whereas adding radiomics features reduced the AUC. HPV status and one radiomics feature were selected as covariates for the PET model, resulting in an AUC of 0.59, but neither covariate was significantly associated with survival. Limiting the training and independent testing to patients with the same imaging protocol reduced the AUC for CT patients to 0.55, and no covariates were selected for PET patients. Radiomics features were not consistently associated with survival in CT or PET images of head and neck patients, even within patients with the same imaging protocol., Competing Interests: The authors have declared that no competing interests exist.

Radiomics studies require large patient cohorts, which often include patients imaged using different imaging protocols. We aimed to determine the impact of variability in imaging protocol parameters and interscanner variability using a phantom that produced feature values similar to those of patients. Positron emission tomography (PET) scans of a Hoffman brain phantom were acquired on GE Discovery 710, Siemens mCT, and Philips Vereos scanners. A standard-protocol scan was acquired on each machine, and then each parameter that could be changed was altered individually. The phantom was contoured with 10 regions of interest (ROIs). Values for 45 features with 2 different preprocessing techniques were extracted for each image. To determine the impact of each parameter on the reliability of each radiomics feature, the intraclass correlation coefficient (ICC) was calculated with the ROIs as the subjects and the parameter values as the raters. For interscanner comparisons, we compared the standard deviation of each radiomics feature value from the standard-protocol images to the standard deviation of the same radiomics feature from PET scans of 224 patients with non-small cell lung cancer. When the pixel size was resampled prior to feature extraction, all features had good reliability (ICC > 0.75) for the field of view and matrix size. The time per bed position had excellent reliability (ICC > 0.9) on all features. When the filter cutoff was restricted to values below 6 mm, all features had good reliability. Similarly, when subsets and iterations were restricted to reasonable values used in clinics, almost all features had good reliability. The average ratio of the standard deviation of features on the phantom scans to that of the NSCLC patient scans was 0.73 using fixed-bin-width preprocessing and 0.92 using 64-level preprocessing. Most radiomics feature values had at least good reliability when imaging protocol parameters were within clinically used ranges. However, interscanner variability was about equal to interpatient variability; therefore, caution must be used when combining patients scanned on equipment from different vendors in radiomics data sets., Competing Interests: The authors have declared that no competing interests exist.

First-order radiomic features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are associated with disease progression in early-stage classical Hodgkin lymphoma (HL). We hypothesized that a model incorporating first- and second-order radiomic features would more accurately predict outcome than MTV or TLG alone. We assessed whether radiomic features extracted from baseline PET scans predicted relapsed or refractory disease status in a cohort of 251 patients with stage I-II HL who were managed at a tertiary cancer center. Models were developed and tested using a machine-learning algorithm. Features extracted from mediastinal sites were highly predictive of primary refractory disease. A model incorporating 5 of the most predictive features had an area under the curve (AUC) of 95.2% and total error rate of 1.8%. By comparison, the AUC was 78% for both MTV and TLG and was 65% for maximum standardize uptake value (SUV max ). Furthermore, among the patients with refractory mediastinal disease, our model distinguished those who were successfully salvaged from those who ultimately died of HL. We conclude that our PET radiomic model may improve upfront stratification of early-stage HL patients with mediastinal disease and thus contribute to risk-adapted, individualized management.

Purpose: To examine the value of early changes in quantitative diffusion-weighted imaging and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for discriminating complete pathologic response (pCR) to chemoradiation in esophageal cancer., Methods and Materials: Twenty esophageal cancer patients treated with chemoradiation followed by surgery were prospectively enrolled. Patients underwent magnetic resonance imaging and FDG-PET/CT scans at baseline, interim (2 weeks after chemoradiation start), and first follow-up. On the basis of pathologic findings at surgery, patients were categorized into tumor regression groups (TRG1, TRG2, and TRG3+). Distributions of summary statistics in apparent diffusion coefficient (ADC) and FDG-PET at baseline and relative changes at interim and follow-up scans were compared between pCR/TRG1 and non-pCR/TRG2+ groups and across readers. Receiver operating characteristics were evaluated for summary measures to characterize discrimination of pCR from non-pCR., Results: Relative changes in tumor volume ADC (ΔADC) mean and 25th and 10th percentiles from baseline to interim were able to completely discriminate (area under the curve = 1, P < .0011) between pCR and non-pCR (thresholds = 27.7%, 29.2%, and 32.1%, respectively) and were found to have high interreader reliability (95% limits of agreement of 1.001, 0.944, and 0.940, respectively). Relative change in total lesion glycolysis (TLG) from baseline to interim was significantly different among pCR and non-pCR groups (P=.0117) and yielded an area under the curve of 0.947 (95% confidence interval 0.8505-1.043). An optimal threshold of 59% decrease in TLG provided optimal sensitivity (specificity) of 1.000 (0.867). Changes in ADC summary measures were negatively correlated with that of TLG (Spearman, -0.495, P=.027)., Conclusions: Quantitative volume ΔADC and TLG during treatment may serve as early imaging biomarkers for discriminating pathologic response to chemoradiation in esophageal cancer. Validation of these data in larger, prospective, multicenter studies is essential., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Our aim is to evaluate in phantom and patient studies a recently developed elastic motion debluring (EMDB) technique which makes use of all the acquired PET data and compare its performance to other conventional techniques such as phase based gating (PBG) and HDChest (HDC) both of which use fractions of the acquired data. Comparisons were made with respect to static whole-body (SWB) images with no motion correction. Methods: A phantom simulating respiratory motion of the thorax with lung lesions (5 spheres with ID=10- 28 mm) was scanned with 0, 1, 2, and 3 cm motion. Four reconstructions were performed: SWB, PBG, HDC, and EMDB. For PBG, the average (PBGave) and maximum bin (PBGmax) were used. To compare the reconstructions, the ratios of SUV max (RSmax), SUVpeak (RSpeak), and CNR (RCNR) were calculated with respect to SWB. Additionally, 46 patients with lung or liver tumors < 3 cm diameter were also studied. Measurements of SUV max , SUVpeak, and contrast-to-noise ratio (CNR) were made for 46 lung and 19 liver lesions. To evaluate image noise, the SUV standard deviation was measured in healthy lung and liver tissue and in the phantom background. Finally, subjective image quality of patient exams was scored on a 5 point scale by four radiologists. Results: In the phantom, EMDB increased SUV max /SUVpeak over SWB but to a lesser extent than the other reconstruction methodologies. The RCNR for EMDB however was higher than all other reconstructions (0.68 EMDB > 0.54 HDC > 0.41 PBGmax > 0.31 PBGave). Similar results were seen in patient studies. The SUV max /SUVpeak were higher by 19.3/11.1% EMDB, 21.6/13.9% HDC, 22.8/12.8% PBGave, and 45.6/26.8% PBGmax compared to SWB. Lung/liver noise increased EMDB (3/15%), HDC (35/56%), PBGave (100/170%), and PBGmax (146/219%). CNR increased in lung/liver tumors only for EMDB (18/13%), and decreased for HDC (-14/-23%), PBGave (-39/-63%), and PBGmax (-18/-46%). Average radiologist scores of image quality were SWB (4.0 ± 0.8) > EMDB (3.7 ± 1.0) > HDC (3.1 ± 1.0) > PBG (1.5 ± 0.7). Conclusion: The EMDB algorithm had the least increase in image noise, improved lesion CNR, and had the highest overall image quality score., (Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Dose-adjusted rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH) has produced good outcomes in primary mediastinal B-cell lymphoma (PMBCL), but predictors of resistance to this treatment are unclear. We investigated whether [ 18 F]fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) findings could identify patients with PMBCL who would not respond completely to DA-R-EPOCH. We performed a retrospective analysis of 65 patients with newly diagnosed stage I to IV PMBCL treated at 2 tertiary cancer centers who had PET-CT scans available before and after frontline therapy with DA-R-EPOCH. Pretreatment variables assessed included metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Optimal cutoff points for progression-free survival (PFS) were determined by a machine learning approach. Univariate and multivariable models were constructed to assess associations between radiographic variables and PFS. At a median follow-up of 36.6 months (95% confidence interval, 28.1-45.1), 2-year PFS and overall survival rates for the 65 patients were 81.4% and 98.4%, respectively. Machine learning-derived thresholds for baseline MTV and TLG were associated with inferior PFS (elevated MTV: hazard ratio [HR], 11.5; P = .019; elevated TLG: HR, 8.99; P = .005); other pretreatment clinical factors, including International Prognostic Index and bulky (>10 cm) disease, were not. On multivariable analysis, only TLG retained statistical significance ( P = .049). Univariate analysis of posttreatment variables revealed that residual CT tumor volume, maximum standardized uptake value, and Deauville score were associated with PFS; a Deauville score of 5 remained significant on multivariable analysis ( P = .006). A model combining baseline TLG and end-of-therapy Deauville score identified patients at increased risk of progression., (© 2018 by The American Society of Hematology.)

The presence of bulky disease in Hodgkin lymphoma (HL), traditionally defined with a 1-dimensional measurement, can change a patient's risk grouping and thus the treatment approach. We hypothesized that 3-dimensional measurements of disease burden obtained from baseline 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scans, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), would more accurately risk-stratify patients. To test this hypothesis, we reviewed pretreatment PET-CT scans of patients with stage I-II HL treated at our institution between 2003 and 2013. Disease was delineated on prechemotherapy PET-CT scans by 2 methods: (1) manual contouring and (2) subthresholding of these contours to give the tumor volume with standardized uptake value ≥2.5. MTV and TLG were extracted from the threshold volumes (MTV t , TLG t ) and from the manually contoured soft-tissue volumes. At a median follow-up of 4.96 years for the 267 patients evaluated, 27 patients were diagnosed with relapsed or refractory disease and 12 died. Both MTV t and TLG t were highly correlated with freedom from progression and were dichotomized with 80th percentile cutoff values of 268 and 1703, respectively. Consideration of MTV and TLG enabled restratification of early unfavorable HL patients as having low- and high-risk disease. We conclude that MTV and TLG provide a potential measure of tumor burden to aid in risk stratification of early unfavorable HL patients., (© 2018 by The American Society of Hematology.)

Early-stage classical Hodgkin lymphoma (HL) patients are evaluated by an end-of-chemotherapy positron emission tomography-computed tomography (eoc-PET-CT) after doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and before radiation therapy (RT). We determined freedom from progression (FFP) in patients treated with ABVD and RT according to the eoc-PET-CT 5-point score (5PS). Secondarily, we assessed whether patients with a positive eoc-PET-CT (5PS of 4-5) can be cured with RT alone. The cohort comprised 174 patients treated for stage I-II HL with ABVD and RT alone. ABVD was given with a median of four cycles and RT with a median dose of 30·6 Gy. Five-year FFP was 97%. Five-year FFP was 100% (0 relapses/98 patients) for patients with a 5PS of 1-2, 97% (2/65) for a 5PS of 3, 83% (1/8) for a 5PS of 4, and 67% (1/3) for a 5PS of 5 (P < 0·001). Patients with positive eoc-PET-CT scans who were selected for salvage RT alone had experienced a very good partial response to ABVD. Risk factors for recurrence in this subgroup included a small reduction in tumour size and a 'bounce' in ≥1 PET-CT parameter (reduction then rise from interim to final scan). Thus, a positive eoc-PET-CT is associated with inferior FFP; however, appropriately selected patients can be cured with RT alone., (© 2017 John Wiley & Sons Ltd.)

Purpose: In early-stage classical Hodgkin lymphoma, fluorodeoxyglucose positron emission tomography (PET)-computed tomography (CT) scans are performed routinely after chemotherapy, and the 5-point Deauville score is used to report the disease response. We hypothesized that other PET-CT parameters, considered in combination with Deauville score, would improve risk stratification., Methods and Materials: Patients treated for stage I to II Hodgkin lymphoma from 2003 to 2013, who were aged ≥18 years and had analyzable PET-CT scans performed before and after chemotherapy, were eligible. The soft tissue volume (STV), maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis were recorded from the PET-CT scans before and after chemotherapy. Reductions were defined as 1 - (final PET-CT value)/(corresponding initial PET-CT value). The primary endpoint was freedom from progression (FFP)., Results: For 202 patients treated with chemotherapy with or without radiation therapy, the 5-year FFP was 89% (95% confidence interval 85%-93%). All PET-CT parameters were strongly associated with the Deauville score (P<.001) and FFP (P<.0001) on univariate analysis. The Deauville score was highly predictive of FFP (C-index 0.89) but was less discriminating in the Deauville 1 to 4 subset (C-index 0.67). Therefore, we aimed to identify PET-CT parameters that would improve risk stratification for this subgroup (n=187). STV reduction was predictive of outcome (C-index 0.71) and was dichotomized with an optimal cutoff of 0.65 (65% reduction in STV). A model incorporating the Deauville score and STV reduction predicted FFP more accurately than either measurement alone in the Deauville 1 to 4 subset (C-index 0.83). The improvement in predictive accuracy of this composite measure compared with the Deauville score alone met statistical significance (P=.045)., Conclusions: The relative reduction in tumor size is an independent predictor of outcome. Combined with the Deauville score, it might improve risk stratification and contribute to response-adapted individualization of therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aims of this study were to evaluate the effects of noise, motion blur, and motion compensation using quiescent-period gating (QPG) on the activity concentration (AC) distribution-quantified using the cumulative AC volume histogram (ACVH)-in count-limited studies such as 90 Y-PET/CT. An International Electrotechnical Commission phantom filled with low 18 F activity was used to simulate clinical 90 Y-PET images. PET data were acquired using a GE-D690 when the phantom was static and subject to 1-4 cm periodic 1D motion. The static data were down-sampled into shorter durations to determine the effect of noise on ACVH. Motion-degraded PET data were sorted into multiple gates to assess the effect of motion and QPG on ACVH. Errors in ACVH at AC 90 (minimum AC that covers 90% of the volume of interest (VOI)), AC 80 , and AC mean (average AC in the VOI) were characterized as a function of noise and amplitude before and after QPG. Scan-time reduction increased the apparent non-uniformity of sphere doses and the dispersion of ACVH. These effects were more pronounced in smaller spheres. Noise-related errors in ACVH at AC 20 to AC 70 were smaller (<15%) compared to the errors between AC 80 to AC 90 (>15%). The accuracy of AC mean was largely independent of the total count. Motion decreased the observed AC and skewed the ACVH toward lower values; the severity of this effect depended on motion amplitude and tumor diameter. The errors in AC 20 to AC 80 for the 17 mm sphere were  -25% and  -55% for motion amplitudes of 2 cm and 4 cm, respectively. With QPG, the errors in AC 20 to AC 80 of the 17 mm sphere were reduced to  -15% for motion amplitudes  <4 cm. For spheres with motion amplitude to diameter ratio  >0.5, QPG was effective at reducing errors in ACVH despite increases in image non-uniformity due to increased noise. ACVH is believed to be more relevant than mean or maximum AC to calculate tumor control and normal tissue complication probability. However, caution needs to be exercised when using ACVH in post-therapy 90 Y imaging because of its susceptibility to image degradation from both image noise and respiratory motion.

Purpose: Bleomycin pulmonary toxicity (BPT) is a well-known complication of treatment in patients with Hodgkin lymphoma (HL). We undertook the present study to investigate the risk of radiation pneumonitis (RP) in the setting of BPT and to determine the need for delay or omission of radiation therapy (RT) in these patients., Methods and Materials: We identified 123 HL patients treated with ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) followed by RT to the chest from January 2009 to December 2014. The medical records were reviewed for clinical, pathologic, and treatment information and toxicities. Our primary outcome was RP of any grade. Univariate and multivariate analyses were used to assess the association of BPT, baseline patient characteristics, and treatment variables with the incidence of RP., Results: A total of 123 patients were included, of whom 99 (80%) received consolidation intensity modulated RT after ABVD treatment. We identified 31 patients (25.2%) with BPT after frontline ABVD. Seventeen patients (13.8%) developed RP a median of 8 weeks (range 1-39) after RT completion. BPT did not correlate with the risk of developing RP (P=.36). We evaluated the RP outcomes with respect to the bleomycin to RT interval (≤6 weeks vs >6 weeks), and we found that this interval did not predict for RP risk (P=.60). Dosimetric parameters such as the volume covered by 5 Gy and the mean lung dose were analyzed. A volume covered by 5 Gy of >55% and mean lung dose >13.5 Gy increased the risk of RP by 1.14-fold (P=.002) and 4.24-fold (P=.007), respectively., Conclusions: The results of our study suggest that BPT does not increase the risk of developing RP. Furthermore, RT initiation does not need to be delayed after chemotherapy, except to allow for the completion of steroid therapy or clinical recovery from BPT., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT])., Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated., Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease., Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Gold nanoparticles (GNPs) are being investigated actively for various applications in cancer diagnosis and therapy. As an effort to improve the imaging of GNPs in vivo, the authors developed bimetallic hybrid Zn@Au NPs with zinc cores and gold shells, aiming to render them in vivo visibility through positron emission tomography (PET) after the proton activation of the zinc core as well as capability to induce radiosensitization through the secondary electrons produced from the gold shell when irradiated by various radiation sources., Methods: Nearly spherical zinc NPs (∼5-nm diameter) were synthesized and then coated with a ∼4.25-nm gold layer to make Zn@Au NPs (∼13.5-nm total diameter). 28.6 mg of these Zn@Au NPs was deposited (∼100 μm thick) on a thin cellulose target and placed in an aluminum target holder and subsequently irradiated with 14.15-MeV protons from a GE PETtrace cyclotron with 5-μA current for 5 min. After irradiation, the cellulose matrix with the NPs was placed in a dose calibrator to assess the induced radioactivity. The same procedure was repeated with 8-MeV protons. Gamma ray spectroscopy using an high-purity germanium detector was conducted on a very small fraction (<1 mg) of the irradiated NPs for each proton energy. In addition to experimental measurements, Monte Carlo simulations were also performed with radioactive Zn@Au NPs and solid GNPs of the same size irradiated with 160-MeV protons and 250-kVp x-rays., Results: The authors measured 168 μCi of activity 32 min after the end of bombardment for the 14.15-MeV proton energy sample using the (66)Ga setting on a dose calibrator; activity decreased to 2 μCi over a 24-h period. For the 8-MeV proton energy sample, PET imaging was additionally performed for 5 min after a 12-h delay. A 12-h gamma ray spectrum showed strong peaks at 511 keV (2.05 × 10(6) counts) with several other peaks of smaller magnitude for each proton energy sample. PET imaging showed strong PET signals from mostly decaying (66)Ga. The Monte Carlo results showed that radioactive Zn@Au NPs and solid GNPs provided similar characteristics in terms of their secondary electron spectra when irradiated., Conclusions: The Zn@Au NPs developed in this investigation have the potential to be used as PET-imageable radiosensitizers for radiotherapy applications as well as PET tracers for molecular imaging applications.

Biocompatible/biodegradable hydrogel polymers were immersed in 18O-enriched water and 16O-water to create 18O-water hydrogels and 16O-water hydrogels. In both cases, the hydrogels were made of ~91 wt% water and ~9 wt% polymer. In addition, 5-8 μm Zn powder was suspended in 16O-water and 18O-enriched water and cross-linked with hydrogel polymers to create Zn/16O-water hydrogels (30/70 wt%, ~9 wt% polymer) and Zn/18O-water hydrogels (10/90 wt%), respectively. A block of extra-firm 'wet' tofu (12.3 × 8.8 × 4.9 cm, ρ  ≈  1.05 g cm−3) immersed in water was injected with Zn/16O-water hydrogels (0.9 ml each) at four different depths using an 18-gauge needle. Similarly, Zn/18O-water hydrogels (0.9 ml) were injected into a second tofu phantom. As a reference, both 16O-water hydrogels (1.8 ml) and 18O-water hydrogels (0.9 ml) in Petri dishes were irradiated in a 'dry' environment. The hydrogels in the wet tofu phantoms and dry Petri dishes were scanned via CT and images were used for treatment planning. Then, they were positioned at the proton distal dose fall-off region and irradiated (2 Gy) followed by PET/CT imaging.Notably high PET signals were observed only in 18O-water hydrogels in the dry environment. The visibility of the Zn/16O-water hydrogels injected into the tofu phantom was outstanding in CT images, but these hydrogels provided no noticeable PET signals. The visibility of the Zn/18O-water hydrogels in the wet tofu were excellent on CT and moderate on PET; however, the PET signals were weaker than those in the dry environment, possibly owing to 18O-water leaching out. The hydrogel markers studied here could be used to develop universal PET/CT fiducial markers. Their PET visibility (attributed more to activated 18O-water than Zn) after proton irradiation can be used for proton therapy/range verification. More investigation is needed to slow down the leaching of 18O-water.

Purpose: To determine whether previously identified quantitative image features (QIFs) based on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) (co-occurrence matrix energy and solidity) are able to isolate subgroups of patients who would receive a benefit or detriment from dose escalation in terms of overall survival (OS) or progression-free survival (PFS)., Methods and Materials: Subgroups of a previously analyzed 225 patient cohort were generated with the use of 5-percentile increment cutoff values of disease solidity and primary tumor co-occurrence matrix energy. The subgroups were analyzed with a log-rank test to determine whether there was a difference in OS and PFS between patients treated with 60 to 70 Gy and those receiving 74 Gy., Results: In the entire patient cohort, there was no statistical difference in terms of OS or PFS between patients receiving 74 Gy and those receiving 60 to 70 Gy. It was qualitatively observed that as disease solidity and primary co-occurrence matrix energy increased, patients receiving 74 Gy had an improved OS and PFS compared with those receiving 60 to 70 Gy. The opposite trend (detriment of receiving 74 Gy) was also observed regarding low values of disease solidity and primary co-occurrence matrix energy., Conclusions: FDG-PET-based QIFs were found to be capable of isolating subgroups of patients who received a benefit or detriment from dose escalation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Combining image-guided therapy techniques for the treatment of liver cancers is a strategy that is being used to improve local tumor control rates. Here, we evaluate the intratumoral uptake of nanoparticles used in combination with radiofrequency ablation (RFA), irreversible electroporation (IRE), or laser induced thermal therapy (LITT). Eight rabbits with VX2 tumor in the liver underwent one of four treatments: (i) nanoembolization (NE) with radiolabeled, hollow gold nanoparticles loaded with doxorubicin (⁶⁴Cu-PEG-HAuNS-DOX); (ii) NE + RFA; (iii) NE + IRE; (iv) NE +LITT. Positron emission tomography/computed tomography (PET/CT) imaging was obtained 1-hr or 18-hrs after intervention. Tissue samples were collected for autoradiography and transmission electron microscopy (TEM) analysis. PET/CT imaging at 1-hr showed focal deposition of oil and nanoparticles in the tumor only after NE+ RFA but at 18-hrs, all animals had focal accumulation of oil and nanoparticles in the tumor region. Autoradiograph analysis demonstrated nanoparticle deposition in the tumor and in the ablated tissues adjacent to the tumor when NE was combined with ablation. TEM results showed the intracellular uptake of nanoparticles in tumor only after NE + IRE. Nanoparticles demonstrated a structural change, suggesting direct interaction, potentially leading to drug release, only after NE + LITT. The findings demonstrate that a combined NE and ablation treatment technique for liver tumors is feasible, resulting in deposition of nanoparticles in and around the tumor. Depending on the ablative energy applied, different effects are seen on nanoparticle localization and structure. These effects should be considered when designing nanoparticles for use in combination with ablation technologies., Competing Interests: The authors report no conflicts of interest in this work.

Purpose: To determine whether quantitative imaging features from pretreatment positron emission tomography (PET) can enhance patient overall survival risk stratification beyond what can be achieved with conventional prognostic factors in patients with stage III non-small cell lung cancer (NSCLC)., Materials and Methods: The institutional review board approved this retrospective chart review study and waived the requirement to obtain informed consent. The authors retrospectively identified 195 patients with stage III NSCLC treated definitively with radiation therapy between January 2008 and January 2013. All patients underwent pretreatment PET/computed tomography before treatment. Conventional PET metrics, along with histogram, shape and volume, and co-occurrence matrix features, were extracted. Linear predictors of overall survival were developed from leave-one-out cross-validation. Predictive Kaplan-Meier curves were used to compare the linear predictors with both quantitative imaging features and conventional prognostic factors to those generated with conventional prognostic factors alone. The Harrell concordance index was used to quantify the discriminatory power of the linear predictors for survival differences of at least 0, 6, 12, 18, and 24 months. Models were generated with features present in more than 50% of the cross-validation folds., Results: Linear predictors of overall survival generated with both quantitative imaging features and conventional prognostic factors demonstrated improved risk stratification compared with those generated with conventional prognostic factors alone in terms of log-rank statistic (P = .18 vs P = .0001, respectively) and concordance index (0.62 vs 0.58, respectively). The use of quantitative imaging features selected during cross-validation improved the model using conventional prognostic factors alone (P = .007). Disease solidity and primary tumor energy from the co-occurrence matrix were found to be selected in all folds of cross-validation., Conclusion: Pretreatment PET features were associated with overall survival when adjusting for conventional prognostic factors in patients with stage III NSCLC., (© RSNA, 2015.)

Compressed sensing (CS) aims to recover images from fewer measurements than that governed by the Nyquist sampling theorem. Most CS methods use analytical predefined sparsifying domains such as total variation, wavelets, curvelets, and finite transforms to perform this task. In this study, we evaluated the use of dictionary learning (DL) as a sparsifying domain to reconstruct PET images from partially sampled data, and compared the results to the partially and fully sampled image (baseline).A CS model based on learning an adaptive dictionary over image patches was developed to recover missing observations in PET data acquisition. The recovery was done iteratively in two steps: a dictionary learning step and an image reconstruction step. Two experiments were performed to evaluate the proposed CS recovery algorithm: an IEC phantom study and five patient studies. In each case, 11% of the detectors of a GE PET/CT system were removed and the acquired sinogram data were recovered using the proposed DL algorithm. The recovered images (DL) as well as the partially sampled images (with detector gaps) for both experiments were then compared to the baseline. Comparisons were done by calculating RMSE, contrast recovery and SNR in ROIs drawn in the background, and spheres of the phantom as well as patient lesions.For the phantom experiment, the RMSE for the DL recovered images were 5.8% when compared with the baseline images while it was 17.5% for the partially sampled images. In the patients' studies, RMSE for the DL recovered images were 3.8%, while it was 11.3% for the partially sampled images. Our proposed CS with DL is a good approach to recover partially sampled PET data. This approach has implications toward reducing scanner cost while maintaining accurate PET image quantification.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [(64)Cu]CuS NPs, in which the radiotherapeutic property of (64)Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG-[(64)Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[(64)Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[(64)Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Most positron emission tomography/computed tomography (PET/CT) scanners consist of tightly packed discrete detector rings to improve scanner efficiency. The authors' aim was to use compressive sensing (CS) techniques in PET imaging to investigate the possibility of decreasing the number of detector elements per ring (introducing gaps) while maintaining image quality., Methods: A CS model based on a combination of gradient magnitude and wavelet domains (wavelet-TV) was developed to recover missing observations in PET data acquisition. The model was designed to minimize the total variation (TV) and L1-norm of wavelet coefficients while constrained by the partially observed data. The CS model also incorporated a Poisson noise term that modeled the observed noise while suppressing its contribution by penalizing the Poisson log likelihood function. Three experiments were performed to evaluate the proposed CS recovery algorithm: a simulation study, a phantom study, and six patient studies. The simulation dataset comprised six disks of various sizes in a uniform background with an activity concentration of 5:1. The simulated image was multiplied by the system matrix to obtain the corresponding sinogram and then Poisson noise was added. The resultant sinogram was masked to create the effect of partial detector removal and then the proposed CS algorithm was applied to recover the missing PET data. In addition, different levels of noise were simulated to assess the performance of the proposed algorithm. For the phantom study, an IEC phantom with six internal spheres each filled with F-18 at an activity-to-background ratio of 10:1 was used. The phantom was imaged twice on a RX PET/CT scanner: once with all detectors operational (baseline) and once with four detector blocks (11%) turned off at each of 0 ˚, 90 ˚, 180 ˚, and 270° (partially sampled). The partially acquired sinograms were then recovered using the proposed algorithm. For the third test, PET images from six patient studies were investigated using the same strategy of the phantom study. The recovered images using WTV and TV as well as the partially sampled images from all three experiments were then compared with the fully sampled images (the baseline). Comparisons were done by calculating the mean error (%bias), root mean square error (RMSE), contrast recovery (CR), and SNR of activity concentration in regions of interest drawn in the background as well as the disks, spheres, and lesions., Results: For the simulation study, the mean error, RMSE, and CR for the WTV (TV) recovered images were 0.26% (0.48%), 2.6% (2.9%), 97% (96%), respectively, when compared to baseline. For the partially sampled images, these results were 22.5%, 45.9%, and 64%, respectively. For the simulation study, the average SNR for the baseline was 41.7 while for WTV (TV), recovered image was 44.2 (44.0). The phantom study showed similar trends with 5.4% (18.2%), 15.6% (18.8%), and 78% (60%), respectively, for the WTV (TV) images and 33%, 34.3%, and 69% for the partially sampled images. For the phantom study, the average SNR for the baseline was 14.7 while for WTV (TV) recovered image was 13.7 (11.9). Finally, the average of these values for the six patient studies for the WTV-recovered, TV, and partially sampled images was 1%, 7.2%, 92% and 1.3%, 15.1%, 87%, and 27%, 25.8%, 45%, respectively., Conclusions: CS with WTV is capable of recovering PET images with good quantitative accuracy from partially sampled data. Such an approach can be used to potentially reduce the cost of scanners while maintaining good image quality.

Purpose: To determine whether pretreatment CT texture features can improve patient risk stratification beyond conventional prognostic factors (CPFs) in stage III non-small cell lung cancer (NSCLC)., Methods and Materials: We retrospectively reviewed 91 cases with stage III NSCLC treated with definitive chemoradiation therapy. All patients underwent pretreatment diagnostic contrast enhanced computed tomography (CE-CT) followed by 4-dimensional CT (4D-CT) for treatment simulation. We used the average-CT and expiratory (T50-CT) images from the 4D-CT along with the CE-CT for texture extraction. Histogram, gradient, co-occurrence, gray tone difference, and filtration-based techniques were used for texture feature extraction. Penalized Cox regression implementing cross-validation was used for covariate selection and modeling. Models incorporating texture features from the 33 image types and CPFs were compared to those with models incorporating CPFs alone for overall survival (OS), local-regional control (LRC), and freedom from distant metastases (FFDM). Predictive Kaplan-Meier curves were generated using leave-one-out cross-validation. Patients were stratified based on whether their predicted outcome was above or below the median. Reproducibility of texture features was evaluated using test-retest scans from independent patients and quantified using concordance correlation coefficients (CCC). We compared models incorporating the reproducibility seen on test-retest scans to our original models and determined the classification reproducibility., Results: Models incorporating both texture features and CPFs demonstrated a significant improvement in risk stratification compared to models using CPFs alone for OS (P=.046), LRC (P=.01), and FFDM (P=.005). The average CCCs were 0.89, 0.91, and 0.67 for texture features extracted from the average-CT, T50-CT, and CE-CT, respectively. Incorporating reproducibility within our models yielded 80.4% (±3.7% SD), 78.3% (±4.0% SD), and 78.8% (±3.9% SD) classification reproducibility in terms of OS, LRC, and FFDM, respectively., Conclusions: Pretreatment tumor texture may provide prognostic information beyond that obtained from CPFs. Models incorporating feature reproducibility achieved classification rates of ∼80%. External validation would be required to establish texture as a prognostic factor., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy)., Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings., Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET-) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET- versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET- vs 52% PET+ [P=.012], OS 78% for PET- and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET- vs 81% PET+ [P=.88]; OS 90% PET- vs 81% PET+ [P=.39])., Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Positron emission mammography (PEM) has better spatial resolution than positron emission tomography/computed tomography (PET/CT), or PET/CT. We evaluated the feasibility of extremity imaging with PEM using PET as a standard., Methods/materials: Fourteen patients underwent sequential PET/CT and PEM., Results/discussion: PEM visualized with equal or improved resolution all of the lesions identified on PET/CT. It often provided additional information such improved uptake localization and also visualized activity in an adjacent structures that was not seen on PET/CT or magnetic resonance imaging. We believe PEM can image the extremities in diseases like melanoma, arthritis and osteomyelitis and patients with metallic hardware., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Owing to its unique configuration of two adjustable plate detectors positron emission mammography, or PEM, could theoretically also function as a high-resolution positron emission scanner for the extremities or neck. PEM quantitates its activity via a "PEM uptake value," or PUV, and although its relationship to the standardized uptake value, or SUV, has been demonstrated in the breasts, to our knowledge there are no studies validating PUV in other sites such as the extremities., Materials and Methods: This was a retrospective chart review of two separate protocols of a total of 15 patients. The patients all had hypermetabolic lesions in the extremities or neck on imaging with PET/CT and were sent after their PET/CT to PEM for further imaging. Owing to the sequential nature of these examinations no additional radiotracer was administered., Results: Spearman's rank order correlation was calculated between the PUVmax obtained from PEM images, and the SUVmax for all. Spearman's rank order correlation for all sites was 0.42, which is not significantly different from 0 (p = 0.13). When neck lesions were excluded from the group, there was a strong and statistically significant correlation between PUVmax and SUVmax, with Spearman's rank correlation of 0.73, and significantly different from 0 (p = 0.0068)., Discussion: The correlation of PUV and SUV in the extremities indicates the potential use of PEM as a semiquantitative, high-resolution positron emission scanner and warrants further investigation, especially in the realms of disease processes that often present in the extremities, such as melanoma, osteomyelitis, and arthritis, as well as playing a role in the imaging of patients with metallic hardware post-limb salvage surgery.

Positron emission tomography computed tomography(PET-CT) imaging has emerged as an essential clinical diagnostic tool in the evaluation of thoracic abnormalities. Currently, its primary role is for tumor imaging; it helps to differentiate benign from malignant nodules, stage tumors, determine response, and follow patients after therapy is complete. It has also been used for nononcologic diseases, but the indications are less well defined. PET is a fundamental component of the molecular imaging initiative, and as new more specific imaging probes and better instrumentation are developed, PET-CT is certain to improve diagnostic accuracy and become even more integrated into the imaging armamentarium., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

PET/CT is widely used in the staging and assessment of therapeutic response in patients with malignancies. Accurate interpretation of PET/CT requires knowledge of the normal physiologic distribution of [18F]-fluoro-2-deoxy-d-glucose, artifacts due to the use of CT for attenuation correction of the PET scan and potential pitfalls due to malignancies that are PET negative and benign conditions that are PET positive. Awareness of these artifacts and potential pitfalls is important in preventing misinterpretation that can alter patient management., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Response to primary treatment in diffuse large B-cell lymphoma (DLBCL) is highly predictive of long-term outcome. We evaluated the value of computed tomography (CT) findings relative to positron emission tomography (PET) findings, after the completion of chemotherapy. We retrospectively reviewed records from 491 patients with DLBCL at M. D. Anderson in 2001-2007; 22 patients were excluded for uncertain pathology and 169 for having received consolidative radiation, leaving 300 patients for the present analysis (median age, 61 years; 53% men, 47% women; 27% stage I-II, 73% stage III-IV; 73% completed 6-8 cycles of doxorubicin-based therapy). Factors associated with outcome on univariate analysis were response according to PET/CT and CT (p < 0.0001 for overall survival [OS], disease-specific survival [DSS] and progression-free survival [PFS]); number of chemotherapy cycles received (p < 0.0001 OS, p < 0.0001 DSS, p < 0.002 PFS); the combined presence of Ki-67 > 50%, PET SUV ≥ 13 and bulky (> 5 cm) disease (p = 0.005 OS, p = 0.001 DSS, p = 0.001 PFS); and International Prognostic Index (IPI) score (p = 0.004 OS, p = 0.005 DSS, p = 0.004 PFS). On multivariate analysis, PET/CT-negative, CT residual mass (> 2 cm) significantly influenced OS, DSS and PFS (p < 0.0001). The presence of a residual mass >2 cm on CT, coupled with negative findings on PET/CT, has prognostic value in DLBCL.

Proton beam range verification using positron emission tomography (PET) currently relies on proton activation of tissue, the products of which decay with a short half-life and necessitate an on-site PET scanner. Tissue activation is, however, negligible near the distal dose fall-off region of the proton beam range due to their high interaction energy thresholds. Therefore Monte Carlo simulation is often supplemented for comparison with measurement; however, this also may be associated with systematic and statistical uncertainties. Therefore, we sought to test the feasibility of using long-lived proton-activated external materials that are inserted or infused into the target volume for more accurate proton beam range verification that could be performed at an off-site PET scanner. We irradiated samples of ≥98% (18)O-enriched water, natural Cu foils, and >97% (68)Zn-enriched foils as candidate materials, along with samples of tissue-equivalent materials including (16)O water, heptane (C7H16), and polycarbonate (C16H14O3)n, at four depths (ranging from 100% to 3% of center of modulation (COM) dose) along the distal fall-off of a modulated 160 MeV proton beam. Samples were irradiated either directly or after being embedded in Plastic Water® or balsa wood. We then measured the activity of the samples using PET imaging for 20 or 30 min after various delay times. Measured activities of candidate materials were up to 100 times greater than those of the tissue-equivalent materials at the four distal dose fall-off depths. The differences between candidate materials and tissue-equivalent materials became more apparent after longer delays between irradiation and PET imaging, due to the longer half-lives of the candidate materials. Furthermore, the activation of the candidate materials closely mimicked the distal dose fall-off with offsets of 1 to 2 mm. Also, signals from the foils were clearly visible compared to the background from the activated Plastic Water® and balsa wood phantoms. These results indicate that markers made from these candidate materials could be used for in vivo proton range verification using an off-site PET scanner.

Objective: The objective of our study was to assess whether CT features and FDG up-take of primary salivary gland-type tumors of the lung are associated with tumor type, disease stage, or survival., Materials and Methods: CT (n = 30) and PET (n = 15) data of 30 consecutive patients with primary salivary gland-type tumors of the lung were retrospectively evaluated for tumor size, location, and homogeneity and the presence of lymphadenopathy, pleural effusions, and metastases. Maximum FDG uptake and volumetric FDG uptake of the tumors were recorded. The Wilcoxon rank sum and Fisher exact tests and univariate Cox regression were used for statistical calculations., Results: Compared with mucoepidermoid carcinomas, adenoid cystic carcinomas (57%) were larger (mean, 3.5 vs 2.2 cm, respectively; p = 0.03), more frequently involved the central airways (94% vs 63%; p = 0.002), and had a higher median FDG uptake (p = 0.0264). Higher FDG uptake of the primary tumor was associated with nodal tumor involvement (p = 0.05). The median overall survival times for patients with adenoid cystic carcinoma and mucoepidermoid carcinoma were 7.7 and 4.0 years, respectively. Imaging features that significantly affected overall survival included the presence of mediastinal or hilar lymphadenopathy (hazard ratio [HR], 4.33; 95% CI, 1.15-16.26; p = 0.03), suspected metastatic disease (HR, 5.10; 95% CI, 1.27-20.47; p = 0.02), and primary tumor heterogeneity (HR, 3.46; 95% CI, 1.04-11.55; p = 0.04)., Conclusion: Higher FDG uptake is associated with nodal disease in patients with primary salivary gland-type tumors of the lung but is not predictive of survival, whereas CT features suggestive of advanced disease correlate with worse outcome.

Positron emission tomography (PET) has been suggested as an imaging technique for in vivo proton dose and range verification after proton induced-tissue activation. During proton treatment, irradiated tissue is activated and decays while emitting positrons. In this paper, we assessed the feasibility of using PET imaging after proton treatment to determine tissue elemental composition by evaluating the resultant composite decay curve of activated tissue. A phantom consisting of sections composed of different combinations of (1)H, (12)C, (14)N, and (16)O was irradiated using a pristine Bragg peak and a 6 cm spread-out Bragg-peak (SOBP) proton beam. The beam ranges defined at 90% distal dose were 10 cm; the delivered dose was 1.6 Gy for the near monoenergetic beam and 2 Gy for the SOBP beam. After irradiation, activated phantom decay was measured using an in-room PET scanner for 30 min in list mode. Decay curves from the activated (12)C and (16)O sections were first decomposed into multiple simple exponential decay curves, each curve corresponding to a constituent radioisotope, using a least-squares method. The relative radioisotope fractions from each section were determined. These fractions were used to guide the decay curve decomposition from the section consisting mainly of (12)C + (16)O and calculate the relative elemental composition of (12)C and (16)O. A Monte Carlo simulation was also used to determine the elemental composition of the (12)C + (16)O section. The calculated compositions of the (12)C + (16)O section using both approaches (PET and Monte Carlo) were compared with the true known phantom composition. Finally, two patients were imaged using an in-room PET scanner after proton therapy of the head. Their PET data and the technique described above were used to construct elemental composition ((12)C and (16)O) maps that corresponded to the proton-activated regions. We compared the (12)C and (16)O compositions of seven ROIs that corresponded to the vitreous humor, adipose/face mask, adipose tissue, and brain tissue with ICRU 46 elemental composition data. The (12)C and (16)O compositions of the (12)C + (16)O phantom section were estimated to within a maximum difference of 3.6% for the near monoenergetic and SOBP beams over an 8 cm depth range. On the other hand, the Monte Carlo simulation estimated the corresponding (12)C and (16)O compositions in the (12)C + (16)O section to within a maximum difference of 3.4%. For the patients, the (12)C and (16)O compositions in the seven ROIs agreed with the ICRU elemental composition data, with a mean (maximum) difference of 9.4% (15.2%). The (12)C and (16)O compositions of the phantom and patients were estimated with relatively small differences. PET imaging may be useful for determining the tissue elemental composition and thereby improving proton treatment planning and verification.

Over the last few decades, advances in radiotherapy (RT) technology have improved delivery of radiation therapy dramatically. Advances in treatment planning with the development of image-guided radiotherapy and in techniques such as proton therapy, allows the radiation therapist to direct high doses of radiation to the tumour. These advancements result in improved local regional control while reducing potentially damaging dosage to surrounding normal tissues. It is important for radiologists to be aware of the radiological findings from these advances in order to differentiate expected radiation-induced lung injury (RILD) from recurrence, infection, and other lung diseases. In order to understand these changes and correlate them with imaging, the radiologist should have access to the radiation therapy treatment plans., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Introduction: Advanced thymoma (stage III and IV) is difficult to detect by computed tomography (CT), yet it is important to distinguish between early (stage I and II) and advanced disease before surgery, as patients with locally advanced tumors require neoadjuvant chemotherapy to enable effective resection. This study assessed whether the amount of fluorodeoxyglucose (FDG) uptake can predict advanced thymoma and whether it can separate thymoma from thymic cancer., Methods: We retrospectively reviewed FDG positron emission tomography (PET)-CT scans of 51 consecutive newly diagnosed patients with thymic epithelial malignancy. PET-CT findings documented focal FDG activity: SUVmax, SUVmean, SUVpeak, and total body volumetric standardized uptake value (SUV) measurements. These were correlated with Masaoka-Koga staging and World Health Organization classification. Wilcoxon ranked sum tests were used to assess association between SUV and pathological stage, cancer type, and classification., Results: Among the study patients, 37 had thymoma, 12 thymic carcinoma, and 2 thymic carcinoid. Higher focal FDG uptake was seen in patients with type B3 thymoma than in those with type A, AB, B1, or B2 thymoma (p < 0.006). FDG uptake was higher in patients with thymic carcinoma or carcinoid than in patients with thymoma (p < 0.0003), with more variable associations with volumetric SUV measurements. There was no significant association observed between higher focal FDG uptake and advanced-stage disease in thymoma patients (p > 0.09), although greater FDG-avid tumor volume was significantly associated with advanced disease (p < 0.03)., Conclusions: Focal FDG uptake cannot predict advanced thymoma but is helpful in distinguishing thymoma from thymic carcinoma, or the more aggressive thymoma, type B3.

Rationale and Objectives: The aim of this study was to determine an optimum standardized uptake value (SUV) threshold for identifying regional nodal metastasis on 18F-fluorodeoxyglucose (FDG) positron emission tomographic (PET)/computed tomographic (CT) studies of patients with inflammatory breast cancer., Materials and Methods: A database search was performed of patients newly diagnosed with inflammatory breast cancer who underwent 18F-FDG PET/CT imaging at the time of diagnosis at a single institution between January 1, 2001, and September 30, 2009. Three radiologists blinded to the histopathology of the regional lymph nodes retrospectively analyzed all 18F-FDG PET/CT images by measuring the maximum SUV (SUVmax) in visually abnormal nodes. The accuracy of 18F-FDG PET/CT image interpretation was correlated with histopathology when available. Receiver-operating characteristic curve analysis was performed to assess the diagnostic performance of PET/CT imaging. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated using three different SUV cutoff values (2.0, 2.5, and 3.0)., Results: A total of 888 regional nodal basins, including bilateral axillary, infraclavicular, internal mammary, and supraclavicular lymph nodes, were evaluated in 111 patients (mean age, 56 years). Of the 888 nodal basins, 625 (70%) were negative and 263 (30%) were positive for metastasis. Malignant lymph nodes had significantly higher SUVmax than benign lymph nodes (P < .0001). An SUVmax of 2.0 showed the highest overall sensitivity (89%) and specificity (99%) for the diagnosis of malignant disease., Conclusions: SUVmax of regional lymph nodes on 18F-FDG PET/CT imaging may help differentiate benign and malignant lymph nodes in patients with inflammatory breast cancer. An SUV cutoff of 2 provided the best accuracy in identifying regional nodal metastasis in this patient population., (Copyright © 2012 AUR. Published by Elsevier Inc. All rights reserved.)

Unlabelled: We recently developed the radiotracer 4-[(3-iodophenyl)amino]-7-(2-[2-{2-(2-[2-{2-((18)F-fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide) ((18)F-PEG(6)-IPQA) for noninvasive detection of active mutant epidermal growth factor receptor kinase-expressing non-small cell lung cancer xenografts in rodents. In this study, we determined the pharmacokinetics, biodistribution, metabolism, and radiation dosimetry of (18)F-PEG(6)-IPQA in nonhuman primates., Methods: Six rhesus macaques were injected intravenously with 141 ± 59.2 MBq of (18)F-PEG(6)-IPQA, and dynamic PET/CT images covering the thoracoabdominal area were acquired for 30 min, followed by whole-body static images at 60, 90, 120, and 180 min. Blood samples were obtained from each animal at several time points after radiotracer administration. Radiolabeled metabolites in blood and urine were analyzed using high-performance liquid chromatography. The (18)F-PEG(6)-IPQA pharmacokinetic and radiation dosimetry estimates were determined using volume-of-interest analysis of PET/CT image datasets and blood and urine time-activity data., Results: (18)F-PEG(6)-IPQA exhibited rapid redistribution and was excreted via the hepatobiliary and urinary systems. (18)F-PEG(6) was the major radioactive metabolite. The critical organ was the gallbladder, with an average radiation-absorbed dose of 0.394 mSv/MBq. The other key organs with high radiation doses were the kidneys (0.0830 mSv/MBq), upper large intestine wall (0.0267 mSv/MBq), small intestine (0.0816 mSv/MBq), and liver (0.0429 mSv/MBq). Lung tissue exhibited low uptake of (18)F-PEG(6)-IPQA due to the low affinity of this radiotracer to wild-type epidermal growth factor receptor kinase. The effective dose was 0.0165 mSv/MBq. No evidence of acute cardiotoxicity or of acute or delayed systemic toxicity was observed. On the basis of our estimates, diagnostic dosages of (18)F-PEG(6)-IPQA up to 128 MBq (3.47 mCi) per injection should be safe for administration in the initial cohort of human patients in phase I clinical PET studies., Conclusion: The whole-body and individual organ radiation dosimetry characteristics and pharmacologic safety of diagnostic dosages of (18)F-PEG(6)-IPQA in nonhuman primates indicate that this radiotracer should be acceptable for PET/CT studies in human patients.

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18)F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18)F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18)F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18)F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.

Purpose: Four-dimensional computed tomography (4D-CT) is commonly used to account for respiratory motion of target volumes in radiotherapy to the thorax. From the 4D-CT acquisition, a maximum-intensity projection (MIP) image set can be created and used to help define the tumor motion envelope or the internal gross tumor volume (iGTV). The purpose of this study was to quantify the differences in automatically contoured target volumes for usage in the delivery of stereotactic body radiation therapy using MIP data sets generated from one of the four methods: (1) 4D-CT phase-binned (PB) based on retrospective phase calculations, (2) 4D-CT phase-corrected phase-binned (PC-PB) based on motion extrema, (3) 4D-CT amplitude-binned (AB), and (4) cine CT built from all available images., Methods: MIP image data sets using each of the four methods were generated for a cohort of 28 patients who had prior thoracic 4D-CT scans that exhibited lung tumor motion of at least 1 cm. Each MIP image set was automatically contoured on commercial radiation treatment planning system. Margins were added to the iGTV to observe differences in the final simulated planning target volumes (PTVs)., Results: For all patients, the iGTV measured on the MIP generated from the entire cine CT data set (iGTVcine) was the largest. Expressed as a percentage of iGTVcine, 4D-CT iGTV (all sorting methods) ranged from 83.8% to 99.1%, representing differences in the absolute volume ranging from 0.02 to 4.20 cm3; the largest average and range of 4D-CT iGTV measurements was from the PC-PB data set. Expressed as a percentage of PTVcine (expansions applied to iGTVeine), the 4D-CT PTV ranged from 87.6% to 99.6%, representing differences in the absolute volume ranging from 0.08 to 7.42 cm3. Regions of the measured respiratory waveform corresponding to a rapid change of phase or amplitude showed an increased susceptibility to the selection of identical images for adjacent bins. Duplicate image selection was most common in the AB implementation, followed by the PC-PB method. The authors also found that the image associated with the minimum amplitude measurement did not always correlate with the image that showed maximum tumor motion extent., Conclusions: The authors identified cases in which the MIP generated from a 4D-CT sorting process under-represented the iGTV by more than 10% or up to 4.2 cm3 when compared to the iGTVcine. They suggest utilization of a MIP generated from the full cine CT data set to ensure maximum inclusive tumor extent.

Average CT (ACT) and PET have a similar temporal resolution and it has been shown to improve registration of the CT and PET data for PET/CT imaging of the thorax. The purpose of this study was to quantify the effect of ACT attenuation correction on PET for gross tumor volume (GTV) delineation with standardized uptake value (SUV) for liver and esophageal lesions. Our study included 48 colorectal cancer patients with metastasis in the liver and 52 esophageal cancer patients. These patients underwent a routine PET/CT scan followed by a cine CT scan of the thoracic region for ACT. Differences between the two PET data sets (PET HCT and PET ACT ) corrected with the helical CT (HCT) and ACT were quantified by analyzing image alignment, maximum SUV (SUV max ), and GTV. The 67% of the colorectal and 73% of the esophageal studies demonstrated misregistration between the PET HCT and HCT data. ACT was effective in removing misregistration artifacts in 65% of the misregisted colorectal and in 76% of the misregisted esophageal cancer patients. Misregistration between the CT and PET data affected GTVs due to the change in SUV max with ACT. A change of SUV max greater than 20% between PET HCT and PET ACT was found in 15% of the colorectal and 17% of the esophageal cases. Our results demonstrated a more pronounced effect of misregistration for the smaller lesions (< 5 cm 3 ) near the diaphragm (< 5 cm). ACT was effective in improving registration between the CT and PET data in PET/CT for the colorectal and esophageal cancer patients.

Combined positron emission tomography and computed tomography (PET/CT) has proven clinical utility, particularly in the diagnosis, staging, and management of cancer. The use of PET/CT has grown substantially in the past few years, with an increasing number of hospitals and imaging centers installing PET/CT systems each year. The combination of 2 procedures, which each imparting a radiation dose and hence the potential for deleterious health effects, creates unique radiation safety issues. This article addresses the radiation safety issues posed by PET/CT with regard to the protection and safety of PET/CT personnel, the public, and adult and pediatric patients.

Adoptive transfer of antigen-specific cytotoxic T lymphocytes (CTLs) has been successfully used to treat patients with different types of cancer. However, the long-term spatial-temporal dynamics of the distribution of systemically infused CTLs remains largely unknown. Noninvasive imaging of adoptively transferred CTLs using molecular-genetic reporter imaging with positron emission tomography and computed tomography (PET-CT) represents an innovative approach to understanding the long-term migratory patterns and therapeutic potential of adoptively transferred T cells. Here we report the application of repetitive PET-CT imaging with [18F]fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil (18F-FEAU) in two nonhuman primates demonstrating that autologous polyclonal macaque T lymphocytes activated and transduced with a retroviral vector encoding for the sr39 mutant herpes simplex virus 1 thymidine kinase (sr39HSV1-tk) reporter gene can be detected after intravenous infusion in discrete lymphoid organs and in sites of inflammation. This study represents a proof of principle and supports the application of 18F-FEAU PET-CT imaging for monitoring the distribution of intravenously administered sr39HSV1-tk gene-transduced CTLs in humans.

Introduction: Since their introduction in 2001, PET/CT systems have gained wide acceptance primarily due to their inherent ability to combine functional and structural information about the underlying disease state of the patient in a single imaging session. Their significance has also been documented with regard to their short imaging times, which minimize patient anxiety and image blurring due to patient motion. In the past seven years, PET/CT systems have replaced dedicated PET systems as the imaging modality of choice for diagnostic evaluation of oncology patients., Objectives: The purpose of this article is to review the evolution of PET/CT systems and document their current status., Discussion: Recent improvements in instrumentation are highlighted together with some outstanding issues that arise for specific PET/CT applications. These are followed by a description of some of the more common clinical applications of PET/CT imaging such as staging malignant disease, treatment planning, and monitoring therapy response. Finally, the future developments of PET/CT systems with regard to sensitivity, resolution, and new radiopharmaceuticals are discussed. The article concludes by presenting some issues concerning the next stage in the future of PET imaging, namely PET/MRI.

Unlabelled: Our objective was to retrospectively evaluate 18F-FDG PET/CT in the initial staging of inflammatory breast cancer (IBC)., Methods: The institutional review board waived informed consent and approved this study, which was compliant with the Health Insurance Portability and Accountability Act. The cases of 41 women with a mean age of 50 y (range, 25-71 y) and newly diagnosed IBC who underwent 18F-FDG PET/CT at diagnosis were retrospectively reviewed. All PET/CT images were analyzed visually and semiquantitatively by 2 physicians. The maximum standardized uptake value in the primary breast, regional nodes (axillary, subpectoral, supraclavicular, internal mammary), and extranodal regions was documented. The accuracy of PET/CT image interpretation was assessed by histopathologic analysis, if available; concurrent or subsequent imaging findings (contrast-enhanced CT, contrast-enhanced MRI, sonography, or PET/CT follow-up); or clinical follow-up., Results: All patients presented with unilateral IBC. PET/CT showed hypermetabolic uptake in the skin in all patients, in the affected breast in 40 (98%), in the ipsilateral axillary nodes in 37 (90%), and in the ipsilateral subpectoral nodes in 18 (44%). Twenty patients (49%) were found to have distant metastases at staging, 7 (17%) of whom were not known to have metastases before undergoing PET/CT. Disease sites included bone, liver, contralateral axilla, lung, chest wall, pelvis, and the subpectoral, supraclavicular, internal mammary, mediastinal, and abdominal nodes., Conclusion: PET/CT should be considered in the initial staging of IBC, as the technique provided valuable information on locoregional and distant disease in this preliminary retrospective study.

PET/CT is an effective tool for the diagnosis, staging and restaging of cancer patients. It combines the complementary information of functional PET images and anatomical CT images in one imaging session. Conventional stand-alone PET has been replaced by PET/CT for improved patient comfort, patient throughput, and most importantly the proven clinical outcome of PET/CT over that of PET and that of separate PET and CT. There are over two thousand PET/CT scanners installed worldwide since 2001. Oncology is the main application for PET/CT. Fluorine-18 deoxyglucose is the choice of radiopharmaceutical in PET for imaging the glucose uptake in tissues, correlated with an increased rate of glycolysis in many tumor cells. New molecular targeted agents are being developed to improve the accuracy of targeting different disease states and assessing therapeutic response. Over 50% of cancer patients receive radiation therapy (RT) in the course of their disease treatment. Clinical data have demonstrated that the information provided by PET/CT often changes patient management of the patient and/or modifies the RT plan from conventional CT simulation. The application of PET/CT in RT is growing and will become increasingly important. Continuing improvement of PET/CT instrumentation will also make it easier for radiation oncologists to integrate PET/CT in RT. The purpose of this article is to provide a review of the current PET/CT technology, to project the future development of PET and CT for PET/CT, and to discuss some issues in adopting PET/CT in RT and potential improvements in PET/CT simulation of the thorax in radiation therapy.

Purpose: Patient respiratory motion can cause image artifacts in positron emission tomography (PET) from PET/computed tomography (CT) and change the quantification of PET for thoracic patients. In this study, respiration-averaged CT (ACT) was used to remove the artifacts, and the changes in standardized uptake value (SUV) and gross tumor volume (GTV) were quantified., Methods and Materials: We incorporated the ACT acquisition in a PET/CT session for 216 lung patients, generating two PET/CT data sets for each patient. The first data set (PET(HCT)/HCT) contained the clinical PET/CT in which PET was attenuation corrected with a helical CT (HCT). The second data set (PET(ACT)/ACT) contained the PET/CT in which PET was corrected with ACT. We quantified the differences between the two datasets in image alignment, maximum SUV (SUV(max)), and GTV contours., Results: Of the patients, 68% demonstrated respiratory artifacts in the PET(HCT), and for all patients the artifact was removed or reduced in the corresponding PET(ACT). The impact of respiration artifact was the worst for lesions less than 50 cm(3) and located below the dome of the diaphragm. For lesions in this group, the mean SUV(max) difference, GTV volume change, shift in GTV centroid location, and concordance index were 21%, 154%, 2.4 mm, and 0.61, respectively., Conclusion: This study benchmarked the differences between the PET data with and without artifacts. It is important to pay attention to the potential existence of these artifacts during GTV contouring, as such artifacts may increase the uncertainties in the lesion volume and the centroid location.

Purpose: Clevudine (L: -FMAU) an un-natural analogue of thymidine, is in clinical trials for the treatment of hepatitis B virus (HBV). L: -FMAU is phosphorylated by cellular kinases such as thymidine kinase 1 and deoxycytidine kinase, and its triphosphate form inhibits HBV deoxyribonucleic acid synthesis. Thus, L: -FMAU, radiolabeled with an appropriate isotope, may be useful for positron emission tomography (PET) imaging of tumor proliferation. We evaluated [18F]-L-FMAU as a PET imaging agent in tumor-bearing mice and compared the results with those of two other radiotracers, [18F]-d-FMAU and [18F]-FLT., Methods: Subcutaneous xenografts of the human lung cancer cell lines H441 and H3255 were established in mice. A micro-PET scanner was used to obtain images of the tumor-bearing animals with [18F]-L-FMAU, [18F]-D-FMAU, and [18F]-FLT., Results: At 2 h postinjection, the tumor uptake (% ID/g) of 18F]-L: -FMAU, 18F]-D: -FMAU, and [18F]-FLT in the faster-growing H441 cells was 3.13 +/- 1.11, 7.74 +/- 1.39, and 5.10 +/- 1.45, respectively. The corresponding values for the slower-growing H3255 cells were 1.38 +/- 0.81, 4.49 +/- 1.08, and 0.57 +/- 0.33. Tumor/muscle ratios of accumulation for [18F]-L: -FMAU, [18F]-D: -FMAU, and [18F]-FLT in H441 cells were 4.15 +/- 1.82, 3.37 +/- 1.19, and 12.94 +/- 4.38, respectively, and the corresponding values in H3255 cells were 1.62 +/- 0.50, 1.96 +/- 0.74, and 1.50 +/- 0.90., Conclusions: [18F]-L: -FMAU may be a useful agent for imaging tumor proliferation in fast-growing human lung cancers by PET.

Anatomy-based positron emission tomography (PET) image enhancement techniques have been shown to have the potential for improving PET image quality. However, these techniques assume an accurate alignment between the anatomical and the functional images, which is not always valid when imaging the chest due to respiratory motion. In this article, we present a joint model of both motion and anatomical information by integrating a motion-incorporated PET imaging system model with an anatomy-based maximum a posteriori image reconstruction algorithm. The mismatched anatomical information due to motion can thus be effectively utilized through this joint model. A computer simulation and a phantom study were conducted to assess the efficacy of the joint model, whereby motion and anatomical information were either modeled separately or combined. The reconstructed images in each case were compared to corresponding reference images obtained using a quadratic image prior based maximum a posteriori reconstruction algorithm for quantitative accuracy. Results of these studies indicated that while modeling anatomical information or motion alone improved the PET image quantitation accuracy, a larger improvement in accuracy was achieved when using the joint model. In the computer simulation study and using similar image noise levels, the improvement in quantitation accuracy compared to the reference images was 5.3% and 19.8% when using anatomical or motion information alone, respectively, and 35.5% when using the joint model. In the phantom study, these results were 5.6%, 5.8%, and 19.8%, respectively. These results suggest that motion compensation is important in order to effectively utilize anatomical information in chest imaging using PET. The joint motion-anatomy model presented in this paper provides a promising solution to this problem.