Investigation of Image Reconstruction Parameters of the Mediso nanoScan PC Small-Animal PET/CT Scanner for Two Different Positron Emitters Under NEMA NU 4-2008 Standards

Purpose

The Tera-Tomo 3D image reconstruction algorithm (a version of OSEM), provided with the Mediso nanoScan® PC (PET8/2) small-animal positron emission tomograph (PET)/x-ray computed tomography (CT) scanner, has various parameter options such as total level of regularization, subsets, and iterations. Also, the acquisition time in PET plays an important role. This study aims to assess the performance of this new small-animal PET/CT scanner for different acquisition times and reconstruction parameters, for 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) and Ga-68, under the NEMA NU 4-2008 standards.

Procedures

Various image quality metrics were calculated for different realizations of [¹⁸F]FDG and Ga-68 filled image quality (IQ) phantoms.

Results

[¹⁸F]FDG imaging produced improved images over Ga-68. The best compromise for the optimization of all image quality factors is achieved for at least 30 min acquisition and image reconstruction with 52 iteration updates combined with a high regularization level.

Conclusion

A high regularization level at 52 iteration updates and 30 min acquisition time were found to optimize most of the figures of merit investigated.

     

Repeatability of Radiomic Features in Non-Small-Cell Lung Cancer [<Superscript>18</Superscript>F]FDG-PET/CT Studies: Impact of Reconstruction and Delineation

Purpose

To assess (1) the repeatability and (2) the impact of reconstruction methods and delineation on the repeatability of 105 radiomic features in non-small-cell lung cancer (NSCLC) 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomorgraphy/computed tomography (PET/CT) studies.

Procedures

Eleven NSCLC patients received two baseline whole-body PET/CT scans. Each scan was reconstructed twice, once using the point spread function (PSF) and once complying with the European Association for Nuclear Medicine (EANM) guidelines for tumor PET imaging. Volumes of interest (n?=?19) were delineated twice, once on PET and once on CT images.

Results

Sixty-three features showed an intraclass correlation coefficient?≥?0.90 independent of delineation or reconstruction. More features were sensitive to a change in delineation than to a change in reconstruction (25 and 3 features, respectively).

Conclusions

The majority of features in NSCLC [¹⁸F]FDG-PET/CT studies show a high level of repeatability that is similar or better compared to simple standardized uptake value measures.

     

<Emphasis Type="Italic">In Vitro</Emphasis> and <Emphasis Type="Italic">In Vivo</Emphasis> Comparison of Selected Ga-68 and Zr-89 Labelled Siderophores

Purpose

Some [⁶⁸Ga]siderophores show promise in specific and sensitive imaging of infection. Here, we compare the in vitro and in vivo behaviour of selected Ga-68 and Zr-89 labelled siderophores.

Procedures

Radiolabelling was performed in HEPES or sodium acetate buffer systems. Radiochemical purity of labelled siderophores was determined using chromatography. Partition coefficients, in vitro stability and protein binding affinities were determined. Ex vivo biodistribution and animal imaging was studied in mice.

Results

Certain differences among studied siderophores were observed in labelling efficiency. Protein binding and stability tests showed highest stabilities and lowest protein binding affinities for Ga-68 and [⁸⁹Zr]triacetylfusarinine C (TAFC). All studied Ga-68 and [⁸⁹Zr]siderophores exhibited a similar biodistribution and pharmacokinetics in mice with the exception of [⁸⁹Zr]ferrioxamine E (FOXE).

Conclusions

Zr-89 and [⁶⁸Ga]siderophores showed analogous in vitro and in vivo behaviour. Tested [⁸⁹Zr]siderophores could be applied for longitudinal positron emission tomography (PET) studies of fungal infections and especially TAFC for the development of novel bioconjugates.

     

Applying Amide Proton Transfer MR Imaging to Hybrid Brain PET/MR: Concordance with Gadolinium Enhancement and Added Value to [<Superscript>18</Superscript>F]FDG PET

Purpose

The purpose of this study is to evaluate the diagnostic concordance and metric correlations of amide proton transfer (APT) imaging with gadolinium-enhanced magnetic resonance imaging (MRI) and 2-deoxy-2-[¹⁸F-]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography (PET), using hybrid brain PET/MRI.

Procedures

Twenty-one subjects underwent brain gadolinium-enhanced [¹⁸F]FDG PET/MRI prospectively. Imaging accuracy was compared between unenhanced MRI, MRI with enhancement, APT-weighted (APTW) images, and PET based on six diagnostic criteria. Among tumors, the McNemar test was further used for concordance assessment between gadolinium-enhanced imaging, APT imaging, and [¹⁸F]FDG PET. As well, the relation of metrics between APT imaging and PET was analyzed by the Pearson correlation analysis.

Results

APT imaging and gadolinium-enhanced MRI showed superior and similar diagnostic accuracy. APTW signal intensity and gadolinium enhancement were concordant in 19 tumors (100 %), while high [¹⁸F]FDG avidity was shown in only 12 (63.2 %). For the metrics from APT imaging and PET, there was significant correlation for 13 hypermetabolic tumors (P < 0.05) and no correlation for the remaining six [¹⁸F]FDG-avid tumors.

Conclusions

APT imaging can be used to increase diagnostic accuracy with no need to administer gadolinium chelates. APT imaging may provide an added value to [¹⁸F]FDG PET in the evaluation of tumor metabolic activity during brain PET/MR studies.

     

Improvements in PET Image Quality in Time of Flight (TOF) Simultaneous PET/MRI

Purpose

An integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanner with time of flight (TOF) technology is now available for clinical use. The aim of this study is to evaluate the potential of TOF PET in PET/MRI to reduce artifacts in PET images when compared to non-TOF PET/MRI, TOF PET/X-ray computed tomography (CT), and non-TOF PET/CT.

Procedures

All patients underwent a single 2-deoxy-2-[¹⁸F]fluoro-d-glucose ([¹⁸F]FDG) injection, followed first by PET/CT, and subsequently by PET/MRI. PET/CT exams were requested as standard-of-care for oncological indications. Using the PET acquisitions datasets, 4 series of images (TOF PET/CT, non-TOF PET/CT, TOF PET/MRI, and non-TOF PET/MRI) were reconstructed. These image series were visually evaluated for: (1) dental metal artifacts, (2) breathing artifacts, and (3) pelvic artifacts due to scatter correction errors from high bladder [¹⁸F]FDG concentration. PET image quality was assessed by a 3-point scale (1—clinically significant artifact, 2—non clinically significant artifact, and 3—no artifact).

Results

Twenty-five patients (mean?±?SD age: 56?±?13 years old; female: 10, male: 15) were enrolled. TOF PET/MRI, non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT scores 2.8, 2.5, 2.4, and 2.3, respectively for the presence of dental artifacts, 2.8, 2.5, 2.2, and 1.9, respectively, for the presence of breathing artifacts, and 2.7, 1.7, 2.0, and 1.3, respectively, for the presence of pelvic artifacts TOF PET/MRI images showed the highest image quality scores among the 4 datasets of PET images.

Conclusion

The superior timing resolution and resulting TOF capability of the new PET/MRI scanner improved PET image quality in this cohort by reducing artifacts compared to non-TOF PET/MRI, TOF PET/CT, and non-TOF PET/CT.

     

Noise-Induced Variability of Immuno-PET with Zirconium-89-Labeled Antibodies: an Analysis Based on Count-Reduced Clinical Images

Purpose

Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.

Procedures

Data were acquired from three previously reported clinical studies with [⁸⁹Zr]antiCD20 (74 MBq, n?=?7), [⁸⁹Zr]antiEGFR (37 MBq, n?=?7), and [⁸⁹Zr]antiCD44 (37 MBq, n?=?13), with imaging obtained 1 to 6 days post injection (D0–D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq_74inj).Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.

Results

The RC for the combined manually delineated organs for [⁸⁹Zr] antiCD20 (37 MBq_74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq_74inj at D6. For tumor, the RC was up to 42 % for [⁸⁹Zr]antiCD20 (37 MBq_74inj). For [⁸⁹Zr]antiCD20, (18 MBq_74inj), [⁸⁹Zr]antiEGFR (18 MBq_37inj), and [⁸⁹Zr]antiCD44 (18 MBq_37inj), measurement variability was independent of the investigated antibody.

Conclusions

Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.

     

Incremental Value of Integrated FDG-PET/CT in Evaluating Indeterminate Solitary Pulmonary Nodule for Malignancy

Objectives

The objective of this study was to evaluate the increased diagnostic benefit of integrated positron emission tomography/computed tomography (PET/CT) interpretation in evaluating solitary pulmonary nodules for malignancy.

Methods

One hundred seventeen patients (67 men and 50 women; mean age ± SD, 61.7?±?13.6 years, range, 31–86 years) with indeterminate solitary pulmonary nodules and no previous history of malignancy were analyzed. PET/CT was performed with an integrated PET/CT scanner (Siemens Biograph BGO duo) 1 h after an intravenous injection of 370 MBq (10 mCi) ¹⁸F-fluorodeoxyglucose. Patients fasted for 6 h before imaging. PET was interpreted alone or combined with CT and was graded according to a five-point scale. A malignant diagnosis was based on histological findings or a clinical and radiological follow-up after at least 24 months. The diagnostic performances of PET alone and integrated PET/CT interpretation were evaluated using discriminant analysis.

Results

PET alone correctly classified 85% of nodules and integrated PET/CT interpretation increased the correct classification to 89%, with similar sensitivity and specificity of 88% and 89%, respectively. False-positive PET results mainly resulted from granulomatous disorders. Four (50%) of the eight cases deemed indeterminate on PET alone were resolved with combined PET/CT interpretation.

Conclusions

Although the benefit attributable to the CT component was limited when integrated PET/CT was used, PET and CT acted synergistically to significantly increase the diagnostic veracity for PET-indeterminate nodules.

     

The Effect of Defective PET Detectors in Clinical Simultaneous [<Superscript>18</Superscript>F]FDG Time-of-Flight PET/MR Imaging

Purpose

The purpose of this study was to evaluate the effect of defective positron emission tomography (PET) detectors on clinical PET image quality in simultaneous PET/magnetic resonance imaging (MRI) for both time-of-flight (TOF) and non-TOF reconstructed images.

Procedures

A total of six patients with various malignant tumors were included and underwent a 2-deoxy-2-[¹⁸F]fluoro-d-glucose PET scan in a fully functional simultaneous TOF PET/MRI. TOF and non-TOF PET images were reconstructed before and after simulating defective detector units. All images were clinically assessed and scored. In addition, a quantitative assessment was performed. Differences were ascertained and compared using the Wilcoxon matched pairs signed-rank test.

Results

Without TOF, the image artifacts introduced by one defective detector unit already started to degrade the overall image quality. It reduced the confidence and could lead to a change in diagnosis. Simulating three or five defective detector units resulted in more artifacts and further reduced overall image quality and confidence. By including TOF information, the effects were mitigated: Images reconstructed with one defective detector unit had similar scores as the ones without defective units. The average absolute percentage error for one, three, and five defective detector units were respectively 8, 20, and 37 % for the non-TOF cases and only 5, 11, and 19 % for the TOF cases.

Conclusion

Our study indicates that PET image artifacts due to (simulated) defective detectors are significantly mitigated with the integration of TOF information in simultaneous PET/MR. One defective detector unit introduces, on average, a 5 % absolute percentage error. However, in TOF imaging, even in cases with one or three defective units for head and neck imaging and one defective unit for chest and abdominal imaging, overall image quality, artifact scoring, and reader confidence are not significantly degraded.

     

Consistent reconstruction of 4D fetal heart ultrasound images to cope with fetal motion

Purpose

4D ultrasound imaging of the fetal heart relies on reconstructions from B-mode images. In the presence of fetal motion, current approaches suffer from artifacts, which are unrecoverable for single sweeps.

Methods

We propose to use many sweeps and exploit the resulting redundancy to automatically recover from motion by reconstructing a 4D image which is consistent in phase, space, and time. An interactive visualization framework to view animated ultrasound slices from 4D reconstructions on arbitrary planes was developed using a magnetically tracked mock probe.

Results

We first quantified the performance of 10 4D reconstruction formulations on simulated data. Reconstructions of 14 in vivo sequences by a baseline, the current state-of-the-art, and the proposed approach were then visually ranked with respect to temporal quality on orthogonal views. Rankings from 5 observers showed that the proposed 4D reconstruction approach significantly improves temporal image quality in comparison with the baseline. The 4D reconstructions of the baseline and the proposed methods were then inspected interactively for accessibility to clinically important views and rated for their clinical usefulness by an ultrasound specialist in obstetrics and gynecology. The reconstructions by the proposed method were rated as ‘very useful’ in 71% and were statistically significantly more useful than the baseline reconstructions.

Conclusions

Multi-sweep fetal heart ultrasound acquisitions in combination with consistent 4D image reconstruction improves quality as well as clinical usefulness of the resulting 4D images in the presence of fetal motion.

     

Labrumrekonstruktion – wie ist die Evidenz?

Background

The labrum is a biomechanically important structure of the hip joint. In the event of labral loss the new technique of labral reconstruction is aimed at restoring the anatomy and function of the labrum and thus prevention of joint degeneration.

Objective

The results and evidence relating to labral reconstruction are presented.

Material and methods

The currently available studies were evaluated and the biomechanical and clinical articles on labral reconstruction are discussed.

Results

There are a large number of different indications and surgical variants of this procedure. Biomechanical and clinical studies concerning labral defects show that the situation is improved by a reconstruction.

Discussion

As a result of the small number of cases and the low quality of the publications, there is as yet a lack of clinical evidence concerning this new surgical method. The biomechanical results suggest that reconstruction of a segmental labral defect is plausible for selected cases. Initial clinical results have to be confirmed by further studies in the long term.

     

Imaging Early Fate of Cancer Stem Cells in Mouse Hindlimbs with Sodium Iodide Symporter Gene and I-124 PET

Purpose

We investigated the capacity of sodium/iodide symporter (NIS) positron emission tomography (PET) to image and quantitate early engraftment and survival of cancer stem cells (CSCs) in living mice.

Procedures

CT26 colon cancer cells and CSCs were infected with an adenovirus expressing both NIS and enhanced green fluorescent protein (EGFP). Cells were implanted into normal and ischemic hindlimbs of mice, and serial optical and I-124 PET imaging was performed. Extracted tissues underwent I-124 measurements and confocal microscopy.

Results

NIS.EGFP gene transfer increased fluorescence and I-124 uptake of CSCs and CT26 cells without adverse effects. I-124 PET clearly visualized implanted tumor cells in vivo, whereas optical imaging was suboptimal. PET revealed 1.95, 2.22, and 1.93-fold greater I-124 uptake by CSC inoculation into ischemic compared to non-ischemic limbs at 2, 15, and 24 h, respectively. CT26 cells showed similar but smaller differences. PET findings were confirmed by ex vivo measurements and confocal microscopy.

Conclusions

NIS PET can help identify microenvironment conditions that influence early survival of implanted CSCs.

     

Systems,Physics, and Instrumentation of PET/MRI for Cardiovascular Studies

Purpose of Review

In the years 2011–2014, three different whole-body PET/MRI hybrid systems from different vendors have been introduced to the market. While this rather new hybrid imaging modality is primarily used in clinical oncologic and neurologic hybrid imaging, cardiovascular applications are now gaining broader utilization. Cardiovascular hybrid imaging with PET/MRI is especially challenging because the independent data acquisition with PET and MRI is to be synchronized to breathing and cardiac motion to fully make use of the diagnostic potential inherent to this new hybrid method.

Recent Findings

New methodological developments and refinements in attenuation, truncation, and motion correction for PET/MRI further improve overall image quality and PET quantification in cardiovascular imaging applications. The rather complex hybrid imaging workflow integrating motion correction techniques is further streamlined to facilitate usability and to increase the diagnostic application spectrum.

Summary

Instrumentation and methodology over the recent years have matured to a level that PET/MRI today is a powerful addition to the palette of hybrid imaging modalities in cardiovascular applications.

     

[<Superscript>89</Superscript>Zr]Trastuzumab: Evaluation of Radiation Dosimetry,Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer

Purpose

The purpose of the present study is to evaluate safety, human radiation dosimetry, and optimal imaging time of [⁸⁹Zr]trastuzumab in patients with HER2-positive breast cancer.

Procedures

Twelve women with HER2-positive breast cancer underwent [⁸⁹Zr]trastuzumab positron emission tomography (PET)/X-ray computed tomography (CT) twice within 7 days post-injection. Biodistribution data from whole-torso PET/CT images and organ time-activity curves were created using data from all patients. Human dosimetry was calculated using OLINDA with the adult female model.

Results

High-quality images and the greatest tumor-to-nontumor contrast were achieved with images performed 5?±?1 day post-injection. Increased [⁸⁹Zr]trastuzumab uptake was seen in at least one known lesion in ten patients. The liver was the dose-limiting organ (retention of ～12 % of the injected dose and average dose of 1.54 mSv/MBq). The effective dose was 0.47 mSv/MBq. No adverse effects of [⁸⁹Zr]trastuzumab were encountered.

Conclusion

[⁸⁹Zr]trastuzumab was safe and optimally imaged at least 4 days post-injection. The liver was the dose-limiting organ.

     

The PGRMC1 Protein Level Correlates with the Binding Activity of a Sigma-2 Fluorescent Probe (SW120) in Rat Brain Cells

Purpose

We examined the progesterone receptor membrane component 1 (PGRMC1) protein expression in rat brain cells as the prerequisite step to understand the biology of PGRMC1 in the central nervous system (CNS). We also performed correlation studies between the PGRMC1 protein level and the binding activity of a sigma-2 fluorescent probe, SW120, in order to explore the possibility of using sigma-2 radiotracer of positron emission tomography (PET) to noninvasively image the CNS.

Procedures

Embryonic primary neurons, astrocytes, oligodendrocytes, and microglia cells were cultured. Immunocytochemistry, Western blot, and SW120 staining were performed in these cells.

Results

The protein expression of PGRMC1 determined by immunocytochemistry and SW120 staining is prominent in neurons and relatively low in astrocytes, oligodendrocytes, and microglia cells. The PGRMC1 expression level correlates with the binding activity of SW120 in rat brain cells.

Conclusions

The sigma-2 receptor PET radiotracer can be potentially used to noninvasively image neuron/synapse densities in the CNS.

     

Human Radiation Dosimetry of [<Superscript>18</Superscript>F]AV-1451(T807) to Detect Tau Pathology

Purpose

[¹⁸F]AV-1451 is a positron emission tomography (PET) radioligand for detecting paired helical filament tau. Our aim was to estimate the radiation dose of [¹⁸F]AV-1451 in humans.

Procedures

Whole-body PET scans were acquired for six healthy volunteers (three male, three female) for 128 min after injection of [¹⁸F]AV-1451 (268?±?31 MBq). Radiation doses were estimated using the OLINDA/EXM software.

Results

The estimated organ doses ranged from 7.81 to 81.2 μSv/MBq. The critical organ for radiation burden was the liver. Radiation doses to the reproductive and blood-forming organs were 14.15, 8.43, and 18.35 μSv/MBq for the ovaries, testes, and red marrow, respectively. The mean effective dose was 22.47?±?3.59 μSv/MBq.

Conclusions

A standard single injection of 185 MBq (5 mCi) results in an effective dose of 4.7 mSv in a healthy subject. Therefore, [¹⁸F]AV-1451 could be used in multiple PET scans of the same subject per year.

     

Cardiovascular PET/MRI: Initial Clinical Experience

Purpose of Review

The study aims to give a review of the current state of cardiovascular hybrid PET/MRI and to outline its evolution in near future.

Recent Findings

Proof of feasibility of cardiovascular hybrid PET/MRI has been provided for different cardiovascular pathologies using [¹⁸F]-fluorodeoxyglucose (FDG) as tracer; hybrid FDG PET/MRI allows in acute myocardial infarction the visualization of the area-at-risk of infarction, and initial studies show the prognostic value of PET/MRI concerning functional recovery in acute myocardial infarction. FDG PET/MRI enables the detection of inflammation in viral myocarditis; however, its clinical benefit is still unexplored. In sarcoidosis, cardiac PET/MRI provides a higher diagnostic accuracy compared to PET and MRI alone. PET/MRI shows an improved specificity concerning the differentiation between benign and malignant cardiac tumors compared to PET and MRI alone.

Summary

Cardiovascular PET/MRI is feasible, and initial studies show promising results and suggest an added value of hybrid PET/MRI over PET and MRI alone.

     

Coronary CTA for Surveillance of Cardiac Allograft Vasculopathy

Purpose of Review

The purpose of this review is to highlight recent hardware and software advances in coronary computed tomography angiography (CTA) that make it a potentially viable alternative to invasive coronary angiography for surveillance of cardiac allograft vasculopathy (CAV) in heart transplant recipients.

Recent Findings

Dual-source CT, multisegment reconstruction, and intracycle motion correction algorithms are all technologies applied during or after image acquisition that can improve image quality and diagnostic accuracy in patients with elevated heart rates, such as heart transplant recipients. CT fractional flow reserve may also add value in this clinical scenario.

Summary

Coronary CTA now has equivalent diagnostic accuracy, offers more nuanced anatomic information, is inherently safer, and could be less costly than invasive coronary angiography. For these reasons, coronary CTA may now be a viable alternative to ICA for CAV surveillance in heart transplant recipients.

     

Evaluation of PET Imaging Performance of the TSPO Radioligand [<Superscript>18</Superscript>F]DPA-714 in Mouse and Rat Models of Cancer and Inflammation

Purpose

Many radioligands have been explored for imaging the 18-kDa translocator protein (TSPO), a diagnostic and therapeutic target for inflammation and cancer. Here, we investigated the TSPO radioligand [¹⁸F]DPA-714 for positron emission tomography (PET) imaging of cancer and inflammation.

Procedures

[¹⁸F]DPA-714 PET imaging was performed in 8 mouse and rat models of breast and brain cancer and 4 mouse and rat models of muscular and bowel inflammation.

Results

[¹⁸F]DPA-714 showed different uptake levels in healthy organs and malignant tissues of mice and rats. Although high and displaceable [¹⁸F]DPA-714 binding is observed ex vivo, TSPO-positive PET imaging of peripheral lesions of cancer and inflammation in mice did not show significant lesion-to-background signal ratios. Slower [¹⁸F]DPA-714 metabolism and muscle clearance in mice compared to rats may explain the elevated background signal in peripheral organs in this species.

Conclusion

Although TSPO is an evolutionary conserved protein, inter- and intra-species differences call for further exploration of the pharmacological parameters of TSPO radioligands.

     

High Impact of <Superscript>18</Superscript>F-FDG-PET on Management and Prognostic Stratification of Newly Diagnosed Small Cell Lung Cancer

Purpose

We evaluated whether ¹⁸F-FDG-PET altered stage classification, management, and prognostic stratification of newly diagnosed small cell lung cancer (SCLC).

Procedures

We identified 46 consecutive patients undergoing staging positron emission tomography for SCLC from 1993–2008 inclusive. Updated survival data from the state Cancer Registry was available on 42 of 46 patients.

Results

PET altered stage classification in 12 of 46 (26%) patients. PET altered treatment modality in nine patients, and the target mediastinal radiation field in another three patients. Therefore, PET altered management in 12 of 46 (26%) patients. Patients with limited disease (LD) on pre-PET staging had significantly longer overall survival (OS) than those upstaged to extensive disease (ED; median 18.6 months versus 5.7 months; log-rank p?versus 5.9 months; log-rank p?=?0.037).

Conclusion

PET had a major impact on stage classification, management, and prognostic stratification of newly diagnosed SCLC.

     

The Synergistic Effect of Selumetinib/Docetaxel Combination Therapy Monitored by [<Superscript>18</Superscript> F]FDG/[<Superscript>18</Superscript> F]FLT PET and Diffusion-Weighted Magnetic Resonance Imaging in a Colorectal Tumor Xenograft Model

Purpose

Positron emission tomography (PET) and diffusion-weighted MRI (DW-MRI) were used to characterize the treatment effects of the MEK1/2 inhibitor selumetinib (AZD6244), docetaxel, and their combination in HCT116 tumor-bearing mice on the molecular level.

Procedures

Mice were treated with vehicle, selumetinib (25 mg/kg), docetaxel (15 mg/kg), or a combination of both drugs for 7 days and imaged at four time points with 2-deoxy-2-[¹⁸?F]fluoro-D-glucose ([¹⁸?F]FDG) or 3′-deoxy-3′-[¹⁸?F]fluorothymidine ([¹⁸?F]FLT) followed by DW-MRI to calculate the apparent diffusion coefficient (ADC). Data was cross-validated using the Pearson correlation coefficient (PCC) and compared to histology (IHC).

Results

Each drug led to tumor growth inhibition but their combination resulted in regression. Separate analysis of PET or ADC could not provide significant differences between groups. Only PCC combined with IHC analysis revealed the highest therapeutic impact for combination therapy.

Conclusion

Combination treatment of selumetinib/docetaxel was superior to the respective mono-therapies shown by PCC of PET and ADC in conjunction with histology.