332 results found
Heinzmann K, Schelhaas S, Wachsmuth L, et al., 2018, Thymidine metabolism as confounding factor of 3’-Deoxy-3’-[18F]Fluorothymidine uptake after therapy in a colorectal cancer model, Journal of Nuclear Medicine, Vol: 59, Pages: 1063-1069, ISSN: 1535-5667
Non-invasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer (CRC) xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Methods: Tumor bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 CRC xenografts, were treated with FOLFOX (5 fluorouracil, leucovorin and oxaliplatin) in weekly intervals. On d1, d2, d6, d9 and d13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on d1 of therapy. Results: In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3’-deoxy-3’-[18F]fluorothymidine ([18F]FLT), which was accompanied by increases in markers for proliferation (Ki67, TK1) and for activated DNA damage response (DDR; γH2AX), whereas the effect on cell death was minimal. As tracer uptake was unaltered in the HCT116 model, these changes appear to be specific for tumor response. Conclusion: We demonstrate that [18F]FLT PET can non-invasively monitor molecular alterations induced by a cancer treatment, including thymidine metabolism and DDR. The cellular or imaging changes may not, however, be directly related to therapy response as assessed by volumetric measurements.
Pardo OE, Rupniewska E, Roy R, et al., 2018, Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors, Oncotarget, Vol: 9, Pages: 27346-27362, ISSN: 1949-2553
Lung cancer is the main cancer killer in both men and women, mostly due to the rapid development of drug resistant metastatic disease. Here, we evaluate the potential involvement of SRC family kinases (SFK) in lung cancer biology and assess the possible benefits of their inhibition as a therapeutic approach. We demonstrated that various SRC family members, including LYN and LCK, normally expressed solely in hematopoietic cells and neural tissues, are overexpressed and activated in a panel of SCLC and NSCLC cell lines. This was clinically relevant as LYN and FYN are also overexpressed in lung cancer clinical specimens. Moreover, LYN overexpression correlated with decreased patient survival on univariate and multivariate analysis. Dasatinib (BMS-354825), a SRC/ABL inhibitor, effectively blocked SFK activation at nanomolar concentrations which correlated with a significant decrease in cell numbers of multiple lung cancer cell lines. This effect was matched by a decrease in DNA synthesis, but only moderate induction of apoptosis. Indeed, dasatinib as well as PP2, another SFK inhibitor, strongly induced autophagy that likely prevented apoptosis. However, inhibition of this autophagic response induced robust apoptosis and sensitised lung cancer cells to dasatinib in vitro and in vivo. Our results provide an explanation for why dasatinib failed in NSCLC clinical trials. Furthermore, our data suggest that combining SFK inhibitors with autophagy inhibitors could provide a novel therapeutic approach in this disease.
Inglese M, Grech-Sollars M, Ordidge K, et al., Association between pharmacokinetic parameters from DCE-MRI and metabolic parameters from dynamic 18F-fluoromethylcholine PET in human brain glioma, 27th International Society for Magnetic Resonance in Medicine
Inglese M, Honeyfield L, Aboagye E, et al., Comparison of the Tofts and the Shutter Speed Model for DCE-MRI in patients with Brain Glioma, 27th International Society for Magnetic Resonance in Medicine
Kramer GM, Liu Y, de Langen AJ, et al., 2018, Repeatability of quantitative18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 45, Pages: 951-961, ISSN: 1619-7070
INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. METHODS: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five18F-FLT repeatability cohorts in solid tumors.18F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. RESULTS: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all18F-FLT uptake metrics (R2 ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUVpeak(RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUVmax ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repe
Valindria V, Pawlowski N, Rajchl M, et al., 2018, Multi-modal learning from unpaired images: Application to multi-organ segmentation in CT and MRI, IEEE Winter Conference on Applications of Computer Vision, Publisher: IEEE
Convolutional neural networks have been widely used in medical image segmentation. The amount of training data strongly determines the overall performance. Most approaches are applied for a single imaging modality, e.g., brain MRI. In practice, it is often difficult to acquire sufficient training data of a certain imaging modality. The same anatomical structures, however, may be visible in different modalities such as major organs on abdominal CT and MRI. In this work, we investigate the effectiveness of learning from multiple modalities to improve the segmentation accuracy on each individual modality. We study the feasibility of using a dual-stream encoder-decoder architecture to learn modality-independent, and thus, generalisable and robust features. All of our MRI and CT data are unpaired, which means they are obtained from different subjects and not registered to each other. Experiments show that multi-modal learning can improve overall accuracy over modality-specific training. Results demonstrate that information across modalities can in particular improve performance on varying structures such as the spleen.
Hajitou A, Campbell S, Suwan K, et al., 2018, Selective inhibition of histone deacetylation in melanoma increases targeted gene delivery by a bacteriophage viral vector, Cancers, Vol: 10, ISSN: 2072-6694
The previously developed adeno-associated virus/phage (AAVP) vector, a hybrid between M13 bacteriophage (phage) viruses that infect bacteria only and human Adeno-Associated Virus (AAV), is a promising tool in targeted gene therapy against cancer. AAVP can be administered systemically and made tissue specific through the use of ligand-directed targeting. Cancer cells and tumor-associated blood vessels overexpress the αν integrin receptors, which are involved in tumor angiogenesis and tumor invasion. AAVP is targeted to these integrins via a double cyclic RGD4C ligand displayed on the phage capsid. Nevertheless, there remain significant host-defense hurdles to the use of AAVP in targeted gene delivery and subsequently in gene therapy. We previously reported that histone deacetylation in cancer constitutes a barrier to AAVP. Herein, to improve AAVP-mediated gene delivery to cancer cells, we combined the vector with selective adjuvant chemicals that inhibit specific histone deacetylases (HDAC). We examined the effects of the HDAC inhibitor C1A that mainly targets HDAC6 and compared this to sodium butyrate, a pan-HDAC inhibitor with broad spectrum HDAC inhibition. We tested the effects on melanoma, known for HDAC6 up-regulation, and compared this side by side with a normal human kidney HEK293 cell line. Varying concentrations were tested to determine cytotoxic levels as well as effects on AAVP gene delivery. We report that the HDAC inhibitor C1A increased AAVP-mediated transgene expression by up to ~9-fold. These findings indicate that selective HDAC inhibition is a promising adjuvant treatment for increasing the therapeutic value of AAVP.
Lledos M, Mirabello V, Sarpaki S, et al., 2018, Synthesis, radiolabelling and in vitro imaging of multifunctional nanoceramics, ChemNanoMat, Vol: 4, Pages: 361-372, ISSN: 2199-692X
Molecular imaging has become a powerful technique in preclinical and clinical research aiming towards the diagnosis of many diseases. In this work, we address the synthetic challenges in achieving lab‐scale, batch‐to‐batch reproducible copper‐64‐ and gallium‐68‐radiolabelled metal nanoparticles (MNPs) for cellular imaging purposes. Composite NPs incorporating magnetic iron oxide cores with luminescent quantum dots were simultaneously encapsulated within a thin silica shell, yielding water‐dispersible, biocompatible and luminescent NPs. Scalable surface modification protocols to attach the radioisotopes 64Cu (t1/2=12.7 h) and 68Ga (t1/2=68 min) in high yields are reported, and are compatible with the time frame of radiolabelling. Confocal and fluorescence lifetime imaging studies confirm the uptake of the encapsulated imaging agents and their cytoplasmic localisation in prostate cancer (PC‐3) cells. Cellular viability assays show that the biocompatibility of the system is improved when the fluorophores are encapsulated within a silica shell. The functional and biocompatible SiO2 matrix represents an ideal platform for the incorporation of 64Cu and 68Ga radioisotopes with high radiolabelling incorporation.
Schelhaas S, Heinzmann K, Honess DJ, et al., 2018, 3'-Deoxy-3'-[(18)F]Fluorothymidine uptake is related to thymidine phosphorylase expression in various experimental tumor models, Molecular Imaging and Biology, Vol: 20, Pages: 194-199, ISSN: 1536-1632
PURPOSE: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models. PROCEDURES: Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [(18)F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations. RESULTS: Expression of TP correlated positively with [(18)F]FLT SUVmax (ρ = 0.549, P < 0.05). Furthermore, tumors with high TP levels possessed lower levels of thymidine (ρ = - 0.939, P < 0.001). CONCLUSIONS: In a broad range of tumors, [(18)F]FLT uptake as measured by PET is substantially influenced by TP expression and tumor thymidine concentrations. These data strengthen the role of TP as factor confounding [(18)F]FLT uptake.
Ali S, Patel H, Periyasamy M, et al., 2018, ICEC0942, an orally bioavailable selective inhibitor of CDK7 for cancer treatment, Molecular Cancer Therapeutics, ISSN: 1535-7163
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942. It selectively inhibits CDK7, with an IC50 of 40nM; IC50 values for CDK1, CDK2, CDK5 and CDK9 were 45-, 15-, 230- and 30-fold higher. In vitro studies show that a wide range of cancer types are sensitive to CDK7 inhibition with GI50 values ranging between 0.2-0.3 µM. In xenografts of both breast and colorectal cancers, the drug has substantial anti-tumor effects. Additionally, combination therapy with tamoxifen showed complete growth arrest of ER-positive tumor xenografts. Our findings reveal that CDK7 inhibition provides a new approach, especially for ER-positive breast cancer and identify ICEC0942 as a prototype drug with potential utility as a single agent or in combination with hormone therapies for breast cancer. ICEC0942 may also be effective in other cancers that display characteristics of transcription factor addiction, such as acute leukaemia, and small-cell lung cancer.
Khan RU, Zhang X, Kumar R, et al., 2018, Evaluating the Performance of ResNet Model Based on Image Recognition, International Conference on Computing and Artificial Intelligence (ICCAI), Publisher: ASSOC COMPUTING MACHINERY, Pages: 86-90
Aboagye EO, James GC, Gao J, et al., 2018, Probabilistic Time Context Framework for Big Data Collaborative Recommendation, International Conference on Computing and Artificial Intelligence (ICCAI), Publisher: ASSOC COMPUTING MACHINERY, Pages: 118-121
Heinzmann K, Honess DJ, Lewis DY, et al., 2017, The relationship between endogenous thymidine concentrations and [F-18]FLT uptake in a range of preclinical tumour models (vol 6, 63, 2016), EJNMMI Research, Vol: 7, ISSN: 2191-219X
Cowell S, Carroll L, Lavdas I, et al., 2017, Towards an MMP-2-activated molecular agent for cancer imaging, Dalton Transactions, Vol: 47, Pages: 1530-1534, ISSN: 1477-9234
Matrix metalloproteinases (MMPs) have been identified as biomarkers for cancer, offering prognostic potential; however, non-invasive detection protocols are currently lacking. Herein, we describe the synthesis of a DOTA-containing peptide sequence that can be radiolabelled easily with 68Gallium or can be incorporated with gadolinium for possible MRI applications with clear selectivity for MMP-2 over other members of the MMP family, giving MMP-2 selective cleavage of the labelled peptides.
Leow CH, Marta B, Stanziola A, et al., 2017, Multi-Frame Rate Plane Wave Contrast-Enhance Ultrasound Imaging for Tumour Vasculature Imaging and Perfusion Quantification, IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, ISSN: 1948-5719
A multi-frame rate plane wave imaging strategy is developed to simultaneously image tumor vasculature and quantify tumor perfusion. Customised imaging sequences interleaving a short but high frame rate (HFR) plane wave imaging sequence with a long but low frame rate imaging (LFR) sequence were implemented using a programmable ultrasound research platform. The results from a spatio-temporal coherence processing technique of ours demonstrated a significant improvement in the SNR and vasculature contrast when compared with the existing ultrafast Power Doppler (PD) using the same data. Initial perfusion quantification using LFR imaging was also demonstrated. Mean time intensity curve and some parametric measures were generated. Combining both structural and functional perfusion imaging using the multiframe rate sequences, a better evaluation of the tumour angiogenesis can be assessed.
Leow CH, Braga M, Hernandez-Gil J, et al., 2017, Multi-frame rate plane wave contrast-enhanced ultrasound imaging for tumour vascular imaging and perfusion quantification, IEEE International Ultrasonics Symposium, IUS, Publisher: IEEE, ISSN: 1948-5719
Angiogenesis and blood flow dynamics play an important role in the development of malignant tumours and their response to treatment. While contrast enhanced ultrasound (CEUS) imaging with microbubble contrast agents as a tool for imaging angiogenesis and flow dynamics has shown great potential , recent development of plane wave high frame-rate (HFR) CEUS has offered new opportunities in such applications. In this study, we demonstrate an interleaved multi-frame rate plane wave CEUS imaging to quantify perfusion and to image vascular structure with improved resolution and contrast.
Dubash SR, Merchant S, Mauri F, et al., 2017, Clinical translation of the caspase 3/7 specific PET radiotracer [F-18]ICMT-11 for measuring chemotherapy induced apoptosis in breast and lung cancer, Publisher: SPRINGER, Pages: S378-S379, ISSN: 1619-7070
Saleem A, Searle GE, Kenny LM, et al., 2017, Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer (vol 5, 30, 2015), EJNMMI RESEARCH, Vol: 7, ISSN: 2191-219X
Complex molecular and metabolic phenotypes depict cancers as a constellation of different diseases with common themes. Precision imaging of such phenotypes requires flexible and tunable modalities capable of identifying phenotypic fingerprints by using a restricted number of parameters while ensuring sensitivity to dynamic biological regulation. Common phenotypes can be detected by in vivo imaging technologies, and effectively define the emerging standards for disease classification and patient stratification in radiology. However, for the imaging data to accurately represent a complex fingerprint, the individual imaging parameters need to be measured and analysed in relation to their wider spatial and molecular context. In this respect, targeted palettes of molecular imaging probes facilitate the detection of heterogeneity in oncogene-driven alterations and their response to treatment, and lead to the expansion of rational-design elements for the combination of imaging experiments. In this Review, we evaluate criteria for conducting multiplexed imaging, and discuss its opportunities for improving patient diagnosis and the monitoring of therapy.
Saleem A, Searle GE, Kenny LM, et al., 2017, Erratum to: Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer., EJNMMI Research, Vol: 7, Pages: 74-74, ISSN: 2191-219X
Theodorou I, Jawad Z, Jiang Q, et al., 2017, Gold Nanostar Substrates for Metal Enhanced Fluorescence through the First and Second Near-Infrared Windows, Chemistry of Materials, Vol: 29, Pages: 6916-6926, ISSN: 1520-5002
Gold nanostars (AuNSs) are receiving increasing attention for their potential applications in bionanotechnology because of their unique optical properties related to their complex branched morphology. Their sharp features allow strong localized surface plasmon resonances, tunable in the near-infrared (NIR) region, and large enhancements of local electromagnetic fields. Here, the application of AuNSs in metal-enhanced fluorescence (MEF) in the NIR and second NIR (NIR-II) biological windows is explored for the first time. NIR/NIR-II fluorophores are incorporated onto monolayers of AuNSs with tunable plasmonic responses. Over 320-fold fluorescence enhancement is achieved in the NIR, confirming that AuNS substrates are promising NIR-MEF platforms for the development of ultrasensitive biosensing applications. Using fluorescence lifetime measurements to semiquantitatively deconvolute the excitation enhancement from emission enhancement, as well as modeling to simulate the electric field enhancement, we show that a combination of enhanced excitation and an increased radiative decay rate, accompanied by an increase in the quantum yield, contribute to the observed large enhancement. AuNSs with different morphological features exhibit significantly different excitation enhancements, indicating the important role of the particle morphology on the magnitude of electromagnetic field enhancement and the resulting enhancement factor. Importantly, enhancement factors of up to 50-fold are also achieved in the NIR-II region, suggesting that this system holds promise for the future development of bright probes for NIR/NIR-II biosensing and bioimaging.
Lavdas I, Glocker B, Kamnitsas K, et al., 2017, Fully automatic, multi-organ segmentation in normal whole body magnetic resonance imaging (MRI), using classification forests (CFs), convolutional neural networks (CNNs) and a multi-atlas (MA) approach., Medical Physics, Vol: 44, Pages: 5210-5220, ISSN: 0094-2405
PURPOSE: As part of a programme to implement automatic lesion detection methods for whole body magnetic resonance imaging (MRI) in oncology, we have developed, evaluated and compared three algorithms for fully automatic, multi-organ segmentation in healthy volunteers. METHODS: The first algorithm is based on classification forests (CFs), the second is based on 3D convolutional neural networks (CNNs) and the third algorithm is based on a multi-atlas (MA) approach. We examined data from 51 healthy volunteers, scanned prospectively with a standardised, multi-parametric whole body MRI protocol at 1.5T. The study was approved by the local ethics committee and written consent was obtained from the participants. MRI data were used as input data to the algorithms, while training was based on manual annotation of the anatomies of interest by clinical MRI experts. Five-fold cross-validation experiments were run on 34 artefact-free subjects. We report three overlap and three surface distance metrics to evaluate the agreement between the automatic and manual segmentations, namely the Dice similarity coefficient (DSC), recall (RE), precision (PR), average surface distance (ASD), root mean square surface distance (RMSSD) and Hausdorff distance (HD). Analysis of variances was used to compare pooled label metrics between the three algorithms and the DSC on a 'per-organ' basis. A Mann-Whitney U test was used to compare the pooled metrics between CFs and CNNs and the DSC on a 'per-organ' basis, when using different imaging combinations as input for training. RESULTS: All three algorithms resulted in robust segmenters that were effectively trained using a relatively small number of data sets, an important consideration in the clinical setting. Mean overlap metrics for all the segmented structures were: CFs: DSC=0.70±0.18, RE=0.73±0.18, PR=0.71±0.14, CNNs: DSC=0.81±0.13, RE=0.83±0.14, PR=0.82±0.10, MA: DSC=0.71±0.22, RE=0.70±0.34
Calsolaro V, Femminella G, Fan Z, et al., 2017, Evaluation of caspase-3 activation in an Alzheimer’s disease population using [18F]ICMT-11 PET/CT, Alzheimer's and Dementia, Vol: 13, Pages: P1353-P1354, ISSN: 1552-5260
Aboagye EO, Kraeber-Bodéré F, 2017, Highlights lecture EANM 2016: "Embracing molecular imaging & multi-modal imaging: a smart move for nuclear medicine towards personalised medicine", European Journal of Nuclear Medicine and Molecular Imaging, Vol: 44, Pages: 1559-1574, ISSN: 1619-7089
The 2016 EANM Congress took place in Barcelona, Spain, from 15 to 19 October under the leadership of Prof. Wim Oyen, chair of the EANM Scientific Committee. With more than 6,000 participants, this congress was the most important European event in nuclear medicine, bringing together a multidisciplinary community involved in the different fields of nuclear medicine. There were over 600 oral and 1,200 poster or e-Poster presentations with an overwhelming focus on development and application of imaging for personalized care, which is timely for the community. Beyond FDG PET, major highlights included progress in the use of PSMA and SSTR receptor-targeted radiopharmaceuticals and associated theranostics in oncology. Innovations in radiopharmaceuticals for imaging pathologies of the brain and cardiovascular system, as well as infection and inflammation, were also highlighted. In the areas of physics and instrumentation, multimodality imaging and radiomics were highlighted as promising areas of research.
Sharma R, Wang WM, Evans J, et al., 2017, 68Ga-DOTATATE PET/CT to predict response to peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumours (NETs), ASCO, Publisher: American Society of Clinical Oncology, ISSN: 0732-183X
Challapalli A, Carroll L, Aboagye EO, 2017, Molecular mechanisms of hypoxia in cancer, Clinical and Translational Imaging, Vol: 5, Pages: 225-253, ISSN: 2281-5872
PurposeHypoxia is a condition of insufficient oxygen to support metabolism which occurs when the vascular supply is interrupted, or when a tumour outgrows its vascular supply. It is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. This review provides an overview of hypoxia imaging with Positron emission tomography (PET), with an emphasis on the biological relevance, mechanism of action, highlighting advantages, and limitations of the currently available hypoxia radiotracers.MethodsA comprehensive PubMed literature search was performed, identifying articles relating to biological significance and measurement of hypoxia, MRI methods, and PET imaging of hypoxia in preclinical and clinical settings, up to December 2016.ResultsA variety of approaches have been explored over the years for detecting and monitoring changes in tumour hypoxia, including regional measurements with oxygen electrodes placed under CT guidance, MRI methods that measure either oxygenation or lactate production consequent to hypoxia, different nuclear medicine approaches that utilise imaging agents the accumulation of which is inversely related to oxygen tension, and optical methods. The advantages and disadvantages of these approaches are reviewed, along with individual strategies for validating different imaging methods. PET is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels.ConclusionEven though hypoxia could have significant prognostic and predictive value in the clinic, the best method for hypoxia assessment has in our opinion not been realised.
Cysouw MCF, Kramer GM, Frings V, et al., 2017, Baseline and longitudinal variability of normal tissue uptake values of [F-18]-fluorothymidine-PET images, Nuclear Medicine and Biology, Vol: 51, Pages: 18-24, ISSN: 0969-8051
Purpose[18F]-fluorothymidine ([18F]-FLT) is a PET-tracer enabling in-vivo visualization and quantification of tumor cell proliferation. For qualitative and quantitative analysis, adequate knowledge of normal tissue uptake is indispensable. This study aimed to quantitatively investigate baseline tracer uptake of blood pool, lung, liver and bone marrow and their precision, and to assess the longitudinal effect of systemic treatment on biodistribution.Methods18F–FLT-PET(/CT) scans (dynamic or static) of 90 treatment-naïve oncological patients were retrospectively evaluated. Twenty-three patients received double baseline scans, and another 39 patients were also scanned early and late during systemic treatment with a tyrosine kinase inhibitor. Reproducible volume of interest were placed in blood pool, lung, liver, and bone marrow. For semi-quantitative analysis, SUVmean, SUVmax, and SUVpeak with several normalizations were derived.ResultsSUVs of basal lung, liver, and bone marrow were not significantly different between averaged dynamic and static images, in contrast with blood pool and apical lung. Highest repeatability was seen for liver and bone marrow, with repeatability coefficients of 18.6% and 20.4% when using SUVpeak. Systemic treatment with TKIs both increased and decreased normal tissue tracer uptake at early and late time points during treatment.ConclusionSimultaneous evaluation of liver and bone marrow uptake in longitudinal response studies may be used to assess image quality, where changes in uptake outside repeatability limits should trigger investigators to perform additional quality control on individual PET images.Advances in knowledgeFor [18F]-FLT PET images, liver and bone marrow have low intra-patient variability when quantified with SUVpeak, but may be affected by systemic treatment.Implications for patient careIn [18F]-FLT-PET response monitoring trials, liver and bone marrow uptake may be used for quality control of [18F]-FLT PET images
Valindria V, Lavdas I, Bai W, et al., 2017, Reverse classification accuracy: predicting segmentation performance in the absence of ground truth, IEEE Transactions on Medical Imaging, Vol: 36, Pages: 1597-1606, ISSN: 1558-254X
When integrating computational tools such as au-tomatic segmentation into clinical practice, it is of utmostimportance to be able to assess the level of accuracy on newdata, and in particular, to detect when an automatic methodfails. However, this is difficult to achieve due to absence of groundtruth. Segmentation accuracy on clinical data might be differentfrom what is found through cross-validation because validationdata is often used during incremental method development, whichcan lead to overfitting and unrealistic performance expectations.Before deployment, performance is quantified using differentmetrics, for which the predicted segmentation is compared toa reference segmentation, often obtained manually by an expert.But little is known about the real performance after deploymentwhen a reference is unavailable. In this paper, we introduce theconcept ofreverse classification accuracy(RCA) as a frameworkfor predicting the performance of a segmentation method onnew data. In RCA we take the predicted segmentation froma new image to train a reverse classifier which is evaluatedon a set of reference images with available ground truth. Thehypothesis is that if the predicted segmentation is of good quality,then the reverse classifier will perform well on at least some ofthe reference images. We validate our approach on multi-organsegmentation with different classifiers and segmentation methods.Our results indicate that it is indeed possible to predict the qualityof individual segmentations, in the absence of ground truth. Thus,RCA is ideal for integration into automatic processing pipelines inclinical routine and as part of large-scale image analysis studies.
Schelhaas S, Heinzmann K, Bollineni V, et al., 2017, Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review, Theranostics, Vol: 7, Pages: 40-50, ISSN: 1838-7640
The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies.
Sharma R, Mapelli P, Hanna GB, et al., 2016, Evaluation of F-18-fluorothymidine positron emission tomography ([F-18] FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer, EJNMMI Research, Vol: 6, ISSN: 2191-219X
Background3’-Deoxy-3’-[18F]fluorothymidine ([18F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [18F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy.Dynamic [18F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy. Changes in tumour [18F]FLT-PET/CT variables were determined. Response was determined on contrast-enhanced CT after three cycles of therapy using RECIST 1.1.ResultsTen patients were included. Following application of the KSF, visual distinction of all oesophageal and/or gastric tumours was observed in [18F]FLT-PET images. Among the nine patients available for response evaluation (RECIST 1.1), three patients had responded (partial response) and six patients were non-responders (stable disease). There was a significant association between Ki-67 and all baseline [18F]FLT-PET parameters. Area under the curve (AUC) from 0 to 1 min was associated with treatment response.ConclusionsThe results of this study indicate that application of the KSF allowed accurate visualisation of both primary and metastatic lesions following imaging with the proliferation marker, [18F]FLT-PET/CT. However, [18F]FLT-PET uptake parameters did not correlate with response. Instead, we observe significant changes in tracer delivery following chemotherapy suggesting that further [18F]FLT-PET/CT studies in this tumour type should be undertaken with caution.
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