Lin M.-Y.,Peter MacCallum Cancer Center |
Wu M.,Peter MacCallum Cancer Center |
Brennan S.,Peter MacCallum Cancer Center |
Campeau M.-P.,Peter MacCallum Cancer Center |
And 5 more authors.
Journal of Thoracic Oncology | Year: 2014
INTRODUCTION: A recent meta-analysis suggested that patients with non-small-cell lung cancer (NSCLC) whose primary tumors have a higher standardized uptake value (SUV) derived from F-fluorodeoxyglucose positron emission tomography (PET) have a worse prognosis in comparison with those with tumors with lower values. However, previous analyses have had methodological weaknesses. Furthermore, the prognostic significance over the full range of SUV values in patients treated nonsurgically remains unclear. The aim of this retrospective study was to investigate the relationship between survival and maximum SUV (SUVmax) analyzed as a continuous variable, in patients with NSCLC, staged using PET/computed tomography (CT) and treated with radiotherapy with or without chemotherapy. METHODS: Eligible patients had a histological diagnosis of NSCLC, were treated with radical radiotherapy with or without chemotherapy as their primary treatment, and had pretreatment PET/CT scans. SUVmax, defined as the maximum pixel SUV value retrieved from the primary tumor, was analyzed primarily as a continuous variable for overall survival. RESULTS: Eighty-eight patients met eligibility criteria: stage I, 19; stage II, 10; and stage III, 59. Median SUVmax was 15.0 (range, 2.5-56). Higher stage was associated with higher SUVmax values (p = 0.048). In univariate analysis, there was no evidence of a prognostic effect of SUVmax (hazard ratio per doubling = 0.83; 95% confidence interval, 0.62-1.11; p = 0.22). Analyzing SUVmax as a dichotomous variable (median cut point = 15.0), the hazard ratio (high: low) for risk of death was 0.71, with p = 0.18 (95% confidence interval, 0.44-1.15). CONCLUSIONS: In this cohort of patients, increasing SUVmax derived from F-fluorodeoxyglucose-PET/CT was associated with increasing tumor, node, metastasis (TNM) stage. We found no evidence of an association of increasing SUVmax with a shorter survival. Previous reports of an association between prognosis and SUVmax may partly be the result of methodological differences between this study and previous reports and an association between stage and SUVmax. Copyright © 2014 by the International Association for the Study of Lung Cancer.
Aide N.,Francois Baclesse Cancer Center |
Aide N.,University of Caen Lower Normandy |
Visser E.P.,Radboud University Nijmegen |
Lheureux S.,University of Caen Lower Normandy |
And 4 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2012
Over the last decade, small-animal PET imaging has become a vital platform technology in cancer research. With the development of molecularly targeted therapies and drug combinations requiring evaluation of different schedules, the number of animals to be imaged within a PET experiment has increased. This paper describes experimental design requirements to reach statistical significance, based on the expected change in tracer uptake in treated animals as compared to the control group, the number of groups that will be imaged, and the expected intra-animal variability for a given tracer. We also review how high-throughput studies can be performed in dedicated small-animal PET, high-resolution clinical PET systems and planar positron imaging systems by imaging more than one animal simultaneously. Customized beds designed to image more than one animal in large-bore small-animal PET scanners are described. Physics issues related to the presence of several rodents within the field of view (i.e. deterioration of spatial resolution and sensitivity as the radial and the axial offsets increase, respectively, as well as a larger effect of attenuation and the number of scatter events), which can be assessed by using the NEMA NU 4 image quality phantom, are detailed. © 2012 The Author(s).
The world renowned Memorial Sloan Kettering Cancer Center in New York City uses a Renishaw inVia confocal Raman microscope, in the Kircher Laboratory, to support the development of nanomolecular probes
News Article | March 4, 2016
Home > Press > The world-renowned Memorial Sloan Kettering Cancer Center in New York City uses a Renishaw inVia confocal Raman microscope, in the Kircher Laboratory, to support the development of nanomolecular probes Abstract: The Kircher laboratory at Memorial Sloan Kettering is developing novel nanoprobes for molecular imaging, image-guided therapy and theranostics. Its ultimate goal is to develop a universal technology that allows precise determination of the actual spread of a tumour in vivo. Currently surgeons cannot see the microscopic extent of the tumour during a procedure, which is essential information for tumor removal and avoiding excess tissue excision. Physician-scientist Dr. Moritz Kircher is working on a new generation of nanometer-sized imaging beacons. These allow detection, during surgeries and minimally invasive procedures, of the macroscopic extent of the primary tumour, its true microscopic spread, as well information on satellite micrometastases. These nanobeacons can be located using surface enhanced resonance Raman scattering (SERRS), which can be combined with other whole-body imaging methods, such as magnetic resonance imaging (MRI) or positron emission tomography (PET). SERRS is a highly sensitive technique utilising a resonance Raman effect, combined with a surface enhancement obtained from nanoparticles to give dramatic enhancements to the normally weak Raman signal. The advantages of the SERRS method is also utilised by Renishaw Diagnostics in their recently launched CE certified RenDX Fungiplex assay IVD device. Dr. Kircher is a member of the Department of Radiology, the Center for Molecular Imaging and Nanotechnology and the Brain Tumor Center. He chose the Renishaw inVia confocal Raman microscope for the Kircher Laboratory, following his positive experience of using the instrumentand the successful research he obtainedduring his post-doctoral studies at Stanford University, in the group of Professor Sam Gambhir. He has gone on to publish several high profile papers using inVia's results.1 Dr. Kircher said, Our aims are to visualise any cancer type with the ultrasensitive Raman nanostar particles my group has developed. This includes providing high precision intraoperative guidance to surgeons, so that they can, with confidence, visualise and excise all cancer cells completely and without having to sacrifice too much normal tissue around the tumour. In addition, our SERRS nanoparticles are not only universal with regards to tumour type, they also allow us to detect microscopic tumour extensions from the main tumour into the periphery, microscopic loco regional metastases and even premalignant lesions. Most recently, the group has published an overview paper in the Journal of Nuclear Medicine2 which cites SERRS as a new modality for cancer imaging. The authors concluded that the increased accuracy in visualising the full extent of tumour spread provided by the SERRS signal could increase the precision with which cancers can be resected or destroyed, be it via open surgery or minimally invasive techniques used by interventional radiologists. With the application of SERRS in diagnostics and cancer detection the future for the application of Raman spectroscopy in this field looks very promising. For further details about Renishaw's inVia confocal Raman microscope, visitwww.renishaw.com/invia. References 1 Surface-enhanced resonance Raman scattering nanostars for high-precision cancer imaging, Harmsen et al, Science Translational Medicine 21 Jan 2015: Vol. 7, Issue 271, pp. 271ra7, DOI: 10.1126/scitranslmed.3010633 2 Surface-Enhanced Raman Spectroscopy: A New Modality for Cancer Imaging, Andreou, Kishore & Kircher, J Nucl Med 2015; 56:15, DOI: 10.2967/jnumed.115.158196 Acknowledgement Professor S Maruyama and Dr S Chiashi would like to acknowledge the co-operation of the Laser Alliance at Institute of Engineering Innovation, School of Engineering, University of Tokyo. About Renishaw Renishaw is one of the world's leading engineering and scientific technology companies, with expertise in precision measurement and healthcare. The company supplies products and services used in applications as diverse as jet engine and wind turbine manufacture, through to dentistry and brain surgery. It is also a world leader in the field of additive manufacturing (also referred to as 3D printing), where it is the only UK business that designs and makes industrial machines which print parts from metal powder. The Renishaw Group currently has more than 70 offices in 33 countries, with around 4,000 employees, of which 2,700 people are employed within the UK. The majority of the company's R&D and manufacturing is carried out in the UK and for the year ended June 2015 Renishaw achieved sales of £494.7 million of which 95% was due to exports. The company's largest markets are the USA, China, Germany and Japan. The Company's success has been recognised with numerous international awards, including eighteen Queen's Awards recognising achievements in technology, export and innovation. Renishaw received a Queen's Award for Enterprise 2014, in the Innovations category, for the continuous development of the inVia confocal Raman microscope. 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Callahan J.,Center for Molecular Imaging |
Binns D.,Center for Molecular Imaging |
Dunn L.,RMIT University |
Kron T.,Peter MacCallum Cancer Center
Australasian Physical and Engineering Sciences in Medicine | Year: 2011
To assess the effect of lesion motion and respiration rate on Standardised Uptake Value (SUV) and the ability of 4D PET to restore any loss in SUV and distortion of lesion volume on two PET/CT systems. A Perspex phantom with four cylindrical reservoirs filled with 18F-FDG was used in this study. The cylinders measured 5, 10, 15, and 20 mm in diameter. A GE Discovery STE8 (GE Medical Systems Milwaukee, WI) and a Siemens Biograph 64/40 (Siemens Medical Solutions, Erlangen, Germany) scanner was used to acquire a stationary un-gated PET scan of the phantom. Multiple 10 min list mode 4D PET scans were acquired using the Varian RPM on the GE camera and the Anzai Gating system on the Siemens camera. The phantom was scanned at five different respiratory rates and motion amplitudes in a sinusoidal fashion, 15 RPM/1 cm, 15 RPM/2 cm, 15 RPM/4 cm, 30 RPM/2 cm and 7.5 RPM/2 cm (RPM-respirations per minute). Each scan was reconstructed into ten bins and as an un-gated static image. The SUVmax, SUVmean and volume were measured for all four reservoirs using Siemens TrueD analysis software. With increasing lesion movement the SUVmax and SUVmean decreased and the volume increased with the SUVmax in the smallest lesion underestimated by up to a factor of four. The SUVmax, SUVmean and volume were mostly recovered using 4D imaging regardless of amount of lesion displacement. The larger lesions showed better count recovery and volume correction than the smaller lesions. The respiratory rate had no effect of SUV or volume. Un-gated imaging of moving lesions decreases apparent SUV in small lesions significantly and overestimates volumes. 4D PET scanning recovers most of the apparent loss in SUV and distortion of volumes. © 2011 Australasian College of Physical Scientists and Engineers in Medicine.
Ma M.T.,University of Melbourne |
Neels O.C.,Center for Molecular Imaging |
Denoyer D.,Center for Molecular Imaging |
Roselt P.,Center for Molecular Imaging |
And 5 more authors.
Bioconjugate Chemistry | Year: 2011
Tumor-targeting peptides radiolabeled with positron-emitting 68Ga are promising candidates as new noninvasive diagnostic agents for positron emission tomography (PET). The targeting peptides are tethered to a chelator that forms a stable coordination complex with Ga 3+ that is inert to dissociation of Ga 3+in vivo. Metal complexes of macrobicyclic hexaamine "sarcophagine" (sar = 3,6,10,13,16,19- hexaazabicyclo[6.6.6]icosane) ligands exhibit remarkable stability as a result of the encapsulating nature of the cage amine ligand. A Ga 3+ sarcophagine complex, [Ga-(1-NH 3-8-NH 2-sar)] 4+, has been characterized using X-ray crystallography, demonstrating that Ga 3+ is coordinated to six nitrogen atoms in a distorted octahedral complex. A bifunctional derivative of (NH 2) 2sar, possessing two aliphatic linkers with carboxylic acid functional groups has been attached to two cyclic-RGD peptides that target the ? v? 3 integrin receptor that is overexpressed in some types of tumor tissue. This dimeric species can be radiolabeled with 68Ga 3+ in >98% radiochemical yield and 68Ga 3+ does not dissociate from the ligand in the presence of transferrin, an endogenous protein with high affinity for Ga 3+. Biodistribution and micro-PET imaging studies in tumor-bearing mice indicate that the tracer accumulates specifically in tumors with high integrin expression. The high tumor uptake is coupled with low nonspecific uptake and clearance predominantly through the kidneys resulting in high-quality PET images in animal models. © 2011 American Chemical Society.
Fathinul F.,University Putra Malaysia |
Nordin A.J.,University Putra Malaysia |
Lau W.F.E.,University of Melbourne |
Lau W.F.E.,Center for Molecular Imaging
Cell Biochemistry and Biophysics | Year: 2013
Molecular imaging employing 18[F]FDG-PET/CT enables in-vivo visualization, characterisation and measurement of biological process in tumour at the molecular and cellular level. In oncology, this approach can be directly applied as translational biomarkers of disease progression. In this article, the improved roles of FDG as an in-vivo glycolytic marker which reflect biological changes across in-vitro cellular environment are discussed. New understanding in how altered metabolism via glycolytic downstream drivers of malignant transformation as reviewed below offers unique promise as to monitor tumour aggressiveness and hence optimize the therapeutic management. © 2012 Springer Science+Business Media, LLC.
Hubble D.,Center for Molecular Imaging |
Kong G.,Center for Molecular Imaging |
Michael M.,Center for Molecular Imaging |
Johnson V.,Center for Molecular Imaging |
And 2 more authors.
European Journal of Nuclear Medicine and Molecular Imaging | Year: 2010
Purpose The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity 111In-pentetreotide can be safely treated with 177Lu- octreotate and whether addition of radiosensitising chemotherapy increases the toxicity of this agent. Methods Records of 27 patients (aged 17-75) who received 69 (median 3 per patient) 177Lu-octreotate administrations, including 29 in conjunction with radiosensitising infusional 5-fluorouracil (5-FU) (n=27), or capecitabine (n=2), between October 2005 and July 2007 subsequent to 1-8 prior cycles of 111In-pentetreotide therapy were analysed. Toxicity was assessed during and at 8-12 weeks post-treatment, with further long-term assessments including survival status reviewed till death or study close-out date of 1 November 2009. Results Reduction in blood counts was most marked following the first dose of 177Lu-octreotate but at early follow-up the only major haematological toxicity was a single case of grade 4 lymphopaenia. Both the presence of bone metastases and the administration of chemotherapy tended to result in greater reduction in blood counts, but these differences did not reach statistical significance. On long-term follow-up, 16 patients (59%) are alive with median overall survival of 36 months (32-44 months from first 177Lu-octreotate therapy). None of the recorded deaths was directly related to treatment toxicity. One patient had late grade 4 anaemia and thrombocytopaenia secondary to bone marrow failure from progressive infiltration by tumour. No other significant long-term haematological toxicities were recorded and no leukaemia was observed. No renal toxicity was observed on serial serum creatinine or radionuclide glomerular filtration rate (GFR) determination on initial or long-term follow-up. Conclusion 177Lu- octreotate is a safe and well-tolerated therapy for patients who have previously been treated with 111In-pentetreotide and can be safely combined with radio-sensitising chemotherapy. However, caution is recommended in patients with bone metastases. Significant late toxicities including bone marrow or renal failure, or leukaemia directly related to radionuclide therapy, did not occur in our series. © Springer-Verlag 2010.
Feyen O.,TAVARLIN AG |
Coy J.F.,TAVARLIN AG |
Prasad V.,Center for Molecular Imaging |
Prasad V.,Charite University Hospital |
And 3 more authors.
Future Oncology | Year: 2012
Aim: To determine whether the TKTL1 protein epitope detection in monocytes (EDIM) test allows detection of upregulated glucose metabolism in malignancies. Materials & methods: The EDIM-TKTL1 blood test was conducted in 240 patients with 17 different confirmed or suspected malignancies. Test scores were compared with 18F-fluoro-2-deoxy-D-glucose (FDG)-PET/computed tomography (CT) results. Results: EDIM-TKTL1 score and FDG-PET results showed a concordance of 90% with a sensitivity of 94% and specificity of 81%. Including CT data, all values were enhanced. A subgroup analysis of non-small-cell lung cancer patients showed a significant correlation between the EDIM-TKTL1 score and the primary tumor size determined by FDG-PET/CT. Conclusion: EDIM-TKTL1 blood test revealed good concordance with FDG-PET/CT results in patients with malignancies demonstrating its efficacy to detect upregulation of glucose metabolism in primary tumors or metastases. © 2012 Oliver Feyen.
Luker K.E.,Center for Molecular Imaging |
Steele J.M.,Center for Molecular Imaging |
Mihalko L.A.,Center for Molecular Imaging |
Ray P.,Center for Molecular Imaging |
And 2 more authors.
Oncogene | Year: 2010
CXCR7 is a receptor for chemokines including CXCL12 (stromal-derived factor-1), a molecule that promotes tumor growth and metastasis in breast cancer and other malignancies. Building on the recent observation that CXCR7 sequesters CXCL12, we investigated mechanisms for CXCR7-dependent uptake of chemokines. Breast cancer cells expressing CXCR7 accumulated chemokines CXCL12 and CXC11 present at concentrations 1 ng/ml, unlike cells expressing CXCR4. CXCR7-dependent accumulation of chemokines was reduced by inhibitors of clathrin-mediated endocytosis. After CXCR7-mediated internalization, CXCL12 trafficked to lysosomes and was degraded, although levels of CXCR7 remained stable. CXCR7 reduced CXCL12 in the extracellular space, limiting the amounts of chemokine available to acutely stimulate signaling through CXCR4. CXCR7 constitutively internalized and recycled to the cell membrane even in the absence of ligand, and addition of chemokines did not significantly enhance receptor internalization. Chemokines at concentrations less than the Kd values for ligand-receptor binding did not alter levels of CXCR7 at the cell surface. Higher concentrations of chemokine ligands reduced the total cell surface expression of CXCR7 without affecting receptor internalization, indicating that receptor recycling was inhibited. CXCR7-dependent uptake of chemokines and receptor trafficking were regulated by Β-arrestin 2. These studies establish mechanisms through which CXCR7 regulates the availability of chemokine ligands in the extracellular space. © 2010 Macmillan Publishers Limited All rights reserved.
Hofman M.S.,Center for Molecular Imaging |
Hofman M.S.,University of Melbourne |
Hicks R.J.,Center for Molecular Imaging |
Hicks R.J.,University of Melbourne
Seminars in Nuclear Medicine | Year: 2016
Nuclear medicine renal imaging provides important functional data to assist in the diagnosis and management of patients with a variety of renal disorders. Physiologically stable metal chelates like ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine penta-acetate (DTPA) are excreted by glomerular filtration and have been radiolabelled with a variety of isotopes for imaging glomerular filtration and quantitative assessment of glomerular filtration rate. Gallium-68 (68Ga) EDTA PET usage predates Technetium-99m (99mTc) renal imaging, but virtually disappeared with the widespread adoption of gamma camera technology that was not optimal for imaging positron decay. There is now a reemergence of interest in 68Ga owing to the greater availability of PET technology and use of 68Ga to label other radiotracers. 68Ga EDTA can be used a substitute for 99mTc DTPA for wide variety of clinical indications. A key advantage of PET for renal imaging over conventional scintigraphy is 3-dimensional dynamic imaging, which is particularly helpful in patients with complex anatomy in whom planar imaging may be nondiagnostic or difficult to interpret owing to overlying structures containing radioactive urine that cannot be differentiated. Other advantages include accurate and absolute (rather than relative) camera-based quantification, superior spatial and temporal resolution and integrated multislice CT providing anatomical correlation. Furthermore, the 68Ga generator enables on-demand production at low cost, with no additional patient radiation exposure compared with conventional scintigraphy. Over the past decade, we have employed 68Ga EDTA PET/CT primarily to answer difficult clinical questions in patients in whom other modalities have failed, particularly when it was envisaged that dynamic 3D imaging would be of assistance. We have also used it as a substitute for 99mTc DTPA if unavailable owing to supply issues, and have additionally examined the role of 68Ga EDTA PET/CT for measuring glomerular filtration rate and split renal function. © 2016 Elsevier Inc.