Publications
98 results found
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
Kramer GM, Liu Y, de langen AJ, et al., 2016, Repeatability of Quantitative <SUP>18</SUP>F-FLT Uptake Measurements in Solid Tumors: A multi-centre Meta-Analysis, Annual Congress of the European-Association-of-Nuclear-Medicine, Publisher: SPRINGER, Pages: S357-S358, ISSN: 1619-7070
Palmieri C, Szydlo R, Miller M, et al., 2016, The effects of the first in class steroid sulfatase inhibitor Irosustat on FLT uptake and Ki67 in estrogen receptor positive early breast cancer: Results of the perioperative IPET study., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
Kenny L, 2016, The Use of Novel PET Tracers to Image Breast Cancer Biologic Processes Such as Proliferation, DNA Damage and Repair, and Angiogenesis, JOURNAL OF NUCLEAR MEDICINE, Vol: 57, Pages: 89S-95S, ISSN: 0161-5505
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- Citations: 20
Harada N, Varghese V, Xie L, et al., 2015, Targeting lactate metabolism as a novel therapeutic target in platinum-resistant triple negative breast cancer (TNBC), 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
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- Citations: 1
Merchant S, Aboagye EO, Lim A, et al., 2015, Evaluation of apoptosis in breast cancer using the novel PET probe [<SUP>18</SUP>F]ICMT-11 in patients treated with neoadjuvant FEC chemotherapy: Initial assessment of optimum imaging time and relation to caspase-3 immunostaining, 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
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- Citations: 1
Saleem A, Searle GE, Kenny LM, et al., 2015, Lapatinib access into normal brain and brain metastases in patients with Her-2 overexpressing breast cancer, EJNMMI Research, Vol: 5, ISSN: 2191-219X
BackgroundBrain metastases are common in human epidermal growth factor receptor (Her)-2-positive breast cancer. Drug access to brain metastases and normal brain is key to management of cranial disease. In this study, positron emission tomography (PET) scanning after administration of radiolabelled lapatinib was used to obtain direct evidence of cranial drug access.MethodsPatients with Her-2+ metastatic breast cancer either with at least one 1-cm diameter brain metastasis or without brain metastases underwent dynamic carbon-11 radiolabelled lapatinib ([11C]lapatinib)-PET. Less than 20 μg of [11C]lapatinib was administered before and after 8 days of oral lapatinib (1,500 mg once daily). Radial arterial blood sampling was performed throughout the 90-min scan. The contribution of blood volume activity to the tissue signal was excluded to calculate lapatinib uptake in normal brain and metastases. Partitioning of radioactivity between plasma and tissue (V T) was calculated and the tissue concentration of lapatinib derived. Plasma lapatinib levels were measured and adverse events noted.ResultsSix patients (three with brain metastases) were recruited. About 80% plasma radioactivity corresponded to intact [11C]lapatinib after 60 min. PET signal in the brain corresponded to circulating radioactivity levels, with no [11C]lapatinib uptake observed in normal brain tissue. In contrast, radioactivity uptake in cranial metastases was significantly higher (p = 0.002) than that could be accounted by circulating radioactivity levels, consistent with [11C]lapatinib uptake in brain metastases. There was no difference in lapatinib uptake between the baseline and day 8 scans, suggesting no effect of increased drug access by inhibition of the drug efflux proteins by therapeutic doses of lapatinib.ConclusionsIncreased lapatinib uptake was observed in brain metastases but not in normal brain.
Hoyng LL, Frings V, Hoekstra OS, et al., 2015, Metabolically active tumour volume segmentation from dynamic [<SUP>18</SUP>F] FLT PET studies in non-small cell lung cancer, EJNMMI RESEARCH, Vol: 5, ISSN: 2191-219X
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- Citations: 2
Femminella GD, Kenny LM, Sinha A, et al., 2015, Carcinoid-associated Encephalopathy, JOURNAL OF CLINICAL GASTROENTEROLOGY, Vol: 49, Pages: 353-354, ISSN: 0192-0790
Varghese V, Magnani L, Harada N, et al., 2015, Inhibition of FOXM1 by thiostrepton increases sensitivity to 5-fluorouracil (5-FU) by downregulating thymidylate synthase (TS) in colorectal cancer, AACR Precision Medicine Conference on Drug Sensitivity and Resistance - Improving Cancer Therapy, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 1078-0432
Blighe K, Kenny L, Patel N, et al., 2014, Whole Genome Sequence Analysis Suggests Intratumoral Heterogeneity in Dissemination of Breast Cancer to Lymph Nodes, PLOS One, Vol: 9, ISSN: 1932-6203
Background: Intratumoral heterogeneity may help drive resistance to targetedtherapies in cancer. In breast cancer, the presence of nodal metastases is a keyindicator of poorer overall survival. The aim of this study was to identify somaticgenetic alterations in early dissemination of breast cancer by whole genome nextgeneration sequencing (NGS) of a primary breast tumor, a matched locally-involvedaxillary lymph node and healthy normal DNA from blood.Methods: Whole genome NGS was performed on 12 mg (range 11.1–13.3 mg) ofDNA isolated from fresh-frozen primary breast tumor, axillary lymph node andperipheral blood following the DNA nanoball sequencing protocol. Single nucleotidevariants, insertions, deletions, and substitutions were identified through abioinformatic pipeline and compared to CIN25, a key set of genes associated withtumor metastasis.Results: Whole genome sequencing revealed overlapping variants between thetumor and node, but also variants that were unique to each. Novel mutations uniqueto the node included those found in two CIN25 targets, TGIF2 and CCNB2, whichare related to transcription cyclin activity and chromosomal stability, respectively,and a unique frameshift in PDS5B, which is required for accurate sister chromatidsegregation during cell division. We also identified dominant clonal variants thatprogressed from tumor to node, including SNVs in TP53 and ARAP3, whichmediates rearrangements to the cytoskeleton and cell shape, and an insertion in TOP2A, the expression of which is significantly associated with tumor proliferationand can segregate breast cancers by outcome.Conclusion: This case study provides preliminary evidence that primary tumor andearly nodal metastasis have largely overlapping somatic genetic alterations. Therewere very few mutations unique to the involved node. However, significantconclusions regarding early dissemination needs analysis of a larger number ofpatient samples.
Kenny LM, Aboagye EO, 2014, Clinical Translation of Molecular Imaging Agents Used in PET Studies of Cancer, EMERGING APPLICATIONS OF MOLECULAR IMAGING TO ONCOLOGY, Vol: 124, Pages: 329-374, ISSN: 0065-230X
Varghese V, Magnani L, Harada N, et al., 2014, Forkhead box transciption factor M1 (FOXM1) plays a critical role in colorectal cancer resistance by regulating thymidylate synthase (TS), 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR), Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Kenny LM, Tomasi G, Turkheimer F, et al., 2014, Preliminary clinical assessment of the relationship between tumor alphavbeta3 integrin and perfusion in patients studied with [<SUP>18</SUP>F]fluciclatide kinetics and [<SUP>15</SUP>O]H<sub>2</sub>O PET, EJNMMI RESEARCH, Vol: 4, ISSN: 2191-219X
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- Citations: 2
Tharayil IA, Harada N, Patel N, et al., 2013, Measurement of tumour lesion glycolysis by FDG-PET in triple negative breast cancer, CANCER RESEARCH, Vol: 73, ISSN: 0008-5472
Harada N, Varghese V, Tharayil IA, et al., 2013, Metformin has an additive effect to cisplatin in triple negative breast cancer cells with high lactate dehydrogenase B (LDHB) expression, CANCER RESEARCH, Vol: 73, ISSN: 0008-5472
Kenny LM, 2013, 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib, trastuzumab, and their combination in HER2-positive breast cancer: results from Neo-ALTTO., J Nucl Med, Vol: 54, Pages: 1855-1856
Challapalli A, Kenny LM, Hallett WA, et al., 2013, <SUP>18</SUP>F-ICMT-11, a Caspase-3-Specific PET Tracer for Apoptosis: Biodistribution and Radiation Dosimetry, JOURNAL OF NUCLEAR MEDICINE, Vol: 54, Pages: 1551-1556, ISSN: 0161-5505
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- Citations: 75
Saleem A, Searle G, Kenny LM, et al., 2013, Brain and tumor penetration of carbon-11-labeled lapatinib ([<SUP>11</SUP>C]Lap) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC), 49th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
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- Citations: 2
Willaime JMY, Turkheimer FE, Kenny LM, et al., 2013, Quantification of intra-tumour cell proliferation heterogeneity using imaging descriptors of 18F fluorothymidine-positron emission tomography, Physics in medicine and biology, Vol: 58, Pages: 187-203
Intra-tumour heterogeneity is a characteristic shared by all cancers. We explored the use of texture variables derived from images of [(18)F]fluorothymidine-positron emission tomography (FLT-PET), thus notionally assessing the heterogeneity of proliferation in individual tumours. Our aims were to study the range of textural feature values across tissue types, verify the repeatability of these image descriptors and further, to explore associations with clinical response to chemotherapy in breast cancer patients. The repeatability of 28 textural descriptors was assessed in patients who had two FLT-PET scans prior to therapy using relative differences and the intra-class correlation coefficient (ICC). We tested associations between features at baseline and clinical response measured in 11 patients after three cycles of chemotherapy, and explored changes in FLT-PET at one week after the start of therapy. A subset of eight features was characterized by low variations at baseline (<30%) and high repeatability (0.7 ≤ ICC ≤ 1). The intensity distribution profile suggested fewer highly proliferating cells in lesions of non-responders compared to responders at baseline. A true increase in CV and homogeneity was measured in four out of six responders one week after the start of therapy. A number of textural features derived from FLT-PET are altered following chemotherapy in breast cancer, and should be evaluated in larger clinical trials for clinical relevance.
Cseh Z, Kenny L, Swingland J, et al., 2013, Neural Networks Combined with Region Growing Techniques for Tumor Detection in [<SUP>18</SUP>F]-Fluorothymidine Dynamic Positron Emission Tomography Breast Cancer Studies, Conference on Medical Imaging - Computer-Aided Diagnosis, Publisher: SPIE-INT SOC OPTICAL ENGINEERING, ISSN: 0277-786X
Monteiro LJ, Khongkow P, Kongsema M, et al., 2012, The Forkhead Box M1 protein regulates BRIP1 expression and DNA damage repair in epirubicin treatment, Oncogene, Vol: 32, Pages: 4634-4645, ISSN: 1476-5594
FOXM1 is implicated in genotoxic drug resistance but its role and mechanism of action remain unclear. Here, we establish that γH2AX foci, indicative of DNA double-strand breaks (DSBs), accumulate in a time-dependent manner in the drug-sensitive MCF-7 cells but not in the resistant counterparts in response to epirubicin. We find that FOXM1 expression is associated with epirubicin sensitivity and DSB repair. Ectopic expression of FOXM1 can increase cell viability and abrogate DSBs sustained by MCF-7 cells following epirubicin, owing to an enhancement in repair efficiency. Conversely, alkaline comet and γH2AX foci formation assays show that Foxm1-null cells are hypersensitive to DNA damage, epirubicin and γ-irradiation. Furthermore, we find that FOXM1 is required for DNA repair by homologous recombination (HR) but not non-homologous end joining (NHEJ), using HeLa cell lines harbouring an integrated direct repeat green fluorescent protein reporter for DSB repair. We also identify BRIP1 as a direct transcription target of FOXM1 by promoter analysis and chromatin-immunoprecipitation assay. In agreement, depletion of FOXM1 expression by small interfering RNA downregulates BRIP1 expression at the protein and mRNA levels in MCF-7 and the epirubicin-resistant MCF-7 EpiR cells. Remarkably, the requirement for FOXM1 for DSB repair can be circumvented by reintroduction of BRIP1, suggesting that BRIP1 is an important target of FOXM1 in DSB repair. Indeed, like FOXM1, BRIP1 is needed for HR. These data suggest that FOXM1 regulates BRIP1 expression to modulate epirubicin-induced DNA damage repair and drug resistance.
Hoyng LL, Tomasi G, Hoekstra OS, et al., 2012, Tumour volume segmentation from dynamic [<SUP>18</SUP>F]FLT data, 25th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), Publisher: SPRINGER, Pages: S369-S369, ISSN: 1619-7070
Aboagye EO, Gilbert FJ, Fleming IN, et al., 2012, Recommendations for measurement of tumour vascularity with positron emission tomography in early phase clinical trials, EUROPEAN RADIOLOGY, Vol: 22, Pages: 1465-1478, ISSN: 0938-7994
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- Citations: 12
Contractor K, Challapalli A, Tomasi G, et al., 2012, Imaging of cellular proliferation in liver metastasis by [<SUP>18</SUP>F]fluorothymidine positron emission tomography: effect of therapy, PHYSICS IN MEDICINE AND BIOLOGY, Vol: 57, Pages: 3419-3433, ISSN: 0031-9155
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- Citations: 16
Contractor KB, Kenny LM, Coombes CR, et al., 2012, Evaluation of limited blood sampling population input approaches for kinetic quantification of [<SUP>18</SUP>F]fluorothymidine PET data, EJNMMI RESEARCH, Vol: 2, ISSN: 2191-219X
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- Citations: 12
Willaime JMY, Turkheimer FE, Kenny LM, et al., 2012, Image descriptors of intra-tumor proliferative heterogeneity predict chemotherapy response in breast tumors, http://jnumedmtg.snmjournals.org/cgi/content/meeting_abstract/53/1_MeetingAbstracts/387, SNM Annual Meeting, Publisher: J Nucl Med
Tomasi G, Kenny L, Mauri F, et al., 2011, Quantification of receptor-ligand binding with [<SUP>18</SUP>F]fluciclatide in metastatic breast cancer patients, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 38, Pages: 2186-2197, ISSN: 1619-7070
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- Citations: 39
Mapelli P, Aboagye E, Al-Nahhas A, et al., 2011, Effect of Fluorouracil-Epirubicin-Cyclophosphamide (FEC) chemotherapy on physiological bone marrow proliferation in breast cancer patients measured by <SUP>18</SUP>F-FLT PET, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 38, Pages: S231-S231, ISSN: 1619-7070
Kenny LM, Lam EWF, 2011, Lapatinib in metastatic colorectal cancer-another strategy for disease control?, Clinical Advances in Hematology and Oncology, Vol: 9, Pages: 500-501, ISSN: 1543-0790
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- Citations: 2
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