The potential of optical proteomic technologies to individualize prognosis and guide rational tre... more The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients
Background Systemic cancer spread is preceded by the establishment of a permissive microenvironme... more Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming. Methods A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy. Results S100A8/A9 imaging reflected MDSC abunda...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, May 3, 2015
Loco-regional recurrence of breast cancer poses significant clinical problems due to frequent ino... more Loco-regional recurrence of breast cancer poses significant clinical problems due to frequent inoperability once the chest wall is involved. Early detection of recurrence by molecular imaging agents against therapeutically targetable receptors, such as c-Met, would be of potential benefit. The aim of this study was to assess [(18)F]AH113804,a peptide-based molecular imaging agent with high affinity for human c-Met, for the detection of early stage loco-regional recurrence in a human basal-like breast cancer model, HCC1954. HCC1954 tumor-bearing xenograft models were established, and [(18)F]AH113804 was administered. Distribution of radioactivity was determined via positron emission tomography (PET) at 60 min post radiotracer injection. PET and CT (computerized tomography) images were acquired 10 days after tumor inoculation, to establish baseline distribution and uptake, and then on selected days after surgical tumor resection. CT images and caliper were used to determine the tumor ...
Confocal, Multiphoton, and Nonlinear Microscopic Imaging, 2003
We demonstrate the applicability of time-correlated single photon counting multiphoton microscopy... more We demonstrate the applicability of time-correlated single photon counting multiphoton microscopy to the spatiotemporal localisation of protein-protein interactions in situ. An Example of a new fluorescent protein variant with enhanced properties are given and the development of a FRET biosensor for simultaneous measurement of multiple intra-and inter-molecular interactions is illustrated by experimental evidence of an energy transfer cascade via multiple acceptors. The juxtaposition of interacting population and FRET efficiency is elucidated, with a priori knowledge, by multi-exponential analysis.
Coordination of protrusive and contractile cell±matrix contacts is important for cell adhesion an... more Coordination of protrusive and contractile cell±matrix contacts is important for cell adhesion and migration, but the mechanisms involved are not well understood. We report an unexpected direct association between fascin, an actin-bundling component of ®lopodia, microspikes and lamellipodial ribs, and protein kinase Ca (PKCa), a regulator of focal adhesions. The association is detectable by protein±protein binding in vitro, by coimmunoprecipitation from cell extracts, and in live cells as¯uorescence resonance energy transfer detected by¯uorescence imaging lifetime microscopy. The interaction is physiologically regulated by the extracellular matrix context of cells, depends on activation of PKCa and is mediated by the C1B domain of PKCa. Strikingly, a fascin mutant, fascin S39D, associates constitutively with PKCa. Through use of a newly developed set of membranepermeable peptides that separately inhibit either fascin/PKCa or fascin/actin binding, we have uncovered that speci®c blockade of the fascin/PKCa interaction increases cell migration on ®bronectin in conjunction with increased fascin protrusions and remodeling of focal adhesions. These results identify the fascin±PKCa interaction as an important novel intersection in the regulation and networking of cell± matrix contacts.
The multifunctional roles of BRCA1 include its ability to regulate transcriptional processes that... more The multifunctional roles of BRCA1 include its ability to regulate transcriptional processes that control differentiation at multiple levels, as well as functioning as a tumor suppressor. Data herein demonstrate that germline mutations in Brca1 impair luminal cell lineage and mammary development, with its deficiency converting ER-positive luminal tumors into basal-like cancers. Heterozygous mutations in Brca1 lead to downregulation of a number of luminal differentiation genes, explaining how it suppresses basal-like tumors, also highlighting its importance outside of its known highly publicized role in DNA repair.
Background Inferring molecular pathway activity is an important step towards reducing the complex... more Background Inferring molecular pathway activity is an important step towards reducing the complexity of genomic data, understanding the heterogeneity in clinical outcome, and obtaining molecular correlates of cancer imaging traits. Increasingly, approaches towards pathway activity inference combine molecular profiles (e.g gene or protein expression) with independent and highly curated structural interaction data (e.g protein interaction networks) or more generally with prior knowledge pathway databases. However, it is unclear how best to use the pathway knowledge information in the context of molecular profiles of any given study. Results We present an algorithm called DART (Denoising Algorithm based on Relevance network Topology) which filters out noise before estimating pathway activity. Using simulated and real multidimensional cancer genomic data and by comparing DART to other algorithms which do not assess the relevance of the prior pathway information, we here demonstrate that...
Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR ... more Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN-mutant background. However, in patients with a PTEN wild-type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy, and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer CWR22/22RV1 cells upregulate expression of the proteins PSMA, mGluR1, and the tyrosine kinase rece...
Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lu... more Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells...
European Journal of Nuclear Medicine and Molecular Imaging
The authors regret that they missed to indicate the middle initial of Dr. Ashley M. Groves in the... more The authors regret that they missed to indicate the middle initial of Dr. Ashley M. Groves in the original article. It has now been indicated. The original article has been corrected. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
N.Anilkumar and M.Parsons contributed equally to this work Coordination of protrusive and contrac... more N.Anilkumar and M.Parsons contributed equally to this work Coordination of protrusive and contractile cell±matrix contacts is important for cell adhesion and migration, but the mechanisms involved are not well understood. We report an unexpected direct association between fascin, an actin-bundling component of ®lopodia, microspikes and lamellipodial ribs, and protein kinase Ca (PKCa), a regulator of focal adhesions. The association is detectable by protein±protein binding in vitro, by coimmunoprecipitation from cell extracts, and in live cells as ¯uorescence resonance energy transfer detected by ¯uorescence imaging lifetime microscopy. The interaction is physiologically regu-lated by the extracellular matrix context of cells, depends on activation of PKCa and is mediated by the C1B domain of PKCa. Strikingly, a fascin mutant, fascin S39D, associates constitutively with PKCa. Through use of a newly developed set of membrane-permeable peptides that separately inhibit either fascin/PKC...
Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in ... more Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in vivo is difficult to achieve. The goal was to develop a new highly sensitive and reliable preclinical longitudinal in vivo imaging model for this purpose, thereby facilitating discovery and validation of anticancer therapies or molecular imaging agents. Methods: The strategy is based on breast cancer cells stably expressing the human sodium iodide symporter (NIS) fused to a red fluorescent protein, thereby permit-ting radionuclide and fluorescence imaging. Using whole-body nanoSPECT/CT with 99mTcO4−, we followed primary tumor growth and spontaneous metastasis in the presence or absence of etoposide treatment. NIS imaging was used to classify organs as small as in-dividual lymph nodes (LNs) to be positive or negative for metastasis, and results were confirmed by confocal fluorescence microscopy. Etoposide treatment efficacy was proven by ex vivo anticaspase
To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biol... more To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biologically relevant information from routine PET/MRI acquisitions for colorectal cancer (CRC) patients. Thirty consecutive primary CRC patients (mean age 63.9, range 42–83 years) prospectively underwent FDG-PET/MRI. FWC tumor parametric images generated from Dixon MR sequences underwent TA using commercially available research software (TexRAD). Data analysis comprised (1) identification of functional imaging correlates for texture features (TF) with low inter-observer variability (intraclass correlation coefficient: ICC > 0.75), (2) evaluation of prognostic performance for FWC-TF, and (3) correlation of prognostic imaging signatures with gene mutation (GM) profile. Of 32 FWC-TF with ICC > 0.75, 18 correlated with total lesion glycolysis (TLG, highest: rs = −0.547, p = 0.002). Using optimized cut-off values, five MR FWC-TF identified a good prognostic group with zero mortality (lowes...
European Journal of Nuclear Medicine and Molecular Imaging
Purpose This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose ... more Purpose This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)–Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. Methods This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. Results A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon – high Total Lesion Glycolysis (TLG) wit...
Objectives: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaini... more Objectives: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. Methods: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. Results: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI score...
Simple Summary There is a need to demonstrate additional clinical value/utility for PET/MRI in on... more Simple Summary There is a need to demonstrate additional clinical value/utility for PET/MRI in oncology which moves beyond simple diagnosis. We believe that our currently submitted work represents an initial step in realizing the goal of moving PET/MRI beyond simple diagnosis. We report how texture analysis of parametric images depicting tumor fractional water content derived from routine PET/MRI Dixon acquisitions shows good inter-operator agreement, generates biologically relevant information related to total lesion glycolysis and gene mutation count, and provides prognostic information that can potentially unlock new clinical applications for patients with colorectal cancer. This research study resulted from a long-standing multi-disciplinary collaboration between the nuclear medicine physicians at our institute and experts in quantitative imaging, MRI radiology, GI histology, clinical oncology in colorectal cancer, and several gastrointestinal surgeons at various local hospitals...
The potential of optical proteomic technologies to individualize prognosis and guide rational tre... more The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients
Background Systemic cancer spread is preceded by the establishment of a permissive microenvironme... more Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming. Methods A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy. Results S100A8/A9 imaging reflected MDSC abunda...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, May 3, 2015
Loco-regional recurrence of breast cancer poses significant clinical problems due to frequent ino... more Loco-regional recurrence of breast cancer poses significant clinical problems due to frequent inoperability once the chest wall is involved. Early detection of recurrence by molecular imaging agents against therapeutically targetable receptors, such as c-Met, would be of potential benefit. The aim of this study was to assess [(18)F]AH113804,a peptide-based molecular imaging agent with high affinity for human c-Met, for the detection of early stage loco-regional recurrence in a human basal-like breast cancer model, HCC1954. HCC1954 tumor-bearing xenograft models were established, and [(18)F]AH113804 was administered. Distribution of radioactivity was determined via positron emission tomography (PET) at 60 min post radiotracer injection. PET and CT (computerized tomography) images were acquired 10 days after tumor inoculation, to establish baseline distribution and uptake, and then on selected days after surgical tumor resection. CT images and caliper were used to determine the tumor ...
Confocal, Multiphoton, and Nonlinear Microscopic Imaging, 2003
We demonstrate the applicability of time-correlated single photon counting multiphoton microscopy... more We demonstrate the applicability of time-correlated single photon counting multiphoton microscopy to the spatiotemporal localisation of protein-protein interactions in situ. An Example of a new fluorescent protein variant with enhanced properties are given and the development of a FRET biosensor for simultaneous measurement of multiple intra-and inter-molecular interactions is illustrated by experimental evidence of an energy transfer cascade via multiple acceptors. The juxtaposition of interacting population and FRET efficiency is elucidated, with a priori knowledge, by multi-exponential analysis.
Coordination of protrusive and contractile cell±matrix contacts is important for cell adhesion an... more Coordination of protrusive and contractile cell±matrix contacts is important for cell adhesion and migration, but the mechanisms involved are not well understood. We report an unexpected direct association between fascin, an actin-bundling component of ®lopodia, microspikes and lamellipodial ribs, and protein kinase Ca (PKCa), a regulator of focal adhesions. The association is detectable by protein±protein binding in vitro, by coimmunoprecipitation from cell extracts, and in live cells as¯uorescence resonance energy transfer detected by¯uorescence imaging lifetime microscopy. The interaction is physiologically regulated by the extracellular matrix context of cells, depends on activation of PKCa and is mediated by the C1B domain of PKCa. Strikingly, a fascin mutant, fascin S39D, associates constitutively with PKCa. Through use of a newly developed set of membranepermeable peptides that separately inhibit either fascin/PKCa or fascin/actin binding, we have uncovered that speci®c blockade of the fascin/PKCa interaction increases cell migration on ®bronectin in conjunction with increased fascin protrusions and remodeling of focal adhesions. These results identify the fascin±PKCa interaction as an important novel intersection in the regulation and networking of cell± matrix contacts.
The multifunctional roles of BRCA1 include its ability to regulate transcriptional processes that... more The multifunctional roles of BRCA1 include its ability to regulate transcriptional processes that control differentiation at multiple levels, as well as functioning as a tumor suppressor. Data herein demonstrate that germline mutations in Brca1 impair luminal cell lineage and mammary development, with its deficiency converting ER-positive luminal tumors into basal-like cancers. Heterozygous mutations in Brca1 lead to downregulation of a number of luminal differentiation genes, explaining how it suppresses basal-like tumors, also highlighting its importance outside of its known highly publicized role in DNA repair.
Background Inferring molecular pathway activity is an important step towards reducing the complex... more Background Inferring molecular pathway activity is an important step towards reducing the complexity of genomic data, understanding the heterogeneity in clinical outcome, and obtaining molecular correlates of cancer imaging traits. Increasingly, approaches towards pathway activity inference combine molecular profiles (e.g gene or protein expression) with independent and highly curated structural interaction data (e.g protein interaction networks) or more generally with prior knowledge pathway databases. However, it is unclear how best to use the pathway knowledge information in the context of molecular profiles of any given study. Results We present an algorithm called DART (Denoising Algorithm based on Relevance network Topology) which filters out noise before estimating pathway activity. Using simulated and real multidimensional cancer genomic data and by comparing DART to other algorithms which do not assess the relevance of the prior pathway information, we here demonstrate that...
Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR ... more Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN-mutant background. However, in patients with a PTEN wild-type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy, and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer CWR22/22RV1 cells upregulate expression of the proteins PSMA, mGluR1, and the tyrosine kinase rece...
Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lu... more Over the past decade, immunotherapy delivered novel treatments for many cancer types. However, lung cancer still leads cancer mortality, and non-small-cell lung carcinoma patients with mutant EGFR cannot benefit from checkpoint inhibitors due to toxicity, relying only on palliative chemotherapy and the third-generation tyrosine kinase inhibitor (TKI) osimertinib. This new drug extends lifespan by 9-months vs. second-generation TKIs, but unfortunately, cancers relapse due to resistance mechanisms and the lack of antitumor immune responses. Here we explored the combination of osimertinib with anti-HER3 monoclonal antibodies and observed that the immune system contributed to eliminate tumor cells in mice and co-culture experiments using bone marrow-derived macrophages and human PBMCs. Osimertinib led to apoptosis of tumors but simultaneously, it triggered inositol-requiring-enzyme (IRE1α)-dependent HER3 upregulation, increased macrophage infiltration, and activated cGAS in cancer cells...
European Journal of Nuclear Medicine and Molecular Imaging
The authors regret that they missed to indicate the middle initial of Dr. Ashley M. Groves in the... more The authors regret that they missed to indicate the middle initial of Dr. Ashley M. Groves in the original article. It has now been indicated. The original article has been corrected. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
N.Anilkumar and M.Parsons contributed equally to this work Coordination of protrusive and contrac... more N.Anilkumar and M.Parsons contributed equally to this work Coordination of protrusive and contractile cell±matrix contacts is important for cell adhesion and migration, but the mechanisms involved are not well understood. We report an unexpected direct association between fascin, an actin-bundling component of ®lopodia, microspikes and lamellipodial ribs, and protein kinase Ca (PKCa), a regulator of focal adhesions. The association is detectable by protein±protein binding in vitro, by coimmunoprecipitation from cell extracts, and in live cells as ¯uorescence resonance energy transfer detected by ¯uorescence imaging lifetime microscopy. The interaction is physiologically regu-lated by the extracellular matrix context of cells, depends on activation of PKCa and is mediated by the C1B domain of PKCa. Strikingly, a fascin mutant, fascin S39D, associates constitutively with PKCa. Through use of a newly developed set of membrane-permeable peptides that separately inhibit either fascin/PKC...
Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in ... more Imaging spontaneous cancer cell metastasis or heterogeneous tumor responses to drug treatment in vivo is difficult to achieve. The goal was to develop a new highly sensitive and reliable preclinical longitudinal in vivo imaging model for this purpose, thereby facilitating discovery and validation of anticancer therapies or molecular imaging agents. Methods: The strategy is based on breast cancer cells stably expressing the human sodium iodide symporter (NIS) fused to a red fluorescent protein, thereby permit-ting radionuclide and fluorescence imaging. Using whole-body nanoSPECT/CT with 99mTcO4−, we followed primary tumor growth and spontaneous metastasis in the presence or absence of etoposide treatment. NIS imaging was used to classify organs as small as in-dividual lymph nodes (LNs) to be positive or negative for metastasis, and results were confirmed by confocal fluorescence microscopy. Etoposide treatment efficacy was proven by ex vivo anticaspase
To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biol... more To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biologically relevant information from routine PET/MRI acquisitions for colorectal cancer (CRC) patients. Thirty consecutive primary CRC patients (mean age 63.9, range 42–83 years) prospectively underwent FDG-PET/MRI. FWC tumor parametric images generated from Dixon MR sequences underwent TA using commercially available research software (TexRAD). Data analysis comprised (1) identification of functional imaging correlates for texture features (TF) with low inter-observer variability (intraclass correlation coefficient: ICC > 0.75), (2) evaluation of prognostic performance for FWC-TF, and (3) correlation of prognostic imaging signatures with gene mutation (GM) profile. Of 32 FWC-TF with ICC > 0.75, 18 correlated with total lesion glycolysis (TLG, highest: rs = −0.547, p = 0.002). Using optimized cut-off values, five MR FWC-TF identified a good prognostic group with zero mortality (lowes...
European Journal of Nuclear Medicine and Molecular Imaging
Purpose This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose ... more Purpose This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)–Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. Methods This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. Results A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon – high Total Lesion Glycolysis (TLG) wit...
Objectives: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaini... more Objectives: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. Methods: The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging–Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. Results: 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI score...
Simple Summary There is a need to demonstrate additional clinical value/utility for PET/MRI in on... more Simple Summary There is a need to demonstrate additional clinical value/utility for PET/MRI in oncology which moves beyond simple diagnosis. We believe that our currently submitted work represents an initial step in realizing the goal of moving PET/MRI beyond simple diagnosis. We report how texture analysis of parametric images depicting tumor fractional water content derived from routine PET/MRI Dixon acquisitions shows good inter-operator agreement, generates biologically relevant information related to total lesion glycolysis and gene mutation count, and provides prognostic information that can potentially unlock new clinical applications for patients with colorectal cancer. This research study resulted from a long-standing multi-disciplinary collaboration between the nuclear medicine physicians at our institute and experts in quantitative imaging, MRI radiology, GI histology, clinical oncology in colorectal cancer, and several gastrointestinal surgeons at various local hospitals...
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