Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
AI Summary:
This study demonstrates the feasibility of noninvasive molecular stratification using multiplex radiotracer PET. The results show that imaging signatures are influenced by genotype, tumor environment, and stage.AI Topics:
Purpose:
The current approach for molecular subtyping of colon cancer relies on gene expression profiling, which is invasive and has limited ability to reveal dynamics and spatial heterogeneity. Molecular imaging techniques, such as PET, present a noninvasive alternative for visualizing biological information from tumors. However, the factors influencing PET imaging phenotype, the suitable PET radiotracers for differentiating tumor subtypes, and the relationship between PET phenotypes and tumor genotype or gene expression–based subtyping remain unknown.
Experimental Design:
In this study, we conducted 126 PET scans using four different metabolic PET tracers, [18F]fluorodeoxy-D-glucose ([18F]FDG), O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET), 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT), and [11C]acetate ([11C]ACE), using a spectrum of five preclinical colon cancer models with varying genetics (BMT, AKPN, AK, AKPT, KPN), at three sites (subcutaneous, orthograft, autochthonous) and at two tumor stages (primary vs. metastatic).
Results:
The results demonstrate that imaging signatures are influenced by genotype, tumor environment, and stage. PET imaging signatures exhibited significant heterogeneity, with each cancer model displaying distinct radiotracer profiles. Oncogenic Kras and Apc loss showed the most distinctive imaging features, with [18F]FLT and [18F]FET being particularly effective, respectively. The tissue environment notably impacted [18F]FDG uptake, and in a metastatic model, [18F]FET demonstrated higher uptake.
Conclusions:
By examining factors contributing to PET-imaging phenotype, this study establishes the feasibility of noninvasive molecular stratification using multiplex radiotracer PET. It lays the foundation for further exploration of PET-based subtyping in human cancer, thereby facilitating noninvasive molecular diagnosis.
Malviya, Gaurav
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listLannagan, Tamsin R.M.
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
Nair, Reshmi and Lannagan, Tamsin R.M. and Jackstadt, Rene and Andrusaite, Anna and Cole, John and Boyne, Caitlin and Nibbs, Robert J.B. and Sansom, Owen J. and Milling, Simon (2024) Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance. OncoImmunology, 13 (1): 2330194. ISSN 2162-4011
Fetit, Rana and McLaren, Alistair S. and White, Mark and Mills, Megan L. and Falconer, John and Cortes-Lavaud, Xabier and Gilroy, Kathryn and Lannagan, Tamsin R.M. and Ridgway, Rachel A. and Nixon, Colin and Naiker, Varushka and Njunge, Renee and Clarke, Cassie and Whyte, Declan and Kirschner, Kristina and Jackstadt, Rene and Norman, Jim and Carlin, Leo M. and Campbell, Andrew D. and Sansom, Owen J. and Steele, Colin W. (2024) Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Research Communications, 4 (2). pp. 588-606. ISSN 2767-9764
See full publications listJohnson, Emma
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listMackintosh, Agata
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listBielik, Robert
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listPeters, A.L.
Author
Mactier, Karen and Baxter, Mark and Peters, Adam and Fair, Katherine and Hannington, Laura and Robertson, James and Wood, Georgina and Sarwar, Asma and Bishr, Mai and Webb, Rebekah and Al-Zubaidi, Mohammed and Eastlake, Leonie and Lankester, Kate and McInerney, Samuel and Creedon, Helen and Stillie, Alison and Purshouse, Karin (2024) TOURISM study (Treatment Outcomes in UteRIne SarcoMa): a 10-year retrospective evaluation of practice in the UK. BMJ Open, 14 (12): e094838. ISSN 2044-6055
Peters, A.L. and Hall, P.S. and Jordan, L.B. and Soh, F.Y. and Hannington, L. and Makaranka, S. and Urquhart, G. and Vallet, M. and Cartwright, D. and Marashi, H. and Elsberger, B. (2024) Enhancing clinical decision support with genomic tools in breast cancer: a Scottish perspective. Breast, 75: 103728. ISSN 0960-9776
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listSoloviev, Dmitry
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listBrown, Gavin
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listJackstadt, Rene
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
Nair, Reshmi and Lannagan, Tamsin R.M. and Jackstadt, Rene and Andrusaite, Anna and Cole, John and Boyne, Caitlin and Nibbs, Robert J.B. and Sansom, Owen J. and Milling, Simon (2024) Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance. OncoImmunology, 13 (1): 2330194. ISSN 2162-4011
Pennel, Kathryn A.F. and Hatthakarnkul, Phimmada and Wood, Colin S. and Lian, Guang-Yu and Al-Badran, Sara and Quinn, Jean A. and Legrini, Assya and Inthagard, Jitwadee and Alexander, Peter G. and van Wyk, Hester and Kurniawan, Ahmad and Hashmi, Umar and Gillespie, Michael A. and Mills, Megan and Ammar, Aula and Hay, Jennifer and Andersen, Ditte and Nixon, Colin and Rebus, Selma and Chang, David K. and Kelly, Caroline and Harkin, Andrea and Graham, Janet and Church, David and Tomlinson, Ian and Saunders, Mark and Iveson, Tim and Lannagan, Tamsin R. M. and Jackstadt, Rene and Maka, Noori and Horgan, Paul G. and Roxburgh, Campbell S. D. and Sansom, Owen J. and McMillan, Donald C. and Steele, Colin W. and Jamieson, Nigel B. and Park, James H. and Roseweir, Antonia K. and Edwards, Joanne (2024) JAK/STAT3 represents a therapeutic target for colorectal cancer patients with stromal-rich tumors. Journal of Experimental and Clinical Cancer Research, 43: 64. ISSN 1756-9966
See full publications listNixon, Colin
Author
Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.
Pennel, Kathryn and Kurniawan, Ahmad and Al-Badran, Sara Samir Foad and Schubert Santana, Leonor and Quinn, Jean and Nixon, Colin and Hatthakarnkul, Phimmada and Maka, Noori and Roxburgh, Campbell and McMillan, Donald and Edwards, Joanne (2024) IL6 and IL6R as prognostic biomarkers in colorectal cancer. Biomolecules, 14 (12): 1629. ISSN 2218-273X
Churchhouse, Antonia M.D. and Billard, Caroline V. and Suzuki, Toshiyasu and Pohl, Sebastian O.G. and Donnelly, Kevin and Nixon, Colin and Arends, Mark J. and Din, Shahida and Kirkwood, Kathryn and Marques Junior, Jair and Von Kriegsheim, Alexander and Coffelt, Seth B. and Myant, Kevin B. (2024) Loss of DOCK2 potentiates Inflammatory Bowel Disease-associated colorectal cancer via immune dysfunction and IFNγ induction of IDO1 expression. Oncogene, 43 (42). pp. 3094-3107. ISSN 0950-9232
See full publications listGilroy, Kathryn
Author
Malla, Sudhir B. and Byrne, Ryan M. and Lafarge, Maxime W. and Corry, Shania M. and Fisher, Natalie C. and Tsantoulis, Petros K. and Mills, Megan L. and Ridgway, Rachel A. and Lannagan, Tamsin R. M. and Najumudeen, Arafath K. and Gilroy, Kathryn L. and Amirkhah, Raheleh and Maguire, Sarah L. and Mulholland, Eoghan J. and Belnoue-Davis, Hayley L. and Grassi, Elena and Viviani, Marco and Rogan, Emily and Redmond, Keara L. and Sakhnevych, Svetlana and McCooey, Aoife J. and Bull, Courtney and Hoey, Emily and Sinevici, Nicoleta and Hall, Holly and Ahmaderaghi, Baharak and Domingo, Enric and Blake, Andrew and Richman, Susan D. and Isella, Claudio and Miller, Crispin and Bertotti, Andrea and Trusolino, Livio and Loughrey, Maurice B. and Kerr, Emma M. and Tejpar, Sabine and S:CORT Consortium and Maughan, Timothy S. and Lawler, Mark and Campbell, Andrew D. and Leedham, Simon J. and Koelzer, Viktor H. and Sansom, Owen J. and Dunne, Philip D. (2024) Author Correction: Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer. Nature Genetics, 56 (6): 1321. ISSN 1061-4036
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
Fetit, Rana and McLaren, Alistair S. and White, Mark and Mills, Megan L. and Falconer, John and Cortes-Lavaud, Xabier and Gilroy, Kathryn and Lannagan, Tamsin R.M. and Ridgway, Rachel A. and Nixon, Colin and Naiker, Varushka and Njunge, Renee and Clarke, Cassie and Whyte, Declan and Kirschner, Kristina and Jackstadt, Rene and Norman, Jim and Carlin, Leo M. and Campbell, Andrew D. and Sansom, Owen J. and Steele, Colin W. (2024) Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Research Communications, 4 (2). pp. 588-606. ISSN 2767-9764
See full publications listCampbell, Andrew D.
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
Fetit, Rana and McLaren, Alistair S. and White, Mark and Mills, Megan L. and Falconer, John and Cortes-Lavaud, Xabier and Gilroy, Kathryn and Lannagan, Tamsin R.M. and Ridgway, Rachel A. and Nixon, Colin and Naiker, Varushka and Njunge, Renee and Clarke, Cassie and Whyte, Declan and Kirschner, Kristina and Jackstadt, Rene and Norman, Jim and Carlin, Leo M. and Campbell, Andrew D. and Sansom, Owen J. and Steele, Colin W. (2024) Characterising neutrophil subtypes in cancer using scRNA sequencing demonstrates the importance of IL-1β/CXCR2 axis in generation of metastasis specific neutrophils. Cancer Research Communications, 4 (2). pp. 588-606. ISSN 2767-9764
See full publications listSansom, Owen
Author
Lu, Yuting and Travnickova, Jana and Badonyi, Mihaly and Rambow, Florian and Coates, Andrea and Khan, Zaid and Marques, Jair and Murphy, Laura C. and Garcia-Martinez, Pablo and Marais, Richard and Louphrasitthiphol, Pakavarin and Chan, Alex H.Y. and Schofield, Christopher J. and von Kriegsheim, Alex and Marsh, Joseph A. and Pavet, Valeria and Sansom, Owen J. and Illingworth, Robert S. and Patton, E. Elizabeth (2024) ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma. Cell Reports, 43 (7): 114406. ISSN 2639-1856
Pereira, Brooke A. and Ritchie, Shona and Chambers, Cecilia R. and Gordon, Katie A. and Magenau, Astrid and Murphy, Kendelle J. and Nobis, Max and Tyma, Victoria M. and Liew, Ying Fei and Lucas, Morghan C. and Naeini, Marjan M. and Barkauskas, Deborah S. and Chacon-Fajardo, Diego and Howell, Anna E. and Parker, Amelia L. and Warren, Sean C. and Reed, Daniel A. and Lee, Victoria and Metcalf, Xanthe L. and Lee, Young Kyung and O'Regan, Luke P. and Zhu, Jessie and Trpceski, Michael and Fontaine, Angela R.M. and Stoehr, Janett and Rouet, Romain and Lin, Xufeng and Chitty, Jessica L. and Porazinski, Sean and Wu, Sunny Z. and Filipe, Elysse C. and Cadell, Antonia L. and Holliday, Holly and Yang, Jessica and Papanicolaou, Michael and Lyons, Ruth J. and Zaratzian, Anaiis and Tayao, Michael and Da Silva, Andrew and Vennin, Claire and Yin, Julia and Dew, Alysha B. and McMillan, Paul J. and Goldstein, Leonard D. and Deveson, Ira W. and Croucher, David R. and Samuel, Michael S. and Sim, Hao-Wen and Batten, Marcel and Chantrill, Lorraine and Grimmond, Sean M. and Gill, Anthony J. and Samra, Jaswinder and Evans, Thomas R. Jeffry and Sasaki, Takako and Phan, Tri G. and Swarbrick, Alexander and Sansom, Owen J. and Morton, Jennifer P. and Australian Pancreatic Cancer Matrix Atlas (APMA) and Australian Pancreatic Cancer Genome Initiative (APGI) and Pajic, Marina and Parker, Benjamin L. and Herrmann, David and Cox, Thomas R. and Timpson, Paul (2024) Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response. Science Advances, 10 (27): eadl1197. ISSN 2375-2548
Malla, Sudhir B. and Byrne, Ryan M. and Lafarge, Maxime W. and Corry, Shania M. and Fisher, Natalie C. and Tsantoulis, Petros K. and Mills, Megan L. and Ridgway, Rachel A. and Lannagan, Tamsin R. M. and Najumudeen, Arafath K. and Gilroy, Kathryn L. and Amirkhah, Raheleh and Maguire, Sarah L. and Mulholland, Eoghan J. and Belnoue-Davis, Hayley L. and Grassi, Elena and Viviani, Marco and Rogan, Emily and Redmond, Keara L. and Sakhnevych, Svetlana and McCooey, Aoife J. and Bull, Courtney and Hoey, Emily and Sinevici, Nicoleta and Hall, Holly and Ahmaderaghi, Baharak and Domingo, Enric and Blake, Andrew and Richman, Susan D. and Isella, Claudio and Miller, Crispin and Bertotti, Andrea and Trusolino, Livio and Loughrey, Maurice B. and Kerr, Emma M. and Tejpar, Sabine and S:CORT Consortium and Maughan, Timothy S. and Lawler, Mark and Campbell, Andrew D. and Leedham, Simon J. and Koelzer, Viktor H. and Sansom, Owen J. and Dunne, Philip D. (2024) Author Correction: Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer. Nature Genetics, 56 (6): 1321. ISSN 1061-4036
See full publications listLewis, David Y.
Author
Malviya, Gaurav and Lannagan, Tamsin R.M. and Johnson, Emma and Mackintosh, Agata and Bielik, Robert and Peters, Adam and Soloviev, Dmitry and Brown, Gavin and Jackstadt, Rene and Nixon, Colin and Gilroy, Kathryn and Campbell, Andrew and Sansom, Owen J. and Lewis, David Y. (2024) Noninvasive stratification of colon cancer by multiplex PET imaging. Clinical Cancer Research, 30 (8). pp. 1518-1529. ISSN 1078-0432
See full publications listAvailable under License Creative Commons Attribution.
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